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Biomedical subjects

Ning Hu

Publications and source records attributed to Ning Hu.

14 recordsLinked to original sources

CASZ1 regulates the maturation of outer hair cells and is required for hearing in mice.

The transcription factor ATOH1 is a master regulator of mechanosensory hair-cell (HC) development in the ear. Here, we report that its target gene Casz1 regulates the maturation of outer HCs (OHCs). Genetic deletion of Casz1 during (but not after) cochlear development in the mouse caused: hearing loss; disorganization of mechanosensory stereocilia bundles in OHCs; reduced F-actin density in OHC cuticular plates; progressive OHC loss; and mild morphological alterations in inner HCs. This deletion also altered gene expression, delaying downregulation of genes expressed in immature OHCs, including the actin regulator-encoding gene Coro2a, and accelerating upregulation of genes expressed in mature OHCs. Deleting Coro2a in Casz1 mutant mice restored F-actin density in cuticular plates but increased stereocilia bundle disorganization and hearing thresholds, revealing that CORO2A provides an overall beneficial effect. Our data indicate that CASZ1 regulates transcriptional and morphological maturation of OHCs, and that CASZ1 in maturing HCs is necessary for hearing.

CASZ1↗

Cell-type-specific genetic associations in Lewy body dementia identified using single-cell eQTL-based Mendelian randomization.

BACKGROUND: Lewy body dementia (LBD) is a complex neurodegenerative disorder marked by α-synuclein aggregation and dual impairment of cognitive and motor function.While genome-wide association studies have identified risk loci, the cellular mechanisms linking genetic variation to disease susceptibility remain largely unexplored. METHODS: We performed single-cell transcriptome-wide Mendelian randomization using brain cell-type-specific eQTLs across eight major cell types. Genetic associations were evaluated using inverse-variance weighted models, followed by Bayesian colocalization analysis. Replication was performed in independent stratified LBD cohorts based on APOE ε4 carrier status. Phenome-wide association analysis was included as a supplementary, descriptive assessment of cross-trait associations. RESULTS: Expression of ANKRD65 in excitatory neurons was significantly associated with reduced LBD risk (odds ratio = 0.65, 95 % CI: 0.52-0.81, p = 0.00013). This association passed a false discovery rate of 0.1 and showed strong evidence of colocalization (posterior probability = 0.93). Effect direction was consistent across APOE ε4+ and ε4- LBD subgroups in independent cohorts. No genome-wide significant associations were observed with non-neurological traits in the phenome-wide analysis. CONCLUSIONS: Our findings identify a genetically supported, cell-type-resolved association between ANKRD65 expression in excitatory neurons and LBD risk. This study demonstrates the value of integrating cell-resolved transcriptomic regulation with genetic inference to pinpoint functionally relevant targets in neurodegenerative diseases.

Humans↗

Application of multislice spiral CT for guidance of insertion of thoracic spine pedicle screws: an in vitro study.

To investigate the value of the guidance of three dimensional (3-D) reconstruction of multi-slice spiral CT (MSCT) for the placement of pedicle screws, the 3-D anatomical data of the thoracic pedicles were measured by MSCT in two embalmed human cadaveric thoracic pedicles spines (T1-T10) to guide the insertion of pedicle screws. After pulling the screws out, the pathways were filled with contrast media. The PW, PH, TSA and SSA of developed pathways were measured on the CT images and they were also measured on the real objects by caliper and goniometer. Analysis of variance demonstrated that the difference between the CT scans and real objects had no statistical significance (P > 0.05). Moreover, the difference between pedicle axis and developed pathway also had no statistical significance (P > 0.05). The data obtained from 3-D reconstruction of MSCT demonstrated that individualized standards, are not only accurate but also helpful for the successful placement of pedicle screws.

Bone Screws↗

[Fabrication and application in vitro of pedicle guide device for pedicle screws insertion].

OBJECTIVE: To evaluate the accuracy of pedicle guide device for the placement of the pedicle screws. METHODS: Pedicle guide device was designed and made for the anatomical trait of pedicle. The 3-D anatomical data of the thoracic pedicles were measured by multi-slice spiral CT in two embalmed human cadaveric thoracic pedicles spine (T1-T10). Depending on transverse section angle (TSA) and sagittal section angle (SSA) of pedicle axis, the degree of horizontal dial and sagittal dial were adjusted in the guide device. The screws were inserted bilaterally in the thoracic pedicles by using the device. After pulling the screws out, the pathways were filled with contrast media. The TSA and SSA of developed pathways were measured. RESULTS: Analysis of the difference between pedicle axis and developed pathway was of no statistical significance (P > 0.05). CONCLUSION: The guide device could be easily operated and guarantee high accuracy of the pathways of screws and the incidence of pedicle penetration could be significantly reduced.

Adult↗

Spatial distribution of electrically induced high frequency vibration on basilar membrane.

We reported that the electrically evoked basilar membrane (BM) vibration at frequencies above the best frequency (BF) showed a lowest BM velocity magnitude, called a "dip", in the velocity-frequency spectra, indicating a cancellation. In the present study, we measured the high frequency BM motion as functions of the longitudinal and radial locations. Measurements were taken at three longitudinal locations in the first turn and the hook region: 14.9, 15.8 and 16.8 mm from the apex, corresponding to the BFs of 17, 21.3 and 28.0 kHz calculated from Greenwood [J. Acoust. Soc. Am. 87, 2592], and at different radial locations across the width of the BM. It was found that the dip frequency (DF) varied with the longitudinal and radial locations. In the longitudinal direction, the average value of the DF was 49.6, 55.6 and 72.8 kHz, respectively. Thus, the longitudinal distribution of the high frequency BM vibration was correlated with the BF. In the radial direction, there was consistent variation of the response spectrum such that the dip was mainly evident in the pectinate zone of the BM. These results imply that the high frequency BM motion is related to mechanical properties of the cochlear partition, including the outer hair cells (OHCs) themselves. Data also indicate different vibration modes across the width of the organ of Corti.

Acoustic Stimulation↗

The Allen-Fahey experiment extended.

An ingenious experiment has been performed by Allen and Fahey [J. Acoust. Soc. Am. 92, 178-188 (1992)], in which they attempted to estimate the gain of the cochlear amplifier by comparing responses to the 2 f1-f2 distortion product (DP) in the outer ear canal (otoacoustic emissions) and from an auditory-nerve fiber. Results were essentially negative: no evidence of cochlear amplification was found in that experiment. A variation of that experiment is reported here, where DP responses in the outer ear canal are compared with mechanical responses of the basilar membrane. This variation does not suffer from the major limitation in the original experiment in the choice of possible frequency ratios. Results confirm and extend those of Allen and Fahey entirely. Apparently, the gain of the cochlear amplifier cannot be measured in this way. It is argued that the retrograde wave going to the stapes is most likely reduced in magnitude by wave interference when the two primary frequencies approach each other. Such a reduction does not take place in the forward-going wave to the location tuned to the DP frequency. This explanation is illustrated on the basis of results of earlier experiments on the movements of the basilar membrane.

Animals↗

[Correlation of intersubspecific hybrid rice spikelet fertilization rate with temperature and related statistic model].

Using four types of rice, i. e., indica-japonica hybrid, intermediate hybrid, indica and japonica cultivars as test materials, this paper studied the sensitivity of intersubspecific hybrid rice to climatic factors, and the correlations between spikelet fertilization rate (SFR) and daily meteorological factors during 2000 and 2001. The results showed that the SFR of intersubspecific hybrids was lower than that of indica and japonica cultivars. Among eleven meteorological factors, temperature was the key factor, and the mean temperature within five or seven days around panicle flower blooming affected the SFR significantly. A comprehensive model of SFR-temperature was established, with which, the fittest temperature and safe temperature for fertilization of intersubspecific hybrids was estimated to be 28.2 - 29.3 degrees C and 23.4 - 24.3 degrees C, 2.2 degrees C and 1.5 degrees C higher than those of indica and japonica cultivars, respectively. It was suggested that the safe heading date for planting intersubspecific hybrid should be moved up to the last ten-day of September to the first ten-day of October in southern China, the first ten-day of September in middle and lower reaches of Yangtze River Valley, and the last ten-day of August to the first ten-day of September in rice planting area between Yangtze and Huai River.

Chromosomes, Plant↗

Organ of Corti potentials and the motion of the basilar membrane.

During sound stimulation, receptor potentials are generated within the sensory hair cells of the cochlea. Prevailing theory states that outer hair cells use the potential-sensitive motor protein prestin to convert receptor potentials into fast alterations of cellular length or stiffness that boost hearing sensitivity almost 1000-fold. However, receptor potentials are attenuated by the filter formed by the capacitance and resistance of the membrane of the cell. This attenuation would limit cellular motility at high stimulus frequencies, rendering the above scheme ineffective. Therefore, Dallos and Evans (1995a) proposed that extracellular potential changes within the organ of Corti could drive cellular motor proteins. These extracellular potentials are not filtered by the membrane. To test this theory, both electric potentials inside the organ of Corti and basilar membrane vibration were measured in response to acoustic stimulation. Vibrations were measured at sites very close to those interrogated by the recording electrode using laser interferometry. Close comparison of the measured electrical and mechanical tuning curves and time waveforms and their phase relationships revealed that those extracellular potentials indeed could drive outer hair cell motors. However, to achieve the sharp frequency tuning that characterizes the basilar membrane, additional mechanical processing must occur inside the organ of Corti.

Acoustic Stimulation↗

Biocompatibility studies on fibrin glue cultured with bone marrow mesenchymal stem cells in vitro.

By culturing bone marrow mesenchymal stem cells of rabbits with fibrin glue in vitro, the biocompatibility of fibrin glue was investigated to study whether this material can be used as scaffolds in bone tissue engineering. After 2-months old New Zealand rabbits had been anesthetized, about 4-6 ml of bone marrow were aspirated from rabbit femoral trochanter. The monocytes suspension was aspirated after bone marrow was centrifuged with lymphocyte separating medium and cultured primarily. Then the cells were divided into two groups: one was cultured with complete medium and the other with induced medium. The cells of the two groups were collected and inoculated to the culture plate containing fibrin glue. In the control group, cells were inoculated without fibrin glue. The implanted cells and materials were observed at different stages under a phase-contrast microscope and scanning electron microscope. MTT and alkaline phosphatase (ALP) were measured. Bone marrow mesenchymal stem cells grew on the surface of fibrin glue and adhered to it gradually. Cells light absorption value (A value) and the ALP content showed no significant difference. Fibrin glue had no inhibitory effect on cell morphology, growth, proliferation and differentiation. It has good biocompatibility and can be used as scaffold materials for bone marrow mesenchymal stem cells in bone tissue engineering.

Animals↗

Electrode configuration influences action potential initiation site and ensemble stochastic response properties.

The configuration of intracochlear electrodes used to electrically stimulate the auditory nerve influences the ensemble fiber response. For example, monopolar stimulation produces lower thresholds and greater spread of excitation than does bipolar stimulation. We used two approaches to investigate how the ensemble of auditory-nerve fibers responds to stimulation delivered by different electrode configurations. As the electrically evoked compound action potential (ECAP) reflects the ensemble response of the nerve, we used its morphology and changes with stimulus level to assess issues related to site-of-excitation and fiber recruitment. In our first approach, feline ECAPs were obtained using a nucleus-style banded electrode array. ECAP latency functions indicated that bipolar stimulation can initiate action potentials at more peripheral sites than does monopolar stimulation. We observed double-peaked ECAPs with bipolar and tripolar stimulation, suggesting excitation of both peripheral and central neural processes. Finally, we observed in some cases a tendency for monopolar stimulation to produce wider ECAP potentials, consistent with the notion that monopolar stimulation excites a broader spatial extent of the fiber population. In our second approach, we applied a simple model to published surveys of single-fiber responses to provide insight into the stochastic properties of the ensemble response. Our results suggest that broader recruitment of fiber activity produced by monopolar stimulation results in a population response with more probabilistic response characteristics and ensemble spike jitter. These observations and our ECAP results are consistent with reports of perceptual advantages attributed to monopolar or other less-focused modes of stimulation.

Animals↗

Auditory response to intracochlear electric stimuli following furosemide treatment.

The influence of functional hair cells on electrical stimulation of the auditory nerve is an important issue as individuals with significant residual hearing are now cochlear implant candidates. Previous work has shown that chemical deafening during the course of acute experiments changes the auditory nerve's responses to electrical stimulation [Third Quarterly Progress Report, NIH contract N01-DC-9-2106 (2000), Final Report, NIH Contract N01-DC-9-2106 (2002)]. This study extended that work by investigating the changes and subsequent recovery following furosemide injections which reversibly impair hair-cell function [Hear. Res. (1980) 79-89; Hear. Res. 14 (1984) 305-314, J. Physiol. 347 (1984) 685-696; Hear. Res. 71 (1993) 202-207]. Acoustic sensitivity of guinea pig subjects was repeatedly monitored with the click-evoked compound action potential. Responses to single biphasic electric pulses and biphasic electric pulse trains delivered by a monopolar intracochlear electrode were also repeatedly assessed using the electrically evoked compound action potential (ECAP). Our measures demonstrated a clear relationship between the state of hair-cell function and ECAP responses, as changes in the latter coincided with the loss or recovery of acoustic sensitivity. ECAP growth functions demonstrated increased slope and increased maximum (saturation) amplitude. Both trends were reversible and followed approximately the time course of post-furosemide hearing recovery. Additional changes were observed using electric pulse-train stimulation: (1) the magnitude of ECAP amplitude alternation (observed in response to successive stimulus pulses) increased, (2) the degree of ECAP adaptation (measured 80-100 ms after pulse-train onset) increased, and (3) the degree of refractoriness (measured by the ratio of ECAP amplitudes to the second and first pulses) tended to increase. All these trends are consistent with the hypothesis that functional hair cells desynchronize the population of auditory nerve fibers, thereby changing the electrically evoked responses. Viable hair cells may therefore provide positive effects on auditory response to electric stimuli delivered to implant patients with residual hearing, as they may enhance the random activity of the stimulated nerve.

Animals↗

Prostate boundary segmentation from 3D ultrasound images.

Segmenting, or outlining the prostate boundary is an important task in the management of patients with prostate cancer. In this paper, an algorithm is described for semiautomatic segmentation of the prostate from 3D ultrasound images. The algorithm uses model-based initialization and mesh refinement using an efficient deformable model. Initialization requires the user to select only six points from which the outline of the prostate is estimated using shape information. The estimated outline is then automatically deformed to better fit the prostate boundary. An editing tool allows the user to edit the boundary in problematic regions and then deform the model again to improve the final results. The algorithm requires less than 1 min on a Pentium III 400 MHz PC. The accuracy of the algorithm was assessed by comparing the algorithm results, obtained from both local and global analysis, to the manual segmentations on six prostates. The local difference was mapped on the surface of the algorithm boundary to produce a visual representation. Global error analysis showed that the average difference between manual and algorithm boundaries was -0.20 +/- 0.28 mm, the average absolute difference was 1.19 +/- 0.14 mm, the average maximum difference was 7.01 +/- 1.04 mm, and the average volume difference was 7.16% +/- 3.45%. Variability in manual and algorithm segmentation was also assessed: Visual representations of local variability were generated by mapping variability on the segmentation mesh. The mean variability in manual segmentation was 0.98 mm and in algorithm segmentation was 0.63 mm and the differences of about 51.5% of the points comprising the average algorithm boundary are insignificant (P < or = 0.01) to the manual average boundary.

Algorithms↗

Selection of surgical interference in mastoidectomy with tympanoplasty.

OBJECTIVE: To discuss the long-term results of different surgical patterns for chronic suppurative otitis media. METHODS: The data of 231 cases of chronic suppurative otitis media who underwent open-mastoidectomy with tympanoplasty (OMT), combined approach tympanoplasty (CAT), and intact bridge mastotymplasty (IBM) and were followed up for 2 - 5 years from 1990 to 2001 were collected to analyze the surgical technology, long-term recurrence rate, and level of hearing improvement. RESULTS: The improved hearing threshold level of air conduction in 0.5, 1, 2 KHz was 21 dBHL after IBM, significantly higher than that after OMT (12 dBHL) and that after CAT (9.5 dBHL). The long-term recurrence rate was 24.4% after CAT, higher than that after IBM (8.3%) and that after OMT (5.8%). CONCLUSION: IBM is a good choice for preserving or improving hearing based on eradication of the focus among patients with chronic suppurative otitis media.

Adolescent↗