tramadol is an opioid used as an analgesic for treating moderate or severe pain. the long-term use of tramadol can induce several adverse effects. The toxicological mechanism of tramadol abuse is unclear. Metabolomics is a very useful method for investigating the toxicology of drug abuse. We investigated the impact of chronic tramadol administration on the cerebrum of mice, focusing on the metabolites after tramadol administration. The mice received 20 or 50 mg/kg body weight tramadol dissolved in physiological saline daily for 5 weeks via oral gavage. Compared with the control group, the low dose tramadol group showed seven potential biomarkers, including gamma-hydroxybutyric acid, succinate semialdehyde, and methylmalonic acid, which were either up-or down-regulated. Compared with the control group, the high dose tramadol group showed ten potential biomarkers, including gamma-hydroxybutyric acid, glutamine, and O-phosphorylethanolamine, which were either up-or down-regulated. the up-regulated gamma-hydroxybutyric acid and the downregulated succinate semialdehyde revealed that the neurotransmitter system was disrupted after tramadol abuse. Compared with the low dose tramadol group, there were twenty-nine potential biomarkers in the high dose tramadol group, mainly related to the pentose phosphate pathway and glycerophospholipid metabolism. In conclusion, metabolomics in the tramadol abuse group demonstrated that long-term tramadol abuse can result in oxidative damage, inflammation, and disruption of the GABA neurotransmitter system, which will help to elucidate the toxicology of tramadol abuse. Tramadol is an effective analgesic agent for the treatment of moderately severe pain 1. Tramadol is considered to exert analgesic effects by binding the μ-opioid receptors and modulating the noradrenergic, GABAergic and serotonergic systems 2, 3 , or by acting as a serotonin-norepinephrine (NE) reuptake inhibitor 4. Tramadol in clinical not only can be used in general surgery, obstetrics, pediatrics and the treatment of oral surgery, as well as a variety of acute postoperative pain, is also used to relieve chronic pain, such as cancer 5. Because its analgesic action time is longer;its analgesia intensity decreased slowly, it is a relatively ideal drug for chronic pain medication.Most common side effects of tramadol include nausea, vomiting, sweating, fatigue, sedation 6, 7 , and dry mouth 8. More severe side effects include angioedema, increased effect of anticoagulants, hypoglycemia 7, 9 and serotonin toxicity 8 .Tramadol was identified as a controlled substance in the USA and UK (schedule IV drug) in 2014 10, 11 , and is also a controlled psychotropic substance in China, as more young people are abusing it to obtain psychological satisfaction. Having a lower affinity for the μ-opioid receptor, Tramadol has shown to have a lower risk for addiction with chronic use when compared with other opiates e.g. morphine and oxycodone 9, 12. Thus, many studies on the risks of opioid abuse have excluded tramadol 12-14. Mohamed HM 4 ...

As an important energy generation device of the compressed air energy storage (CAES) system, the radial-inflow turbine with shrouded impeller is employed to avoid the leakage flow in the rotor, especially in the high-pressure stages. However, a lack of clarity in the leakage characteristics and their drivers still prevents a systematic approach to the efficient performance and proper design of the shrouded radial turbine. In the present work, the shroud cavity leakage of the shrouded radial turbine has been studied numerically. The physical quantity synergy is innovatively employed to research the internal flow field of the shroud cavity. It is found that the influence of high rotating speed on the seal leakage cannot be neglected, and the average reduced rate of seal leakage is found to be about 9.9% for the designed clearance. The leakage mass flow rate could be reduced by increasing the rotating speed or decreasing the seal clearance. The synergy angle is able to predict the flow resistance in shroud cavity very well. According to the volume-averaged synergy angle in the seal, the dimensionless seal clearance smaller than 1.5% in the shrouded radial turbine is recommended. Compared with the seal clearance in other high-pressure shrouded turbomachines, the current recommended clearance should be within a reasonable field.

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