[Choice and application of time scale selection for Cox proportional hazards regression model in cohort studies].

Cox proportional hazards regression model (Cox model) is the most commonly used multivariate approach in time-to-event data analysis. A vital issue in fitting Cox model is choosing the appropriate time scale related to the occurrence of the outcome events. However, few domestic studies have focused on selecting and applying time scales for Cox model in the analysis of cohort study data. This study briefly introduced and compared several time scales in the reports from literature; and used data from the Shanghai Women's Health Study to illustrate the impact of different time scales on data analysis results, using the association between central obesity and the risk of liver cancer as an example. On this basis, several suggestions on selecting time scales in Cox model are proposed to provide a reference for the analysis of cohort study data.

A computational study of fatigue resistance of nitinol stents subjected to walk-induced femoropopliteal artery motion.

Fatigue resistance of nitinol stents implanted in femoropopliteal arteries is a critical issue because of their harsh biomechanical environment. Limb flexions due to daily walk expose the femoropopliteal arteries and, subsequently, the implanted stents to large cyclic deformations, which may lead to fatigue failure of the smart self-expandable stents. For the first time, this paper utilised the up-to-date measurements of walk-induced motion of a human femoropopliteal artery to investigate the fatigue behaviour of nitinol stent after implantation. The study was carried out by modelling the processes of angioplasty, stent crimping, self-expansion and deformation under diastolic-systolic blood pressure, repetitive bending, torsion and axial compression as well as their combination. The highest risk of fatigue failure of the nitinol stent occurs under a combined loading condition, with the bending contributing the most, followed by compression and torsion. The pulsatile blood pressure alone hardly causes any fatigue failure of the stent. The work is significant for understanding and improving the fatigue performance of nitinol stents through innovative design and procedural optimisation.

Patient-specific modelling of stent overlap: Lumen gain, tissue damage and in-stent restenosis.

This paper investigates the effects of multiple stents, with and without overlap, on the outcome of stent deployment in a patient-specific coronary artery using the finite element method. Specifically, the objective of this study is to reveal the effect of stent overlap on lumen gain, tissue damage and in-stent restenosis in percutaneous coronary intervention. Based on intravital optical coherency tomography imaging, three-dimensional model of a specific patient's coronary artery was developed, with two constituent layers (media and adventitia) and plaque, using Mimics. Hyperelastic models with damage, verified against experimental results, were used to describe stress-stretch responses of arterial layers and plaque. Abaqus CAE was used to create the models for Resolute Integrity™ drug-eluting stents and tri-folded expansion balloons. The results showed that lumen gain was improved by the overlapping stents than a single stent after deployment; however, damage to the media layer was greater, promoting a higher rate of in-stent restenosis. Meanwhile, the lumen gain achieved with the non-overlapping stents was smaller than that with the overlapping ones, due to an increased recoiling effect. Also, non-overlapping stents induced more tissue damage and higher rate of in-stent restenosis than overlapping stents. With respect to long-term clinical outcomes, the study recommended the use of a single stent where possible or multiple stents with minimal overlaps to treat long or angulated lesions.

Finite element evaluation of artery damage in deployment of polymeric stent with pre- and post-dilation.

Using finite element method, this paper evaluates damage in an arterial wall and plaque caused by percutaneous coronary intervention. Hyperelastic damage models, calibrated with experimental results, are used to describe stress-stretch responses of arterial layers and plaque; these models are capable to simulate softening behaviour of the tissue due to damage. Abaqus CAE is employed to create the finite element models for the artery wall (with media and adventitia layers), a symmetric uniform plaque, a bioresorbable polymeric stent and a tri-folded expansion balloon. The effect of percutaneous coronary intervention on vessel damage is investigated by simulating the processes of vessel pre-dilation, stent deployment and post-stenting dilation. Energy dissipation density is used to assess the extent of damage in the tissue. Softening of the plaque and the artery, due to the pre-dilation-induced damage, can facilitate the subsequent stent deployment process. The plaque and the artery experienced heterogeneous damage behaviour after the stent deployment, caused by non-uniform deformation. The post-stenting dilation was effective to achieve a full expansion of the stent, but caused additional damage to the artery. The continuous and discontinuous damage models yielded similar results in the percutaneous coronary intervention simulations, while the incorporation of plaque rupture affected the simulated outcomes of stent deployment. The computational evaluation of the artery damage can be potentially used to assess the risk of in-stent restenosis after percutaneous coronary intervention.

A Computational Study of Mechanical Performance of Bioresorbable Polymeric Stents with Design Variations.

PURPOSE: The study compared the mechanical behavior of bioresorbable polymeric stents with various designs during deployment, and investigated their fatigue performance under pulsatile blood pressure loading. METHODS: Finite element simulations have been carried out to compare the mechanical performance of four bioresorbable polymeric stents, i.e., Absorb, Elixir, Igaki-Tamai and RevaMedical, during deployment in diseased artery. Tri-folded balloon was modelled to expand the crimped stent onto the three-layered arterial wall with plaque. Cyclic diastolic-systolic pressure loading was applied to both stent and arterial wall to study fatigue behavior. RESULTS: Stents with larger U-bend and longer axial strut demonstrate more flexibility but suffer from severe dogboning and recoiling effects. Stress concentrations in the stent, as well as in the plaque and artery, are higher for stents designed with increased rigidity such as those with smaller U-bends and shorter axial struts. Simulations of fatigue deformation for Elixir stent demonstrate that the U-bends, with high stress concentrations, have a potential risk of fatigue failure under pulsatile systolic-diastolic blood pressure as opposed to the counter metallic stents which are normally free of fatigue failure. CONCLUSION: The structural behaviour of bioresorbable polymeric stent is strongly affected by its design, in terms of expansion, dogboning, recoiling and stress distribution during the deployment process.

Effect of fermented Ginkgo biloba leaves on nutrient utilisation, intestinal digestive function and antioxidant capacity in broilers.

1. A total of 648 one-day-old broiler chicks were randomly allocated into six equal groups to investigate the effect of diet supplemented with fermented Ginkgo biloba leaves (FGBL) at different levels on nutrient utilisation, intestinal digestive function and antioxidant activity. 2. Broilers in the six groups were offered basal diet supplemented with either 0, 1.5, 2.5, 3.5, 4.5 and 5.5 g/kg FGBL during the 42-d experiment, respectively. 3. Birds fed with 3.5 g/kg FGBL diet exhibited increased (P < 0.05) body weight gain, feed intake, apparent total tract retention (ATTR) of ether extract (EE) and relative weight of duodenum. Diets supplemented with FGBL increased (P < 0.05) antioxidant and digestive enzyme activities, and decreased malondialdehyde (MDA) concentrations at different degrees in pancreas and small intestine. The expression of antioxidant related genes was up-regulated (P < 0.05) by the transcription factor Nrf2 in small intestine, especially with supplementation of 3.5 and 4.5 g/kg FGBL in the diet. However, 5.5 g/kg diet significantly decreased (P < 0.05) feed conversion ratio and catalase activity (CAT) in the duodenum. 4. Body weight, relative weight of duodenum, amylase and trypsin activities in ileum, total antioxidant capacity (T-AOC) and CAT in duodenum, and glutathione peroxidase (GSH-PX) in ileum increased linearly and quadratically with FGBL content. Activities of amylase in pancreas, trypsin in jejunum, lipase in ileum, and GSH-PX in duodenum and jejunum increased linearly with FGBL content. Body weight gain, ATTR of EE, activities of trypsin in pancreas and amylase in jejunum, total superoxide dismutase activity in duodenum, T-AOC level and concentrations of MDA in the jejunum and ileum showed a quadratic (P < 0.05) dose response as supplemental FGBL level increased. 5. In conclusion, the addition of FGBL had the potential to improve nutrient utilisation, intestinal digestive function and antioxidant activity of broilers. The optimal dietary supplementation dose for broiler production seemed to be 3.5 to 4.5 g/kg.

A computational study of crimping and expansion of bioresorbable polymeric stents.

This paper studied the mechanical performance of four bioresorbable PLLA stents, i.e., Absorb, Elixir, Igaki-Tamai and RevaMedical, during crimping and expansion using the finite element method. Abaqus CAE was used to create the geometrical models for the four stents. A tri-folded balloon was created using NX software. For the stents, elastic-plastic behaviour was used, with hardening implemented by considering the increase of yield stress with the plastic strain. The tri-folded balloon was treated as linear elastic. To simulate the crimping of stents, a set of 12 rigid plates were generated around the stents with a radially enforced displacement. During crimping, the stents were compressed from a diameter of 3 mm to 1.2 mm, with the maximum stress developed at both inner and outer sides of the U-bends. During expansion, the stent inner diameter increased to 3 mm at the peak pressure and then recoiled to different final diameters after balloon deflation due to different stent designs. The maximum stress was found again at the U-bends of stents. Diameter change, recoiling effect and radial strength/stiffness were also compared for the four stents to assess the effect of design variation on stent performance. The effect of loading rate on stent deformation was also simulated by considering the time-dependent plastic behaviour of polymeric material.

A diffusion-based approach for modelling crack tip behaviour under fatigue-oxidation conditions.

Modelling of crack tip behaviour was carried out for a nickel-based superalloy subjected to high temperature fatigue in a vacuum and air. In a vacuum, crack growth was entirely due to mechanical deformation and thus it was sufficient to use accumulated plastic strain as a criterion. To study the strong effect of oxidation in air, a diffusion-based approach was applied to investigate the full interaction between fatigue and oxygen penetration at a crack tip. Penetration of oxygen into the crack tip induced a local compressive stress due to dilatation effect. An increase in stress intensity factor range or dwell times imposed at peak loads resulted in enhanced accumulation of oxygen at the crack tip. A crack growth criterion based on accumulated levels of oxygen and plastic strain at the crack tip was subsequently developed to predict the crack growth rate under fatigue-oxidation conditions. The predicted crack-growth behaviour compared well with experimental results.

Effect of two-year degradation on mechanical interaction between a bioresorbable scaffold and blood vessel.

This paper aims to evaluate the mechanical behaviour of a bioresorbable polymeric coronary scaffold using finite element method, focusing on scaffold-artery interaction during degradation and vessel remodelling. A series of nonlinear stress-strain responses was constructed to match the experimental measurement of radial stiffness and strength for polymeric scaffolds over 2-year in-vitro degradation times. Degradation process was modelled by incorporating the change of material property as a function of time. Vessel remodelling was realised by changing the size of artery-plaque system manually, according to the clinical data in literature. Over degradation times, stress on the scaffold tended to increase firstly and then decreased gradually, corresponding to the changing yield stress of the scaffold material; whereas the stress on the plaque and arterial layers showed a continuous decrease. In addition, stress reduction was also observed for scaffold, plaque and artery in the simulations with the consideration of vessel remodelling. For the first time, the work offered insights into mechanical interaction between a bioresorbable scaffold and blood vessel during two-year in-vitro degradation, which has significance in assisting with further development of bioresorbable implants for treating cardiovascular diseases.

Effect of supplemental fermented Ginkgo biloba leaves at different levels on growth performance, meat quality, and antioxidant status of breast and thigh muscles in broiler chickens.

The present study was conducted to investigate the influence of dietary supplementation with different levels of fermented Ginkgo biloba leaves (FGBL) on growth performance, slaughter performance, meat quality, antioxidant enzyme capacity, and free radical scavenging activities of muscles in broiler chickens. A total of 648 one-d-old broiler chickens were randomly allocated into six dietary treatments, including control group (CON group: basal diet), FGBL1, FGBL2, FGBL3, FGBL4, and FGBL5 groups (basal diet containing 1.5, 2.5, 3.5, 4.5, and 5.5 g/kg FGBL, respectively). Body weight gain and feed intake were recorded at 1, 21, and 42 d. At 42 d, 2 birds from each replicate were slaughtered. The results indicated that 3.5 g/kg FGBL diet significantly increased (P < 0.05) ADFI and ADG in 1 to 42 d and ADFI in 22 to 42 d compared with the CON group. In 1 to 21 d, 4.5 g/kg FGBL diet improved (P < 0.05) ADFI and ADG. With dietary FGBL increasing, the feed: gain ratio (F/G) in 1 to 21 d was significantly decreased (P < 0.05). However, birds fed with 5.5 g/kg FGBL had a higher (P < 0.05) F/G compared with other groups in 22 to 42 d and 1 to 42 d. In addition, FGBL3 and FGBL4 showed lower (P < 0.05) L* value in breast muscle, cooking loss in thigh muscle and lower 24 h and 48 h drip loss in both breast and thigh muscles than those of other groups. Furthermore, birds in the FGBL3 and FGBL4 groups increased (P < 0.05) the activity of total superoxide dismutase and total antioxidant capability in muscles, and the scavenging activities of 2,2΄-azino-bis (3-ethylbenzothiazoline-6-sulfonic) acid radical, OH•, and O2•- in thigh muscle, decreased (P < 0.05) malondialdehyde concentration in thigh muscle, as compared to the CON group. In conclusion, FGBL had the potential to improve the growth performance, meat quality and antioxidant status of broiler chickens. The optimal dose in the present study of FGBL in broiler diets was from 3.5 to 4.5 g/kg.

Computational analysis of mechanical stress-strain interaction of a bioresorbable scaffold with blood vessel.

Crimping and deployment of bioresorbable polymeric scaffold, Absorb, were modelled using a finite element method, in direct comparison with Co-Cr alloy drug eluting stent, Xience V. Absorb scaffold has an expansion rate lower than Xience V stent, with a less outer diameter achieved after balloon deflation. Due to the difference in design and material properties, Absorb also shows a higher recoiling than Xience V, which suggests that additional post-dilatation is required to achieve effective treatment for patients with calcified plaques and stiff vessels. However, Absorb scaffold induces significantly lower stresses on the artery-plaque system, which can be clinically beneficial. Eccentric plaque causes complications to stent deployment, especially non-uniform vessel expansion. Also the stress levels in the media and adventitia layers are considerably higher for the plaque with high eccentricity, for which the choice of stents, in terms of materials and designs, will be of paramount importance. Our results imply that the benefits of Absorb scaffolds are amplified in these cases.

A computational study of stent performance by considering vessel anisotropy and residual stresses.

Finite element simulations of stent deployment were carried out by considering the intrinsic anisotropic behaviour, described by a Holzapfel-Gasser-Ogden (HGO) hyperelastic anisotropic model, of individual artery layers. The model parameters were calibrated against the experimental stress-stretch responses in both circumferential and longitudinal directions. The results showed that stent expansion, system recoiling and stresses in the artery layers were greatly affected by vessel anisotropy. Following deployment, deformation of the stent was also modelled by applying relevant biomechanical forces, i.e. in-plane bending and radial compression, to the stent-artery system, for which the residual stresses generated during deployment were particularly accounted for. Residual stresses were found to have a significant influence on the deformation of the system, resulting in a re-distribution of stresses and a change of the system flexibility. The results were also utilised to interpret the mechanical performance of stent after deployment.

Fish consumption and all-cause mortality: a meta-analysis of cohort studies.

BACKGROUND/OBJECTIVES: Although fish consumption may have an influence on specific mortality of major chronic diseases, the relationship between fish consumption and all-cause mortality remains inconsistent. SUBJECTS/METHODS: We performed a systematic search of publications using PubMed and Web of science up to 31 December 2014. Summary relative risk (RR) for the highest versus lowest category of fish consumption on risk of all-cause mortality was calculated by using a random effects model. Potential nonlinear relation was tested by modeling fish intake using restricted cubic splines with three knots at fixed percentiles of the distribution. RESULTS: Twelve prospective cohort studies with 672,389 participants and 57,641 deaths were included in this meta-analysis. Compared with the lowest category, the highest category of fish intake was associated with about a 6% significantly lower risk of all-cause mortality (RR=0.94, 95% confidence interval (CI): 0.90, 0.98; I(2)=39.1%, P=0.06). The dose-response analysis indicated a nonlinear relationship between fish consumption and all-cause mortality. Compared with never consumers, consumption of 60 g of fish per day was associated with a 12% reduction (RR=0.88, 95% CI: 0.83, 0.93) in risk of total death. CONCLUSIONS: These results imply that fish consumption was associated with a reduced risk of all-cause mortality.

Effects of dietary supplementation with fermented ginkgo leaves on antioxidant capacity, intestinal morphology and microbial ecology in broiler chicks.

1. The purpose of this study was to evaluate the effects of supplementing diets with three types of fermented Ginkgo-leaves (FGL) on growth, antioxidant capacity, intestinal morphology and microbial ecology in broiler chicks. 2. A total of 300 d-old broilers were randomly allocated to 4 dietary treatments with 6 replications of 10 birds each. Birds were fed on basal diets (Control) or basal diets supplemented with 0.5% FGL with Candida utilis (CF group), Aspergillus niger (AF group) or their combined fermentation (CAF group), respectively, for a 42 d feeding trial. 3. AF and CAF supplementation improved body weight gain (BWG) (22-42 d) and feed conversion ratio (22-42 d and 1-42 d). Concentrations of serum α-tocopherol in CAF group, as well as hepatic α-tocopherol in the three FGL groups were increased, while hepatic reactive oxygen species (ROS) levels were greatly decreased in group AF and CAF. Chickens in AF and CAF groups had decreased hepatic protein carbonyls and malondialdehyde (MDA), as well as jejunal and ileal protein carbonyls. The total superoxide dismutase (T-SOD) activities and glutathione (GSH) of both jejunum and ileum of the CAF group were higher than the other groups. 4. Duodenal and jejunal villous height of birds fed on the AF and CAF diets were increased, while jejunal crypt depth (CD) was decreased. Furthermore, birds fed on AF and CAF supplemented diets had increased ileal lactobacilli populations. Decreased ileal and caecal Escherichia coli and Salmonellas populations was found for the birds fed on CAF supplemented diets. 5. The present study may indicate that the improved feed efficiency and intestinal functions in the group supplemented with AF and CAF are directly connected with the improved antioxidant capacity and intestinal microbial ecology.

Testicular hypofunction caused by activating p53 expression induced by reactive oxygen species in varicocele rats.

We investigated the mechanism of the testicular hypofunction induced by hypoxia in varicocele rats. Varicocele was induced by partial ligation of the left renal vein. Seven weeks later, left testis mass index was measured. The sperm counts and motility were tested by CASA. The change of seminiferous tubule tissue was observed by HE staining. The reactive oxygen species (ROS) level in left testicular tissue was measured by ELISA, and the expressions of HIF-1α and p53 were detected by immunohistochemistry and Western blot. The left testis mass index and the sperm motility were significantly lower in surgery group. By HE staining, the left seminiferous epithelial cell arrangement was incompact, disordered and vacuolated in surgery group. The ROS level in surgery group was significantly higher than the other groups. The results of immunohistochemistry and Western blot indicated that the expressions of HIF-1α and p53 increased significantly in surgery group. Our study demonstrated that varicocele caused hypoxia that could cause the rise of ROS level to induce the increase of p53 expression, leading to the decrease of testis mass index and changes of seminiferous tubules, which would reduce sperm motility and result in male infertility eventually.

Effects of material, coating, design and plaque composition on stent deployment inside a stenotic artery--finite element simulation.

Finite-element simulations have been carried out to study the effects of material choice, drug eluting coating and cell design on the mechanical behaviour of stents during deployment inside a stenotic artery. Metallic stents made of materials with lower yield stress and weaker strain hardening tend to experience higher deformation and stronger dogboning and recoiling, but less residual stresses. Drug eluting coatings have limited effect on stent expansion, recoiling, dogboning and residual stresses. Stent expansion is mainly controlled by the radial stiffness of the stent which is closely associated with the stent design. In particular, open-cell design tends to have easier expansion and higher recoiling than closed-cell design. Dogboning is stronger for slotted tube design and open-cell sinusoidal design, but reduced significantly for designs strengthened with longitudinal connective struts. After deployment, the maximum von Mises stress appears to locate at the U-bends of stent cell struts, with varying magnitude that depends on the materials and severity of plastic deformation. For the artery-plaque system, the stresses, especially in the plaque which is in direct contact with the stent, appear to be distinctly different for different stent designs and materials in terms of both distribution and magnitude. The plaque composition also strongly affects the expansion behaviour of the stent-artery system and modifies the stresses on the plaque.

Effect of feeding fermented Ginkgo biloba leaves on growth performance, meat quality, and lipid metabolism in broilers.

Aspergillus niger-fermented Ginkgo biloba leaves (FR) and its comparative effect with vitamin E (VE) and nonfermented (NF) Ginkgo leaves on growth, lipid metabolism, antioxidant capacity, and meat quality of broiler chicks were investigated. In total, 360 one-day-old broiler chicks were randomly allocated into 6 dietary treatments, which were then denoted as control group (basal diet), VE group (containing respectively 15 and 30 IU/kg of all-rac-α-tocopherol acetate in the starter and grower phase), NF group (containing respectively 0.35% and 0.7% NF in the starter and grower phase), and FR1, FR2, and FR3 groups containing respectively 0.2, 0.35, and 0.5% FR in the starter and 0.4, 0.7, and 1.0% FR in the grower phase. The results on performance showed that a significant (P < 0.05) reduction of feed:gain ratio of birds in the FR2 group (22-42 d and 1-42 d) was observed when compared with that of the control and NF groups. With dietary FR increasing, the serum α-tocopherol concentration increased linearly (P = 0.001). Compared with the control, broilers had higher (P < 0.05) serum high-density lipoprotein concentration, total superoxide dismutase activities, and total antioxidant capacity when they were provided with the FR2 and FR3 diet. Whereas the low-density lipoprotein and triglyceride concentrations were lower (P < 0.05 or P < 0.01) in broilers from FR2 or FR3 groups. As the dietary FR increased, abdominal fat (P = 0.002) and muscle malondialdehyde (P = 0.001) concentrations decreased. Furthermore, 24-h pH, 24-h drip loss, and cooking loss were greatly improved (P < 0.05) as the levels of FR increased. Birds fed with FR had a lower (P < 0.05) C16:0 and C18:0 concentrations but a greater (P = 0.001) concentration of C18:2, C18:3, and C20:4 than that of the control. In conclusion, FR can improve the growth performance and lipid metabolism of broilers with decreased abdominal fat deposition. Also, the antioxidant capacity and meat quality improving effects observed in broilers fed FR products might result from the increased retention of α-tocopherol and reduction in lipid peroxidation, as evidenced by the decrease in malondialdehyde and the increase in total superoxide dismutase activities.

Association of TSC gene variants and hypertension in Mongolian and Han populations.

We investigated a possible association between genetic variations in the thiazide-sensitive Na-Cl cotransporter (TSC) gene and essential hypertension (EH) in the Mongolian and Han ethnic groups in Inner Mongolia. Our study included 385 unrelated Mongolian herdsmen and 523 Han farmers. Nine tagSNPs of TSC were identified from the Chinese HapMap database based on pairwise r(2) ≥ 0.5 and minor allele frequency ≥0.05. Genotyping was performed using the PCR/ligase detection reaction assay. Association between tagSNPs and hypertension was investigated under the additive model. There were significant differences between the genotype and allele frequencies of rs13306673 between the EH group and the control group in the Han population. Significant associations were found between the rs7204044 variant and EH in both the Mongolian and Han ethnic groups. The frequency of haplotype GCA in the EH group was significantly higher than in the control group in the Mongolian population. In the Han population, the frequency of haplotype TGG was significantly higher in the EH group than in controls, whereas haplotype TGA occurred significantly less often in EH than in controls. We suggest that rs7204044 of TSC is a genetic factor for EH in these two ethnicities and that rs13306673 is a genetic factor for EH in the Han population.

[Studies on the construction and expression of recombinant human fusion gene Nm23-H1/HbFGF in Escherichia coli].

First, a piece of intermediate nucleic acid chain was designed according to the nucleic acid sequences of Nm23-H1 and HbFGF cDNA, then it was combined with the upstream primer of Nm23-H1 or the downstream primer of HbFGF to perform Polymerase Chain Reaction (PCR) respectively. The fusion gene Nm23-H1/HbFGF was constructed by four steps of PCR, and it was cloned into the plasmid vector pBV220. The recombinant was induced at 42 degrees C and analyzed by SDS-PAGE. Results show that the fusion gene Nm23-H1/HbFGF highly expresses its product in inclusion body in E. coli BL21(DE3). The expressing product is 14% of the total bacterial protein and it is 34 kD. ELISA assay and Western blot indicate that the inclusion body contains antigens of Nm23-H1 and HbFGF. By denaturation, renaturation and purification, the inclusion body was purified. Determination and biological activity assay show that the purified product contains two kinds of antigens which have biological activities of Nm23-H1 and HbFGF. All these data establish good base to study the tumor suppressor activity and oncogenicity of the fusion gene Nm23-H1/HbFGF in eukaryocyte.