Postconditioning of sevoflurane and propofol is associated with mitochondrial permeability transition pore

Background: Sevoflurane and propofol are effective cardioprotective anaesthetic agents, though the cardioprotection of propofol has not been shown in humans. Their roles and underlying mechanisms in anesthetic postconditioning are unclear. Mitochondrial permeability transition pore (MPTP) opening is a major cause of ischemia-reperfusion injury. Here we investigated sevoflurane- and propofol-induced postconditioning and their relationship with MPTP. Methods: Isolated perfused rat hearts were exposed to 40 min of ischemia followed by 1 h of reperfusion. During the first 15 min of reperfusion, hearts were treated with either control buffer (CTRL group) or buffer containing 20 μmol/L atractyloside (ATR group), 3% (v/v) sevoflurane (SPC group), 50 μmol/L propofol (PPC group), or the combination of atractyloside with respective anesthetics (SPC+ATR and PPC+ATR groups). Infarct size was determined by dividing the total necrotic area of the left ventricle by the total left ventricular slice area (percent necrotic area). Results: Hearts treated with sevoflurane or propofol showed significantly better recovery of coronary flow, end-diastolic pressures, left ventricular developed pressure and derivatives compared with controls. Sevoflurane resulted in more protective alteration of hemodynamics at most time point of reperfusion than propofol. These improvements were paralleled with the reduction of lactate dehydrogenase release and the decrease of infarct size (SPC vs CTRL: (17.48±2.70)% vs (48.47±6.03)%, P<0.05; PPC vs CTRL: (35.60±2.10)% vs (48.47±6.03)%, P<0.05). SPC group had less infarct size than PPC group (SPC vs PPC: (17.48±2.70)% vs (35.60±2.10)%, P<0.05). Atractyloside coadministration attenuated or completely blocked the cardioprotective effect of postconditioning of sevoflurane and propofol. Conclusion: Postconditioning of sevoflurane and propofol has cardio-protective effect against ischemia-reperfusion injury of heart, which is associated with inhibition of MPTP opening. Compared to propofol, sevoflurane provides superior protection of functional recovery and infarct size.

Change of Inflammatory Factors in Patients with Acute Coronary Syndrome

Background： Acute coronary syndrome （ACS） is closely related to unstable plaques and secondary thrombosis. The inflammatory cells in plaques and their inflammatory products may be the cause for plaque instability and ruptures. The study aimed to disclose the changes of inflammatory factors including serum intracellular adhesion molecule-1（ICAM-1 ）, chitinase-3-like protein I （YKL-40）, and lipoprotein-associated phospholipase A2 （Lp-PLA2） in patients with ACS and its clinical significance. Methods： A total of 120 patients with coronary heart disease （CHD） were categorized into 2 groups： 69 with ACS and 51 with stable angina pectoris （SAP）： 20 patients with chest pain and normal angiography served as a control group. The 120 patients with CHD were categorized into single-vessel disease group, double-vessel disease group, and three-vessel disease group based on the number of coronary artery stenosis. The severity of coronary artery stenosis was quantified based on coronary angiography using Gensini score. They were further divided into mild CHD group with its Gensini score 〈26 （n = 36）, moderate CHD group with its Gensini score being 26-54 （n = 48） and severe CHD group with its Gensini score 〉54 （n = 36）. Serum levels of ICAM-1, YKL-40, and Lp-PLA2 of different groups were determined by enzyme-linked immunosorbent assay. Correlation between ICAM-1, YKL-40, Lp-PLA2, and Gensini score was analyzed. Results： The levels of serum inflammatory factors ICAM-1, YKL-40, and Lp-PLA2 were significantly higher in the ACS group than those in control group and SAP group （all P 〈 0.05）： and compared with control group, no significant difference was observed in terms of the serum ICAM-1, YKL-40, and Lp-PLA2 levels in the SAP group （P 〉 0.05）.The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, single-vessel disease group, double-vessel disease group, and three-vessel disease group （all P 〉 0.05）. The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, mild CHD group （Gensini score 〈26）, moderate CHD group （Gensini score 26-54）, and severe CHD group （Gensini score 〉54） （all P 〉 0.05）. Nonparametric Spearman correlation analysis showed that the levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not correlated with the Gensini score in CHD patients （r=0.093, r=-0.149, and r= -0.085, all P 〉 0.05; respectively）. Conclusions： The serum levels of ICAM-1, YKL-40, and Lp-PLA2 were correlated with different clinical types of CHD, but not well correlated the severity and extent of artery stenosis, suggesting that ICAM-1, YKL-40, and Lp-PLA2 rnight be involved in occurrence of instability of atherosclerotic plaque, and might reflect the severity of CHD mostly through reflecting the plaque stability.

Protection Effect of Exogenous Fibroblast Growth Factor 21 on the Kidney Injury in Vascular Calcification Rats

Background： Chronic kidney disease （CKD） is closely related to the cardiovascular events in vascular calcification （VC）. However, little has known about the characteristics of kidney injury caused by VC. Fibroblast growth factor 21 （FGF21 ） is an endocrine thctor, which takes part in various metabolic actions with the potential to alleviate metabolic disorder diseases, Even FGF21 has been regarded as a biomarker in CKD, the role of FGF21 in CKD remains unclear. Therefore, in this study, we evaluate the FGF21 on the kidney injury in VC rats. Methods： The male Sprague-Dawley rats were divided into three groups： （ 1 ） control group, （2） Vitamin D3 plus nicotine （VDN）-induced VC group, （3） FGF21-treated VDN group. After 4 weeks, the rats were killed and the blood was collected for serum creatinine, urea nitrogen, calcium, and phosphate measurement. Moreover, the renal tissues were homogenized for alkaline phosphatases （ALPs） activity and calcium content. The levels of FGF21 protein were measured by radioimmunoassay. The levels of β-Klotho and FGF receptor 1 （FGFR1） protein were measured by enzyme-linked immunosorbent assay （EL1SA）. The structural damage and calcifications in aortas were stained by Alizarin-red S. Moreover, the structure of kidney was observed by hematoxylin and eosin staining. Results： The renal lhnction impairment caused by VDN modeling was ameliorated by FGF21 treatment, inhibited the elevated serum creatinine and urea level by 20.5% （34.750 ± 4.334 pmol/L vs. 27.630± 2.387pamol/L） and 4.0% （7.038 ± 0.590 mmol/L vs. 6.763 ±0.374 mmol/L; P 〈 0.01 ）, respectively, together with the structural damages of glomerular atrophy and renal interstitial fibrosis. FGF21 treatment downregulated the ALP activity, calcium content in the kidney of VC rats by 42.1% （P 〈 0.01 ） and 11.7% （P 〈 0.05） as well as ameliorated the aortic injury and calcification as compared with VDN treatment alone group, indicating an ameliorative effect on VC. EL1SA assays showed that the expression of [3-Klotho, a component of FGF21 receptor system was increased in VDN-treated VC rats by 37.4% （6.588 ± 0.957 pg/mg vs. 9.054 ± 0.963 pg/mg; P 〈 0.01）, indicating an FGF2 l-resistant state. Moreover, FGF21 treatment downregulated the level of β-Klotho in renal tissue by 16.7% （9.054 ± 0.963 pg/mg vs. 7.544± 1.362 pg/mg, P 〈 0.05）. However, the level of FGFR1, the receptor of FGF21, kept unchanged under VDN and VDN plus FGF21 administration （0.191 ± 0.0376 rig/rag vs. 0.189 ± 0.032 ng/mg rs. 0.181± 0.034 mg/mg; P 〉 0.05）. Conclusions： In the present study, FGF21 was observed to ameliorate the kidney injury in VDN-induced VC rats. FGF21 might be a potential therapeutic factor in CKD by cutting offthe vicious circle between VC and kidney injury.

Nine-hole Peg Test and Ten-meter Walk Test for Evaluating Functional Loss in Chinese Charcot-Marie-Tooth Disease

Background：The 9-hole peg test （9-HPT） and 10-meter walk test （10-MWT） are commonly used to test finger motor function and walking ability.The aim of this present study was to investigate the efficacy of these tests for evaluating functional loss in Chinese Charcot-Marie-Tooth （CMT） disease.Methods：Thirty-four Chinese CMT patients （CMT group） from August 2015 to December 2016 were evaluated with 9-HPT,10-MWT,CMT disease examination score,overall neuropathy limitation scale （ONLS）,functional disability score,and Berg Balance Scale （BBS）.Thirty-five age-and gender-matched healthy controls （control group） were also included in the study.Student＇s nonpaired or paired t-test were performed to compare data between two independent or related groups,respectively.The Pearson test was used to examine the correlations between recorded parameters.Results：The mean 9-HPT completion time in the dominant hand of CMT patients was significantly slower than that in the healthy controls （29.60 ± 11.89 s vs.19.58 ± 3.45 s;t =-4.728,P 〈 0.001）.Women with CMT completed the 9-HPT significantly faster than men with CMT （dominant hand：24.74 ± 7.93 s vs.33.01 ± 13.14 s,t =2.097,P =0.044）.The gait speed of the average self-selected velocity and the average fast-velocity assessed using 10-MWT for CMT patients were significantly slower than those in the control group （1.03 ± 0.18 m/s vs.1.44 ± 0.17 m/s,t =9.333,P 〈 0.001;1.31 ± 0.30 m/s vs.1.91 ± 0.25 m/s,t =8.853,P 〈 0.00 1,respectively）.There was no difference in gait speed between men and women.Both 9-HPT and 10-MWT were significantly correlated with the ONLS,functional disability score,and BBS （P 〈 0.05 for all）.Conclusion：The 9-HPT and 10-MWT might be useful for functional assessment in Chinese patients with CMT.

Incipient plasticity and activation volume of dislocation nucleation for TiZrNbTaMo high-entropy alloys characterized by nanoindentation

With instrumented nanoindentation, incipient plasticity of two as-cast BCC TiZrNbTa and TiZrNbTaMo high-entropy alloys(HEAs) are investigated in terms of pop-in events during loading, to characterize the dislocation behavior in these solid-solution alloys. It is shown that the maximum shear stress (max)required for dislocation nucleation is determined to be 1/16-1/12 and 1/18-1/14 of shear modulus for the TiZrNbTa and TiZrNbTaMo HEAs, respectively, which is nearly comparative to the theoretical shear stress of these alloys. The activation volumes of dislocation nucleation the TiZrNbTa and TiZrNbTaMo HEAs are determined to be 1.2 b^3 for and 1.3 b^3, respectively, which is substantially irrespective of alloying with Mo. Furthermore, activation volumes of these two HEAs are on the order of cubic burger’s vector and only one-third of the value for TiZrHfNb HEA, suggesting that a heterogeneous nucleation of dislocation took place in a way of direct atom-vacancy exchange, rather than of the cooperative motion of several atoms. These findings reveal the unique feature in deformation of BCC solid-solution complex alloys.

Bulk Metallic Glasses: MRI Compatibility and Its Correlation with Magnetic Susceptibility

Several bulk metallic glasses （BMGs） were selected to in vitro assess their magnetic resonance imaging （MRI） compatibility with agarose gel as a phantom, in terms of the extent of susceptibility artifacts in magnetic resonance image. The investigated metals include the Au49Ags.sPd2.3Cu26.9Si16.3, Zr61Ti2Cu2sA112, Cu50.4Nis.0Ti31Zr13 and Ti47Cu38Zr7.5Fe2.5Sn2Si1Ag2, together with pure titanium （CP-Ti） and Co-28Cr-6Mo alloy （ASTM-F799） for comparison. The artifact extent in MR images was quantitatively characterized according to the total volume in reconstructed 3D images with a series of slices under acquisition by fast spin echo （FSE） sequence and gradient echo （GRE） sequence. As indicated, artifact severity of the BMGs is much less than that of the CoCrMo alloy. The AuAgPdCuSi BMG manifested the smallest arti- fact among the four BMGs, while the TiCuZrFeSnSiAg BMG is comparative to the CP-Ti. The MRI compatibility of BMGs is ranked as a sequence of the Au-, Zr-, Cu- and Ti-based alloys. Dependence of material mag- netic susceptibility on artifact extent is also the case of the BMGs, even though it does not follow a simple linear relationship within a range of △χv = 30-180 ppm. These findings are of interest to reveal that the BMGs are potentially applied in the fields associated with an interventional MRI for MRI-guided surgeries.