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INTRODUCTION This study comprehensively assessed the association between eight metabolites of urinary nicotine and cognitive impairment. METHODS This cross-sectional study was based on the data of Shenzhen Aging Related Disorder Cohort (SADC), including 51 elderly community data variables such as demographic characteristics, neuropsychological assessment and environmental factors, from July 2017 to November 2018. Participant's cognitive function was assessed by Mini-Mental State Examination (MMSE) scale and urinary nicotine metabolite [including cotinine N-β-D-glucuronide (CotGluc), rac 4-hydroxy-4-(3-pyridyl) butanoic acid dicyclohexylamine salt (HyPyBut), trans-3'-hydroxy cotinine O-β-D-glucuronide (OHCotGluc), and cotinine (Cot), etc.] concentrations were measured by high-performance liquid chromatographytandem mass spectrometry (LC-MS/MS). Generalized linear models and restricted cubic spline models were used to explore the relationships between the urinary levels of nicotine metabolite and cognitive function. RESULTS A total of 296 individuals aged >60 years were included. Individuals in the third quartile of CotGluc had a 0.786 point (95% CI: -1.244 -- -0.329) decrease or in the highest quartile of OHCotGluc had a 0.804 point (95% CI: -1.330 -- -0.278) decreased in attention and calculation compared to those in the lowest quartile (all p for trend <0.05). Compared with those in the lowest quartile, individuals in the highest quartile of CotGluc, HyPyBut, OHCotGluc and Cot, respectively, corresponded to a 1.043 point (95% CI: -2.269-0.182), 1.101 points (95% CI: -2.391-0.188), 2.318 points (95% CI: -3.615 -- -1.020), and 1.460 points (95% CI: -2.726 -- -0.194) decreased in MMSE total score (all p for trend <0.05). A nonlinear dose-response relationship between urinary levels of CotGluc, HyPyBut, OHCotGluc or Cot and cognitive function (all overall p<0.05, non-linear p<0.05). Subgroup analysis showed that urinary levels of CotGluc, OHCotGluc or Cot were significantly negatively associated with cognitive function (all p for trend <0.05) among females and non-smokers. CONCLUSIONS The findings highlight the public health implications of environmental tobacco smoke exposure, and effective interventions need to be performed for vulnerable populations. [ABSTRACT FROM AUTHOR]

Objectives: The evidence of intra-arterial thrombectomy (IAT) in acute ischemic stroke with internal carotid artery (ICA) occlusion was less solid than with middle cerebral artery occlusion. In this study, we aimed to investigate the predictors of good functional outcome of acute ischemic stroke with ICA occlusion after IAT in order to identify which characteristics were more associated with good functional outcome. Methods: From June 2016 to November 2018, all subjects who received IAT for acute stroke in three hospitals were enrolled. Those who had angiographic evidence of arterial occlusion not at ICA were excluded. Presence of tandem lesions was also excluded. After review of images, subjects without available non-enhanced CT or multiphase CTA were also excluded. The modified Rankin Scale (mRS) was used to separate all subjects into good outcome (mRS: 0-2) and poor outcome (mRS: 3-6) groups. Statistical analysis was used to find between group differences, including epidemiological data, clinical characters, imaging results, and IAT results. Results: The final enrolled subjects were 32 cases. The median and interquartile range of age was 74.5 [16.5] years old and there were 15 men. As compared with the poor outcome group, significant differences in the good outcome group included younger age (p = 0.038), higher percentage of usage of antithrombotic agents (p = 0.019), higher percentage of good or intermediate collateral (p = 0.018), and good reperfusion result (p = 0.018). Conclusion: The benefit of IAT in acute ICA occlusion was stronger in patients with better collateral and the success of IAT was also a key to good clinical outcome. [ABSTRACT FROM AUTHOR]

BACKGROUND: Environmental cadmium, with a high average dietary intake, is a severe public health risk. However, the long-term health implications of environmental exposure to cadmium in different life stages remain unclear. OBJECTIVES: We investigated the effects of early exposure to cadmium, at an environmentally relevant dosage, on adult metabolism and the mechanism of action. METHODS: We established mouse models with low-dose cadmium (LDC) exposure in early life to examine the long-term metabolic consequences. Intestinal flora measurement by 16S rDNA sequencing, microbial ecological analyses, and fecal microbiota transplant was conducted to explore the potential underlying mechanisms. RESULTS: Early LDC exposure (100 nM) led to fat accumulation in adult male mice. Hepatic genes profiling revealed that fatty acid and lipid metabolic processes were elevated. Gut microbiota were perturbed by LDC to cause diversity reduction and compositional alteration. Time-series studies indicated that the gut flora at early-life stages, especially at 8 weeks, were vulnerable to LDC and that an alteration during this period could contribute to the adult adiposity, even if the microbiota recovered later. The importance of intestinal bacteria in LDC-induced fat accumulation was further confirmed through microbiota transplantation and removal experiments. Moreover, the metabolic effects of LDC were observed only in male, but not female, mice. CONCLUSIONS: An environmental dose of cadmium at early stages of life causes gut microbiota alterations, accelerates hepatic lipid metabolism, and leads to life-long metabolic consequences in a sex-dependent manner. These findings provide a better understanding of the health risk of cadmium in the environment. CITATION: Ba Q, Li M, Chen P, Huang C, Duan X, Lu L, Li J, Chu R, Xie D, Song H, Wu Y, Ying H, Jia X, Wang H. 2017. Sex-dependent effects of cadmium exposure in early life on gut microbiota and fat accumulation in mice. Environ Health Perspect 125:437-446; http://dx.doi. org/10.1289/EHP360 [ABSTRACT FROM AUTHOR]

Holistic medicine is an interdisciplinary field of study that integrates all types of biological information (protein, small molecules, tissues, organs, external environmental signals, etc.) to lead to predictive and actionable models for health care and disease treatment. Despite the global and integrative character of this discipline, a comprehensive picture of holistic medicine for the treatment of complex diseases is still lacking. In this study, we develop a novel systems pharmacology approach to dissect holistic medicine in treating cardiocerebrovascular diseases (CCDs) by TCM (traditional Chinese medicine). Firstly, by applying the TCM active ingredients screened out by a systems-ADME process, we explored and experimentalized the signed drug-target interactions for revealing the pharmacological actions of drugs at a molecule level. Then, at a/an tissue/organ level, the drug therapeutic mechanisms were further investigated by a target-organ location method. Finally, a translational integrating pathway approach was applied to extract the diseases-therapeutic modules for understanding the complex disease and its therapy at systems level. For the first time, the feature of the drug-target-pathway-organ-cooperations for treatment of multiple organ diseases in holistic medicine was revealed, facilitating the development of novel treatment paradigm for complex diseases in the future. [ABSTRACT FROM AUTHOR]