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Biomedical subjects

J Z Wu

Publications and source records attributed to J Z Wu.

At least 19 recordsLinked to original sources

The prevalence and treatment gap in epilepsy in China: an ILAE/IBE/WHO study.

The authors carried out a door-to-door survey to determine the prevalence of epilepsy among 55,000 people in China. The lifetime prevalence was 7.0/1000, and 41% of all persons had never received appropriate treatment. The prevalence of active epilepsy was 4.6/1000, and 63% of people with active epilepsy had not received antiepileptic treatment in the week before the survey. Figures for the prevalence and the treatment gap were significantly higher than previous estimates.

Anticonvulsants↗

Modeling of time-dependent force response of fingertip to dynamic loading.

An extended exposure to repeated loading on fingertip has been associated to many vascular, sensorineural, and musculoskeletal disorders in the fingers, such as carpal tunnel syndrome, hand-arm vibration syndrome, and flexor tenosynovitis. A better understanding of the pathomechanics of these sensorineural and vascular diseases in fingers requires a formulation of a biomechanical model of the fingertips and analyses to predict the mechanical responses of the soft tissues to dynamic loading. In the present study, a model based on finite element techniques has been developed to simulate the mechanical responses of the fingertips to dynamic loading. The proposed model is two-dimensional and incorporates the essential anatomical structures of a finger: skin, subcutaneous tissue, bone, and nail. The skin tissue is assumed to be hyperelastic and viscoelastic. The subcutaneous tissue was considered to be a nonlinear, biphasic material composed of a hyperelastic solid and an invicid fluid, while its hydraulic permeability was considered to be deformation dependent. Two series of numerical tests were performed using the proposed finger tip model to: (a) simulate the responses of the fingertip to repeated loading, where the contact plate was assumed to be fixed, and the bone within the fingertip was subjected to a prescribed sinusoidal displacement in vertical direction; (b) simulate the force response of the fingertip in a single keystroke, where the keyboard was composed of a hard plastic keycap, a rigid support block, and a nonlinear spring. The time-dependent behavior of the fingertip under dynamic loading was derived. The model predictions of the time-histories of force response of the fingertip and the phenomenon of fingertip separation from the contacting plate during cyclic loading agree well with the reported experimental observations.

Bone and Bones↗

How to determine the permeability for cement infiltration of osteoporotic cancellous bone.

Cement augmentation is an emerging surgical procedure in which bone cement is used to infiltrate and reinforce osteoporotic vertebrae. Although this infiltration procedure has been widely applied, it is performed empirically and little is known about the flow characteristics of cement during the injection process. We present a theoretical and experimental approach to investigate the intertrabecular bone permeability during the infiltration procedure. The cement permeability was considered to be dependent on time, bone porosity, and cement viscosity in our analysis. In order to determine the time-dependent permeability, ten cancellous bone cores were harvested from osteoporotic vertebrae, infiltrated with acrylic cement at a constant flow rate, and the pressure drop across the cores during the infiltration was measured. The viscosity dependence of the permeability was determined based on published experimental data. The theoretical model for the permeability as a function of bone porosity and time was then fit to the testing data. Our findings suggest that the intertrabecular bone permeability depends strongly on time. For instance, the initial permeability (60.89 mm(4)/N(*)s) reduced to approximately 63% of its original value within 18 seconds. This study is the first to analyze cement flow through osteoporotic bone. The theoretical and experimental models provided in this paper are generic. Thus, they can be used to systematically study and optimize the infiltration process for clinical practice.

Aged↗

Dynamic interaction between a fingerpad and a flat surface: experiments and analysis.

Many neural and vascular diseases in hands and fingers have been related to the degenerative responses of local neural and vascular systems in fingers to excessive dynamic loading. Since fingerpads serve as a coupling element between the hand and the objects, the investigation of the dynamic coupling between fingertip and subjects could provide important information for the understanding of the pathomechanics of these neural and vascular diseases. In the present study, the nonlinear and time-dependent force responses of fingertips during dynamic contact have been investigated experimentally and theoretically. Four subjects (2 male and 2 female) with an average age of 24 years participated in the study. The index fingers of right and left hands of each subject were compressed using a flat platen via a micro testing machine. A physical model was proposed to simulate the nonlinear and time-dependent force responses of fingertips during dynamic contact. Using a force relaxation test and a fast loading test at constant loading speed, the material/structural parameters underlying the proposed physical model could be identified. The predicted rate-dependent force/displacement curves and time-histories of force responses of fingertips were compared with those measured in the corresponding experiments. Our results suggest that the force responses of fingertips during the dynamic contacts are nonlinear and time-dependent. The physical model was verified to characterize the nonlinear, rate-dependent force-displacement behaviors, force relaxations, and time-histories of force responses of fingertips during dynamic contact.

Adult↗

Elastic anisotropy of articular cartilage is associated with the microstructures of collagen fibers and chondrocytes.

Chondrocyte shape and volumetric concentration change as a function of depth in articular cartilage. A given chondrocyte shape produces different effects on the global material properties depending on the structure of the collagen fiber network. The shape and volumetric concentration of chondrocytes in articular cartilage appear to be related to the mechanical stability of the matrix. The present study was aimed to investigate, theoretically, the effects of the structural arrangement of the collagen fiber network, and the shape and distribution of chondrocytes, on the global material behavior of articular cartilage. Articular cartilage was assumed to be a four-phasic composite comprised of a matrix (associated with the properties of the proteoglycan structure), vertically and horizontally distributed collagen fibers, and spheroidal inclusions representing chondrocytes. A solution for composite materials was used to estimate the global, effective material properties of cartilage. Only the elasticity of the solid phase was investigated in the present study. Our simulations suggest that a soft, spheroidal cell inclusion in a fiber-reinforced proteoglycan matrix affects the material properties differently depending on the shape of the spheroidal inclusions. If the long axis of the inclusions is parallel to the collagen fibers, as in the deep zone, the soft inclusions increase the stiffness of the composite in the fiber direction, and reduce the stiffness of the composite in the direction normal to the fibers. Furthermore, we found that Young's modulus normal to the contact surface increases from the superficial to the deep zone in articular cartilage by a factor of 10-50, a finding that agrees well with experimental observations. Our analysis suggests that the combination of proteoglycan matrix, fiber orientation, and shape of chondrocytes are intimately related and are likely adapted to optimize the mechanical stability and load carrying capacity of the structure.

Anisotropy↗

Inadequate placement of osteochondral plugs may induce abnormal stress-strain distributions in articular cartilage --finite element simulations.

The transplantation of osteochondral (cartilage-bone) plugs is an alternative approach to treat local, full thickness cartilage defects in young patients. It is technically difficult to control the amount of the press fit tolerance and the position of the osteochondral (OC) plug in the recipient hole. Inadequate placement of the OC plugs may produce abnormal stress and strain distributions within the cartilage, and thus influence the regeneration of the injured cartilage site and the maintenance of opposing, healthy cartilage surfaces. In the present study, the influence of press fit tolerance and the placement of the OC plug on the joint contact mechanics was simulated using finite element methods. The joint was assumed to be axi-symmetric with a spherical femur and tibia and a cylindrical OC plug. Our simulations showed that small misplacements of the OC plug induced abnormal tension in the articular cartilage of the opposing, healthy cartilage surface. Such tension might induce unpredictable adaptations, or possibly degenerations, in the opposing cartilage layer. The contact stress profiles in the joint were predicted to change discontinuously across the plug/recipient interface, even when the plug was perfectly placed in the recipient hole, i.e., the plug's surface was aligned with the recipient surface. For a fixed coefficient of friction and a fixed fit tolerance, the maximal sliding force was predicted to vary with the size of the plug and reached a maximum at a specific plug diameter. The present simulations should be helpful for the design of instruments for osteochondral transplantation and placement of OC plugs, for understanding articular cartilage adaptation following osteochondral repair, and for providing insight into the mechanics at the transplant/recipient interface where proper integration of the plug into the joint is most problematic.

Bone Transplantation↗

Simulation of mechanical responses of fingertip to dynamic loading.

Extended exposure to mechanical vibration has been related to many vascular, sensorineural and musculoskeletal disorders of the hand-arm system, frequently termed 'hand-arm vibration syndrome' (HAVS). A two-dimensional, nonlinear finite element model of a fingertip is developed to study the stress and strain fields of the soft tissue under dynamic loading, that may be encountered while grasping and operating a hand-held power tool. The model incorporates the most essential anatomical elements of a fingertip, such as soft tissue, bone, and nail. The finger is assumed to be in contact with a steel plate, simulating the interaction between the fingertip and a vibrating machine tool or handle. The soft tissue is assumed to be nonlinearly visco-elastic, while the nail, bone, and steel plate are considered to be linearly elastic. In order to study the time-dependent deformation behavior of the fingertip, the numerical simulations were performed under ramp-like loading with different ramping periods and sinusoidal vibrations of the contacting plate at three different frequencies (1, 10, and 31.5 Hz). Owing to relatively large deformations of the soft tissue under specified static and dynamic loading, Lagrangian large deformation theory was applied in the present analysis. The effects of the loading rate and the frequency of the sinusoidal vibration on the time-dependent strain/stress distributions in the different depth within the soft tissue of the fingertip are investigated numerically. Our simulations suggest that the soft tissue of the fingertip experiences high local stress and strain under dynamic loading and the fingertip may separate from the vibrating contact surface due to the viscous deformation behaviour of the soft tissue. For a given deformation, the high frequency loading produces a higher stress in the tissues compared to that obtained at a low frequency loading. The present model may serve as a useful tool to study the mechanism of tissue degeneration under vibratory loading encountered during operation of hand-held power tools.

Computer Simulation↗

Internally located signal peptides direct hepatitis C virus polyprotein processing in the ER membrane.

An endoplasmic reticulum (ER) signal peptide is an amino acid sequence motif that directs the translocation of nascent polypeptides to the lumen of ER membrane. Most of known ER signal peptides are either N-terminal cleavable or internally uncleavable. In the structural protein region of hepatitis C virus (HCV) polyprotein, however, four internally located cleavable signal peptides are arranged in a tandem array. The published experimental results indicated that the nascent HCV polyprotein is processed in the ER membrane by host signal peptidase(s) to the respective viral proteins. Here we propose that the four ER signal peptides lead the nascent HCV polyprotein to ER membrane, and the four internally located cleavable signal peptides are the sole determinant for the compartment localization of the matured viral proteins. After cleavage at the C-terminus, the signal peptides retain at the C-terminus of mature proteins, and serve as ER membrane anchors. The signal peptide directed polyprotein processing in the ER membrane preludes the virion assembly and budding from the ER membrane. This unique processing may be a general mechanism adopted by many types of virus for virion assembly and replication. The revelation of signal peptidase involved in HCV polyprotein processing presents a novel drug target to suppress HCV viral replication for the much needed HCV therapy.

Amino Acid Sequence↗

Dietary protective and risk factors for esophageal and stomach cancers in a low-epidemic area for stomach cancer in Jiangsu Province, China: comparison with those in a high-epidemic area.

Comparative epidemiological studies with ecological and case-control approaches in high- and low-epidemic areas of China have provided us with much evidence with regard to risk and benefit in the environment. To clarify how dietary factors are involved in esophageal and stomach cancer development, we performed a case-control study in a low-epidemic area, and compared the findings with those obtained earlier for a high-epidemic area for stomach cancer in the same Jiangsu Province, China. We recruited 199 and 187 cases with esophageal and stomach cancers, respectively, and 333 population-based common controls. Odds ratios (ORs) for esophageal and stomach cancers were calculated with adjustment for potential confounding factors, using an unconditional logistic model. Current and former smoking elevated the OR for esophageal cancer, along with high intake of pickled vegetables and broiled meat, while decreased ORs were observed for frequently consumed raw vegetables and garlic. With regard to stomach cancer, ORs were increased with frequent consumption of salty fish, leftover gruel, and broiled meat, and lowered by snap bean consumption. The present risk factors were common to the previously obtained results in the high-epidemic area, and similarly distributed in each general population. While more protective factors were observed in the high-epidemic area, their penetrance was much greater in the low-epidemic area. The present study thus suggests that frequent vegetable and garlic consumption contributes to low mortality rates for esophageal and stomach cancers in a low-epidemic area, counteracting similar exposure levels for risk factors as in the high-epidemic area.

Adult↗

The relationship between force depression following shortening and mechanical work in skeletal muscle.

Force depression following muscle shortening was investigated in cat soleus (n=6) at 37 degrees C for a variety of contractile conditions with the aim to test the hypotheses that force depression was independent of the speed of shortening and was directly related to the mechanical work produced by the muscle during shortening. Force depression was similar for tests in which the mechanical work performed by the muscle was similar, independent of the speed of shortening (range of speeds: 4-256mm/s). On the other hand, force depression varied significantly at a given speed of shortening but different amounts of mechanical work, supporting the hypothesis that force depression was not speed - but work dependent. The variations in the mechanical work produced by the muscle during shortening accounted for 87-96% of the variance observed in the force depression following shortening further supporting the idea that the single scalar variable work accounts for most of the observed loss in isometric force after shortening. The results of the present study are also in agreement with the notion that the mechanism underlying force depression might be associated with an inhibition of cross-bridge attachments in the overlap zone formed during the shortening phase, as proposed previously (Herzog and Leonard, 1997. Journal of Bimechanics 30 (9), 865-872; Maréchal and Plaghki, 1979.

Actin Cytoskeleton↗

Joint contact mechanics in the early stages of osteoarthritis.

Joint degeneration in the early stages of osteoarthritis (OA) may be reflected in changes in structural and material properties in articular cartilage. The aim of the present study was to simulate numerically the contact area and stress distribution in normal and "diseased" cartilage layers for dynamic loading. The initial stages of osteoarthritis were simulated based on an experimental model: the anterior cruciate ligament-transected cat knee. In this model, cartilage layers become thicker, softer, and more permeable than the corresponding healthy cartilage layers within weeks of intervention. In our numerical simulations, the diseased cartilage was modelled by changing the thickness, permeability, shear modulus, and Poisson's ratio of the cartilage in accordance with observations in this experimental model of osteoarthritis. The theoretical model of normal and diseased articular cartilage was based on a biphasic representation of cartilage, and the joint was assumed to be axi-symmetric. It was found that, for a given loading condition, the contact areas increase and peak stresses decrease in the diseased compared to the normal joint. According to our simulations, areas of normal joint contact become unloaded and areas of little or no contact become overloaded in the early stages of osteoarthritis compared to the situation in normal joints. Based on these results, we speculate that OA may be initiated following ACL transection because of an overloading of specific regions of the joint, either because of the altered contact mechanics or the disrupted joint stability, despite a general decrease in the contact pressure.

Animals↗

Structures of two diterpenoid dimers from bulbs of Fritillaria ebeiensis.

A new ent-kaurane diterpenoid dimer, fritillebinide C(1) together with one known diterpenoid dimer fritillebinide B (2) were isolated from the bulbs of Fritillaria ebeiensis G.D. Yu et G.Q. Ji. Compound 1 has been determined to be ent-3beta-acetoxy-kauran-16beta,17-acetal ent-16beta-kauran-17(S)-aldehyde(1) by means of spectral analysis and chemical evidence.

Chromatography↗

Structural elucidations of two ent-kaurane dimers from bulbs of Fritillaria ebeiensis var. purpurea.

A novel ent-kaurane diterpenoid dimer, fritillebinide B (1) together with one known diterpenoid dimer fritillebinide A (2) were isolated from the bulbs of Fritillaria eheiensis var. purpurea G.D. Yu et P. Li. Compound 1 has been established to be ent-3beta-acetoxy-kauran-16beta,17-acetal ent-16beta-kauran-17(R)-aldehyde (1) by means of spectral analysis and chemical evidence.

Chromatography↗

Interaction between oppositely charged micelles or globular proteins.

Monte Carlo simulations and the hypernetted chain theory are used to study the interaction between spherical macroions of opposite charge immersed in a solution of monovalent or divalent simple electrolyte. These calculations represent the first step toward studying phase behavior and precipitation kinetics in solutions containing a mixture of macroions with positive and negative net charges. The potential of mean force between colloidal particles is determined as a function of colloid-colloid separation. In addition to having an opposite sign, the calculated potential of mean force is found to be stronger and longer-ranged than observed in the case of equally charged macroparticles. The difference is more pronounced in the presence of divalent counterions and is especially noticeable when we compare distinct Coulombic and hard-core collision contributions to the interaction between equally and oppositely charged colloids. The present observations suggest the dominance of attractive forces between globally neutral but electrostatically heterogeneous macroparticles. While our numerical results cannot be successfully analyzed by existing theories, they provide useful guidance and benchmark data for the development of advanced analytic descriptions.

Chemical Precipitation↗

Finite element simulation of location- and time-dependent mechanical behavior of chondrocytes in unconfined compression tests.

Experimental evidence suggests that cells are extremely sensitive to their mechanical environment and react directly to mechanical stimuli. At present, it is technically difficult to measure fluid pressure, stress, and strain in cells, and to determine the time-dependent deformation of chondrocytes. For this reason, there are no data in the published literature that show the dynamic behavior of chondrocytes in articular cartilage. Similarly, the dynamic chondrocyte mechanics have not been calculated using theoretical models that account for the influence of cell volumetric fraction on cartilage mechanical properties. In the present investigation, the location- and time-dependent stress-strain state and fluid pressure distribution in chondrocytes in unconfined compression tests were simulated numerically using a finite element method. The technique involved two basic steps: first, cartilage was approximated as a macroscopically homogenized material and the mechanical behavior of cartilage was obtained using the homogenized model; second, the solution of the time-dependent displacements and fluid pressure fields of the homogenized model was used as the time-dependent boundary conditions for a microscopic submodel to obtain average location- and time-dependent mechanical behavior of cells. Cells and extracellular matrix were assumed to be biphasic materials composed of a fluid phase and a hyperelastic solid phase. The hydraulic permeability was assumed to be deformation dependent and the analysis was performed using a finite deformation approach. Numerical tests were made using configurations similar to those of experiments described in the literature. Our simulations show that the mechanical response of chondrocytes to cartilage loading depends on time, fluid boundary conditions, and the locations of the cells within the specimen. The present results are the first to suggest that chondrocyte deformation in a stress-relaxation type test may exceed the imposed system deformation by a factor of 3-4, that chondrocyte deformations are highly dynamic and do not reach a steady state within about 20 min of steady compression (in an unconfined test), and that cell deformations are very much location dependent.

Animals↗

DNA-liposome complexes transduction of herpes simplex virus thymidine kinase renders human tongue cancer cell line sensitive to ganciclovir in vitro.

OBJECTIVE: To evaluate, in vitro, the cytotoxicity of the herpes simplex virus thymidine kinase (HSV1-tk) gene and ganciclovir (GCV) treatment, a widely used prodrug/suicide gene therapy, in human tongue cancer cell line Tbp-TL. METHODS: Retrovirus expressing plasmid-liposome complex transduction was used. After treatment with G418 for 3 weeks, the integrated HSV1-tk gene was detected by PCR test with the primers specifically designed for HSV1-tk cDNA; HSV1-tk mRNA was detected with in situ hybridization method. In vitro cytotoxicity effect of HSV-GCV on Tbp-TL was detected with MTT and trypan blue exclusion test. RESULTS: In vitro experiments demonstrated dose- and time-dependent cell death by transduction of the HSV1-tk gene followed by GCV treatment. The IC50 (the concentration required to elicit 50% growth inhibition) shifted from 1000 micrograms/mL in non-transduced Tbp-TL cells to 1.1 micrograms/mL in Tbp-TL/TK cells transduced with HSV1-tk gene, with the therapeutic index of 1000. Treatment with GCV at a dose of 10 micrograms/mL for 5 days led to complete cell death in HSV1-tk transduced tumor cells. When mixed with tk positive cells, the non-transduced cells (both the parent Tbp-TL cells as well as another non-transduced cell, the human muco-epidermoid carcinoma cell line M3SP2) were also killed by a degree associated with the percentage of tk positive cells. Seventy to 90% of the mixed cells were killed with only 10% to 20% tk positive cells involved. CONCLUSION: These results suggest that the HSV-tk/GCV approach to human tongue cancer cell line may be efficacious, with a wide therapeutic range, and that it exerts a bystander effect in vitro.

Antineoplastic Agents↗