To establish a rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of rivaroxaban, apixaban and edoxaban in rat plasma. The analytes and the internal standard (diazepam) were separated on an Acquity UPLC BEH C18 chromatography column (2.1 mm × 50 mm, 1.7 μm) using gradient elution with a mobile phase of acetonitrile and 0.1 % formic acid in water at a flow rate of 0.4 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode to monitor the precursor-to-product ion transitions of m/z 436.1 → 145.1 for rivaroxaban, m/z 460.0 → 443.1 for apixaban, m/z 548.2 → 366.1 for edoxaban and m/z 285.2 → 193.1 for diazepam (IS) using a positive electrospray ionization interface. The method was validated over a concentration range of 1.0-200 ng/mL for rivaroxaban, 1.0-100 ng/mL for apixaban and 1.0-500 ng/mL for edoxaban. Total time for each chromatograph was 3.5 min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations <10.5 % and the accuracy values ranged from -9.9 to 11.3 %. The method was successfully applied to a pharmacokinetic study of rivaroxaban, apixaban and edoxaban in rats.

Background The capacity of postural control is a key factor related to falling in older people, particularly in older women with low back pain (LBP). Cognitive involvement in postural control increases with age. However, most scholars have not considered different difficulty levels of cognitive loads when exploring the effects of cognition on postural control in older patients with LBP. The present study is to investigate how different levels of cognitive loads modulate postural control in older women with LBP. Methods This was a cross-sectional study. Twenty older women with LBP were recruited into the LBP group, and 20 healthy older women without the history of LBP were recruited into the healthy control group. Balance parameters were computed to quantify postural control. All participants underwent the balance test, which required the participant to maintain stability during standing on a force platform with or without a concurrent cognitive task. The balance test included three levels of difficulties of posture tasks (eyes-open vs. eyes-closed vs. one-leg stance) and three cognitive tasks (without cognitive task vs. auditory arithmetic task vs. serial-7 s arithmetic task). Results A repeated-measure analysis of variance (3 postural tasks × 3 congnitive tasks× 2 groups) testing the effects of the different congnitive task levels on the performance in different postural conditions. Older women with LBP had worse postural control (as reflected by larger center of pressure (COP) parameters) than control group regardless of postural or cognitive difficulties. Compared with the single task, the COP parameters of participants with LBP were larger during dual tasks, even though the difficulty level of the cognitive task was low. Larger COP parameters were shown only if the difficulty level of the cognitive task was high in control group. Correlations between sway area/sway length and the number of falls were significant in dual tasks. Conclusion Our findings shed light on how cognitive loads modulate postural control for older women with LBP. Compared with control group, cognitive loads showed more disturbing effects on postural control in older women with LBP, which was associated with falling.

Recent evidence suggests that glutamate-induced cytotoxicity contributes to autophagic neuron death and is partially mediated by increased oxidative stress. Salidroside has been demonstrated to have neuroprotective effects in glutamate-induced neuronal damage. The precise mechanism of its regulatory role in neuronal autophagy is, however, poorly understood. This study aimed to probe the effects and mechanisms of salidroside in glutamate-induced autophagy activation in cultured rat cortical neurons. Cell viability assay, Western blotting, coimmunoprecipitation, and small interfering RNA were performed to analyze autophagy activities during glutamate-evoked oxidative injury. We found that salidroside protected neonatal neurons from glutamate-induced apoptotic cell death. Salidroside significantly attenuated the LC3-II/LC3-I ratio and expression of Beclin-1, but increased (SQSTM1)/p62 expression under glutamate exposure. Pretreatment with 3-methyladenine (3-MA), an autophagy inhibitor, decreased LC3-II/LC3-I ratio, attenuated glutamate-induced cell injury, and mimicked some of the protective effects of salidroside against glutamate-induced cell injury. Molecular analysis demonstrated that salidroside inhibited cortical neuron autophagy in response to glutamate exposure through p53 signaling by increasing the accumulation of cytoplasmic p53. Salidroside inhibited the glutamate-induced dissociation of the Bcl-2-Beclin-1 complex with minor affects on the PI3K/Akt/mTOR signaling pathways. These data demonstrate that the inhibition of autophagy could be responsible for the neuroprotective effects of salidroside on glutamate-induced neuronal injury.

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Aims/Introduction Diabetes has been considered as a ‘pro‐thrombotic state’ with enhanced platelet reactivity. Abnormality in platelet aggregation has been found in patients with its most common chronic complication – diabetic peripheral neuropathy (DPN). The purpose of this study was to investigate the potential association of platelet indices with nerve conduction function and the presence of DPN in Chinese patients with type 2 diabetes mellitus. Materials and Methods This study involved a total of 211 inpatients with type 2 diabetes mellitus and 55 healthy individuals for whom nerve conduction studies were carried out. DPN was diagnosed according to the American Diabetes Association recommendation. Clinical data were retrospectively collected. Results Patients with diabetes in whom neuropathy developed had lower levels of platelet count (PLT) and plateletcrit (PCT) than healthy controls (P < 0.05). Statistically significant associations of low PLT and PCT levels with the reduction of summed amplitude/velocity Z‐score, and the prolongation of F‐wave minimum latency in nerve conduction studies were found. Furthermore, after multivariate adjustment, logistic regression analysis showed that low levels of PLT (odds ratio 2.268, 95% confidence interval 1.072–4.797; P < 0.05; PLT <226 vs PLT ≥226) and PCT (odds ratio 2.050, 95% confidence interval 1.001–4.201; P < 0.05; PCT <0.222 vs PCT ≥0.222) in type 2 diabetes mellitus patients were risk factors for the presence of DPN. Conclusions Lower PLT and PCT levels are closely associated with poorer peripheral nerve conduction functions and the presence of neuropathy in patients with type 2 diabetes mellitus, which suggests that PLT and PCT might be potential biomarkers for showing DPN.