The effect of secukinumab treatment for psoriasis on serum cytokines and correlation with disease severity.

OBJECTIVE: To investigate the effects of secukinumab treatment for psoriasis on different functional cytokines and inflammatory mediators in patients' serum METHODS: Enzyme-linked immunosorbent assay was used to detect interleukin (IL)-1ß and IL-1RA associated with intrinsic immunity; IL-6, IL-18, and growth regulated oncogene alpha (GROα) associated with neutrophils; IL-12, tumour necrosis factor (TNF)-α, and interferon (IFN)-γ associated with Th1; IL-23, IL-17A, and IL-22 associated with Th17; Thymus activation regulated chemokine (TARC), IL-13, and defensin beta 2 (DEFB2) associated with Th2; Vascular endothelial growth factor (VEGF)-A and IL-10 associated with angiogenesis; and IFN-γ associated with sepsis in the peripheral blood of 12 patients with common psoriasis treated with secukinumab and 15 healthy controls. IL-23, IL-17A, IL-22 associated with Th17; TARC, IL-13, DEFB2 associated with Th2; VEGF-A, IL-10 associated with angiogenesis and procalcitonin (PCT) associated with sepsis. The differences in expression of the above cytokines before and after treatment and the correlation with psoriasis disease severityï¼»Psoriasis Area Severity Index(PASI) scoreï¼½, age, and disease duration were analyzed. RESULTS: The mean PASI score of the enrolled patients with moderate to severe psoriasis was 21.6 ± 11.0 before treatment and decreased to below 1 after treatment. Serum IL-6; IL-18, GROα, IFN-γ, TNF-α, VEGF-A, and IL-17A were significantly higher than normal. And IL-17A and IFN-γ were positively correlated with disease duration and age, and IL-18 was positively correlated with PASI score. The expression levels of IL-6, GROα, VEGF-A, IFN-γ, TNF-α, IL-17A and IL-23 were significantly lower after secukinumab treatment compared with those before treatment, but the expression levels of IFN-γ, VEGF-A, TARC, IL-13, and DEFB2 were still significantly higher than those of normal subjects after treatment CONCLUSIONS: secukinumab clears skin lesions by antagonizing IL-17A and simultaneously decreasing the expression levels of IL-6, GRO α, VEGF-A, IFN-γ, TNF-α, IL-17A, and IL-23.

Finite element analysis of round-window stimulation of the cochlea in patients with stapedial otosclerosis.

An active actuator coupled to the round window (RW) can transmit mechanical vibrations into the cochlea and has become a therapeutic option of hearing rehabilitation for patients with stapedial otosclerosis. A finite-element model of the human ear that includes sound transmission effects of the vestibular and cochlear aqueducts of the inner ear is adopted in this study for investigating the cochlear response to RW stimulation under stapes fixation. There are two effects due to otosclerosis of the stapes: the fixation of the stapedial annular ligament (SAL) and the increase of the stapes mass. The frequency responses of the middle ear and cochlea with normal and otosclerotic stapes are calculated under sound and RW stimulations. The results show that changes in the material property of the stapes have different effects on the cochlear responses under sound and RW stimulations. Because of the vestibuli aqueduct, the reduction in the low-frequency magnitude of the pressure difference across the cochlear partition due to SAL fixation is much smaller under RW stimulation than under sound stimulation. The results of this study help understand sound transmission during RW stimulation in patients with stapedial otosclerosis.

Transient response of the human ear to impulsive stimuli: A finite element analysis.

Nowadays, the steady-state responses of human ear to pure tone stimuli have been widely studied. However, the temporal responses to transient stimuli have not been investigated systematically to date. In this study, a comprehensive finite element (FE) model of the human ear is used to investigate the transient characteristics of the human ear in response to impulsive stimuli. There are two types of idealized impulses applied in the FE analysis: the square wave impulse (a single positive pressure waveform) and the A-duration wave impulse (both of positive and negative pressure waveforms). The time-domain responses such as the displacements of the tympanic membrane (TM), the stapes footplate (SF), the basilar membrane (BM), the TM stress distribution, and the cochlea input pressure are derived. The results demonstrate that the TM motion has the characteristic of spatial differences, and the umbo displacement is smaller than other locations. The cochlea input pressure response is synchronized with the SF acceleration response while the SF displacement response appears with some time delay. The BM displacement envelope is relatively higher in the middle cochlea and every portion of BM vibrates at its best frequency approximately. The present results provide a good understanding of the transient response of the human ear.

Numerical evaluation of implantable hearing devices using a finite element model of human ear considering viscoelastic properties.

Finite element method was employed in this study to analyze the change in performance of implantable hearing devices due to the consideration of soft tissues' viscoelasticity. An integrated finite element model of human ear including the external ear, middle ear and inner ear was first developed via reverse engineering and analyzed by acoustic-structure-fluid coupling. Viscoelastic properties of soft tissues in the middle ear were taken into consideration in this model. The model-derived dynamic responses including middle ear and cochlea functions showed a better agreement with experimental data at high frequencies above 3000 Hz than the Rayleigh-type damping. On this basis, a coupled finite element model consisting of the human ear and a piezoelectric actuator attached to the long process of incus was further constructed. Based on the electromechanical coupling analysis, equivalent sound pressure and power consumption of the actuator corresponding to viscoelasticity and Rayleigh damping were calculated using this model. The analytical results showed that the implant performance of the actuator evaluated using a finite element model considering viscoelastic properties gives a lower output above about 3 kHz than does Rayleigh damping model. Finite element model considering viscoelastic properties was more accurate to numerically evaluate implantable hearing devices.

An incus-body driving type piezoelectric middle ear implant design and evaluation in 3D computational model and temporal bone.

A new incus-body driving type transducer relying on piezoelectric stack, with broad frequency bandwidth, is proposed for use in a middle ear implant. To aid the design process of this transducer, a coupling biomechanical model of the human middle ear and the piezoelectric transducer was established by reverse engineering technology. The validity of this model was confirmed by comparing model predicted motions with experimental measurements. Based on this verified biomechanical model, the main parameters of the transducer were determined. And its power consumption was calculated. Finally, to verify the capability of the designed piezoelectric transducer, a human temporal bone experimental platform was built. And the dynamic characteristics and the stimulated performance of the piezoelectric transducer were tested. The result showed that stapes displacement stimulated by the transducer excitation at 10.5 V RMS was equivalent to that from acoustic stimulation at 100 dB SPL, which is an adequate stimulation to the ossicular chain. The corresponding power consumption is 0.31 mW per volt of excitation at 1 kHz, which is low enough for the transducer to be used in a middle ear implant. Besides, this transducer demonstrates high performance at high frequencies.