A more accurate indicator to evaluate oxidative stress in rat plasma with osteoporosis.

Background: oxidative stress is linked to various human diseases which developed into the idea of "disrupted redox signaling". Osteoporosis (OP) is a chronic skeletal disorder characterized by low bone mineral density and deterioration of bone microarchitecture among which estrogen deficiency is the main cause. Lack of estrogen leads to the imbalance between oxidation and anti-oxidation in patients, and oxidative stress is an important link in the pathogenesis of OP. The ratio of the reduced to the oxidized thiols can characterize the redox status. However, few methods have been reported for the simultaneous determination of reduced forms and their oxidized forms of thiols in plasma. Methods: we developed a hollow fiber centrifugal ultrafiltration (HFCF-UF) method for sample preparation and validated a high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method to determine two reduced forms of thiols-homocysteine (Hcy), cysteine (Cys) levels and their respective oxidized compounds, homocystine (HHcy) and cystine (Cyss) in rat plasma simultaneously for the first time. Thirty-six female rats were randomly divided into three groups: normal control (NC), oxidative stress (ovariectomy, OVX) and ovariectomy with hydrogen-rich saline administration (OVX + HRS). Results: the validation parameters for the methodological results were within the acceptance criteria. There were both significant differences of Hcy/HHcy (Hcy reduced/oxidized) and Cys/Cyss (Cys reduced/oxidized) in rat plasma between three groups with both p < 0.05 and meanwhile, the p values of malondialdehyde, superoxide dismutase and glutathione peroxidase were all less than 0.01. The value of both Hcy/HHcy and Cys/Cyss were significantly decreased with the change of Micro-CT scan result of femoral neck in OVX group (both the trabecular thickness and trabecular number significantly decreased with a significant increase of trabecular separation) which demonstrate OP occurs. The change of Hcy/HHcy is more obvious and prominent than Cys/Cyss. Conclusions: the Hcy/HHcy and Cys/Cyss could be suitable biomarkers for oxidative stress and especially Hcy/HHcy is more sensitive. The developed method is simple and accurate. It can be easily applied in clinical research to further evaluate the oxidative stress indicator for disease risk factors.

Analysis of free concentrations of lamotrigine and active oxcarbazepine metabolite in clinical patients by hollow-fiber centrifugal ultrafiltration.

Aim: To establish a simple and accurate method to explore the correlation between free and total concentrations of lamotrigine (LTG) and the active oxcarbazepine metabolite monohydroxy derivative (MHD) (10,11-dihydro-10-hydroxycarbamazepine) in clinical patients. Materials & methods: Serum samples were prepared by hollow-fiber centrifugal ultrafiltration and then injected into UPLC for analysis. Results: Absolute recovery was as high as approximately 90.1-98.6% with excellent precision (relative standard deviation <6.7%). Analysis time was reduced to 5 min. There were significant individual differences in the protein binding rates of both LTG and MHD that were probably due to the use of different clinical patients. Conclusion: Free concentrations of LTG and MHD cannot be estimated by total concentration in specific clinical patients. Free drug monitoring of LTG and MHD in clinical therapeutic drug monitoring is important and essential.

Different Techniques of Minimally Invasive Craniopuncture for the Treatment of Hypertensive Intracerebral Hemorrhage.

OBJECTIVE: Efficacy of minimally invasive craniopuncture with the YL-1 puncture needle (hard-channel) and soft drainage tube (soft-channel) in treating hypertensive intracerebral hemorrhage (HICH). MATERIALS AND METHODS: A total of 150 patients with HICH were randomly assigned into 3 groups: conservative group (n = 50), hard-channel group (n = 50), and soft-channel group (n = 50). Computed tomography, National Institutes of Health Stroke Scale (NIHSS) and the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), and malondialdehyde (MDA) in serum and in drainage fluid were examined on days 2, 4, and 6 after operation. RESULTS: Compared with the conservative group, the serum levels of IL-6, TNF-α, and MDA were decreased and SOD was increased (P < 0.05); volumes of hematoma and perihematomal edema as well as NIHSS were reduced (P < 0.05) in minimally invasive groups on days 7, 14, and 28 after operation. Compared with the hard-channel group, the serum levels of IL-6, TNF-α, MDA, and SOD showed the same trend as above in the soft-channel group. In the soft-channel group, MDA was reduced and SOD was increased in brain drainage fluid on days 2, 4, and 6 (P < 0.05); volumes of hematoma and perihematomal edema on days 14 and 28 were found to be reduced compared with the hard-channel group (P < 0.05). There was no significant difference of volumes of hematoma and perihematomal edema on day 7 between minimally invasive groups. NIHSS of the soft-channel group appeared to be significantly reduced on days 7, 14, and 28 after operation (P < 0.05). CONCLUSIONS: Soft-channel minimally invasive craniopuncture is an ideal technique for treating HICH, with advantages of alleviating cerebral edema, reducing oxidative stress, and inhibiting inflammatory response.

Numerical research on the biomechanical behaviour of braided stents with different end shapes and stent-oesophagus interaction.

Quasi-static and dynamic numerical analyses are carried out by referring to computational models of commercial self-expandable braided stents with 3 commonly used end shapes, to evaluate the influence of different end shapes of stent on the biomechanical interaction between stent and oesophagus. The end shape has no influence on the equivalent stress, but has a great influence on the contact stress in the narrowest zone of the oesophagus-neoplasm system. However, the end shapes have significant effect on the equivalent stress and the contact stress in the healthy area of the oesophagus in contact with the stent ends. The results show that the maximum equivalent stress of the oesophagus occurs in the zone contact with the cup-shaped end and the maximum contact stress occurs in the zone contact with the edge of the trumpet-shaped stent end. Moreover, the stent apposition is almost not affected by the end shapes. Although small zones with an incomplete stent apposition appear in the transition zones of spherical-cup-shaped stent, such occurrence might not contribute to stent malapposition or stent migration. Therefore, these stents with 3 types of end shapes all have good stent apposition. Finally, the numerical simulation results can be used to assess the mechanical performance of stents with different end shapes, the effectiveness of stent expansion therapy, and the possibility of complications after stent implantation.

Effects of low oxygen dead space ventilation and breath-holding test in evaluating cerebrovascular reactivity: A comparative observation.

OBJECTIVE: This study aims to explore the application prospect of low oxygen dead space ventilation (LODSV) in evaluating vasomotor reactivity (VMR) by comparison between LODSV and breath-holding test (BHT). METHODS: Outpatient or inpatient patients who underwent transcranial Doppler sonography (TCD) were enrolled into this study. These patients successively underwent BHT and LODSV. The cooperation degree, tolerance conditions and adverse reactions in patients were recorded, and VMR was calculated, compared and analyzed. RESULTS: Patients had poor cooperation during BHT. Except for compensatory tachypnea after BHT, patients basically had no adverse reaction. The main manifestations of patients undergoing LODSV were deepened breathing and accelerated frequency in the end of the ventilation, and increased heart rate and a slight decline in pulse oxygen that rapidly recovered after ventilation. The increase rate of blood flow velocity in patients undergoing LODSV was significantly higher than in BHT (P<0.001), and its calculated VMR value was approximately 15% higher than BHT (P<0.001). BHT revealed a monophasic curve that slightly descends and rapidly increases, and LODSV revealed a curve that descends for a short time and slowly increases with a platform. CONCLUSION: LODSV can effectively eliminate the affect of poor cooperation in patients, and avoid intolerance caused by hypoxia. Hence, VMR value is more accurate than that determined by BHT; and this can reflect the maximum reaction ability of the blood vessels. Therefore, this method has higher clinical application value.

Numerical investigations of the mechanical properties of a braided non-vascular stent design using finite element method.

This paper discusses various issues relating to the mechanical properties of a braided non-vascular stent made of a Ni-Ti alloy. The design of the stent is a major factor which determines its reliability after implantation into a stenosed non-vascular cavity. This paper presents the effect of the main structural parameters on the mechanical properties of braided stents. A parametric analysis of a commercial stent model is developed using the commercial finite element code ANSYS. As a consequence of the analytical results that the pitch of wire has a greater effect than other structural parameters, a new design of a variable pitch stent is presented to improve mechanical properties of these braided stents. The effect of structural parameters on mechanical properties is compared for both stent models: constant and variable pitches. When the pitches of the left and right quarters of the stent are 50% larger and 100% larger than that of the central portion, respectively, the radial stiffness in the central portion increases by 10% and 38.8%, while the radial stiffness at the end portions decreases by 128% and 164.7%, the axial elongation by 25.6% and 56.6% and the bending deflection by 3.96% and 10.15%. It has been demonstrated by finite element analysis that the variable pitch stent can better meet the clinical requirements.

[Quantitative analysis of contents in compound fertilizer and application research using near infrared reflectance spectroscopy].

In the present study, a new approach to fast determining the content of urea, biuret and moisture in compound fertilizer composed of urea, ammonium dihydrogenphosphate and potassium chloride was proposed by using near infrared diffuse reflectance spectroscopy. After preprocessing the original spectrum, partial least squares (PLS) models of urea, biuret and moisture were built with the R2 values of 0.9861, 0.9770 and 0.9713 respectively, the root mean square errors of cross validation were 2.59, 0.38, 0.132 respectively. And the prediction correlation factors were 0.9733, 0.9215 and 0.9679 respectively. The authors detected six kinds of compound fertilizer in market for the model verification, the correlation factors were 0.9237, 0.9786 and 0.9874 respectively. The data implied that the new method can be used for situ quality control in the production process of compound fertilizer.

[Study on the axial strain sensor of birefringence photonic crystal fiber loop mirror based on the absolute integral of the monitoring peak].

In the present paper, the theoretical expression of the wavelength change and the axial strain of birefringence fiber loop mirror is developed. The theoretical result shows that the axial strain sensitivity of birefringence photonic crystal fiber loop mirror is much lower than conventional birefringence fiber loop mirror. It is difficult to measure the axial strain by monitoring the wavelength change of birefringence photonic crystal fiber loop mirror, and it is easy to cause the measurement error because the output spectrum is not perfectly smooth. The different strain spectrum of birefringence photonic crystal fiber loop mirror was measured experimentally by an optical spectrum analyzer. The measured spectrum was analysed. The results show that the absolute integral of the monitoring peak decreases with increasing strain and the absolute integral is linear versus strain. Based on the above results, it is proposed that the axial strain can be measured by monitoring the absolute integral of the monitoring peak in this paper. The absolute integral of the monitoring peak is a comprehensive index which can indicate the light intensity of different wavelength. This method of monitoring the absolute integral of the monitoring peak to measure the axial strain can not only overcome the difficulty of monitoring the wavelength change of birefringence photonic crystal fiber loop mirror, but also reduce the measurement error caused by the unsmooth output spectrum.

[Research on axial strain sensitivity of high-birefringence fiber loop mirror].

In the present paper, the theoretical expressions for the axial strain sensitivity of high-birefringence fiber loop mirror (Hi-Bi FLM) was developed. The key influence factors on the axial strain sensitivity are discussed for the same input light source as the high-birefringence fiber material is certain, including the high-birefringence fiber length and the sensing length. The relationship between the high-birefringence fiber material and the axial strain sensitivity is discussed for the same input light source. The results show that the wavelength shift of high-birefringence fiber loop mirror is linear with the axial strain, and the linear sensitivity is constant decided by the high-birefringence fiber material and the center wavelength of input light source, having nothing to do with the high-birefringence fiber length and the sensing length.

Harmonic oscillations in homeostatic controllers: Dynamics of the p53 regulatory system.

Homeostatic mechanisms are essential for the protection and adaptation of organisms in a changing and challenging environment. Previously, we have described molecular mechanisms that lead to robust homeostasis/adaptation under inflow or outflow perturbations. Here we report that harmonic oscillations occur in models of such homeostatic controllers and that a close relationship exists between the control of the p53/Mdm2 system and that of a homeostatic inflow controller. This homeostatic control model of the p53 system provides an explanation why large fluctuations in the amplitude of p53/Mdm2 oscillations may arise as part of the homeostatic regulation of p53 by Mdm2 under DNA-damaging conditions. In the presence of DNA damage p53 is upregulated, but is subject to a tight control by Mdm2 and other factors to avoid a premature apoptotic response of the cell at low DNA damage levels. One of the regulatory steps is the Mdm2-mediated degradation of p53 by the proteasome. Oscillations in the p53/Mdm2 system are considered to be part of a mechanism by which a cell decides between cell cycle arrest/DNA repair and apoptosis. In the homeostatic inflow control model, harmonic oscillations in p53/Mdm2 levels arise when the binding strength of p53 to degradation complexes increases. Due to the harmonic character of the oscillations rapid fluctuating noise can lead, as experimentally observed, to large variations in the amplitude of the oscillation but not in their period, a behavior which has been difficult to simulate by deterministic limit-cycle models. In conclusion, the oscillatory response of homeostatic controllers may provide new insights into the origin and role of oscillations observed in homeostatically controlled molecular networks.

The control of the controller: molecular mechanisms for robust perfect adaptation and temperature compensation.

Organisms have the property to adapt to a changing environment and keep certain components within a cell regulated at the same level (homeostasis). "Perfect adaptation" describes an organism's response to an external stepwise perturbation by regulating some of its variables/components precisely to their original preperturbation values. Numerous examples of perfect adaptation/homeostasis have been found, as for example, in bacterial chemotaxis, photoreceptor responses, MAP kinase activities, or in metal-ion homeostasis. Two concepts have evolved to explain how perfect adaptation may be understood: In one approach (robust perfect adaptation), the adaptation is a network property, which is mostly, but not entirely, independent of rate constant values; in the other approach (nonrobust perfect adaptation), a fine-tuning of rate constant values is needed. Here we identify two classes of robust molecular homeostatic mechanisms, which compensate for environmental variations in a controlled variable's inflow or outflow fluxes, and allow for the presence of robust temperature compensation. These two classes of homeostatic mechanisms arise due to the fact that concentrations must have positive values. We show that the concept of integral control (or integral feedback), which leads to robust homeostasis, is associated with a control species that has to work under zero-order flux conditions and does not necessarily require the presence of a physico-chemical feedback structure. There are interesting links between the two identified classes of homeostatic mechanisms and molecular mechanisms found in mammalian iron and calcium homeostasis, indicating that homeostatic mechanisms may underlie similar molecular control structures.