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Biomedical subjects

Hui Meng

Publications and source records attributed to Hui Meng.

17 recordsLinked to original sources

Assessment of systemic AAV-microdystrophin gene therapy in the GRMD model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by the absence of dystrophin, a membrane-stabilizing protein encoded by the DMD gene. Although mouse models of DMD provide insight into the potential of a corrective therapy, data from genetically homologous large animals, such as the dystrophin-deficient golden retriever muscular dystrophy (GRMD) model, may more readily translate to humans. To evaluate the clinical translatability of an adeno-associated virus serotype 9 vector (AAV9)-microdystrophin (μDys5) construct, we performed a blinded, placebo-controlled study in which 12 GRMD dogs were divided among four dose groups [control, 1 × 1013 vector genomes per kilogram (vg/kg), 1 × 1014 vg/kg, and 2 × 1014 vg/kg; n = 3 each], treated intravenously at 3 months of age with a canine codon-optimized microdystrophin construct, rAAV9-CK8e-c-μDys5, and followed for 90 days after dosing. All dogs received prednisone (1 milligram/kilogram) for a total of 5 weeks from day -7 through day 28. We observed dose-dependent increases in tissue vector genome copy numbers; μDys5 protein in multiple appendicular muscles, the diaphragm, and heart; limb and respiratory muscle functional improvement; and reduction of histopathologic lesions. As expected, given that a truncated dystrophin protein was generated, phenotypic test results and histopathologic lesions did not fully normalize. All administrations were well tolerated, and adverse events were not seen. These data suggest that systemically administered AAV-microdystrophin may be dosed safely and could provide therapeutic benefit for patients with DMD.

Animals↗

Pursuit--vestibular interactions in brain stem neurons during rotation and translation.

Under natural conditions, the vestibular and pursuit systems work synergistically to stabilize the visual scene during movement. How translational vestibular signals [translational vestibuloocular reflex (TVOR)] are processed in the premotor pathways for slow eye movements continues to remain a challenging question. To further our understanding of how premotor neurons contribute to this processing, we recorded neural activities from the prepositus and rostral medial vestibular nuclei in macaque monkeys. Vestibular neurons were tested during 0.5-Hz rotation and lateral translation (both with gaze stable and during VOR cancellation tasks), as well as during smooth pursuit eye movements. Data were collected at two different viewing distances, 80 and 20 cm. Based on their responses to rotation and pursuit, eye-movement-sensitive neurons were classified into position-vestibular-pause (PVP) neurons, eye-head (EH) neurons, and burst-tonic (BT) cells. We found that approximately half of the type II PVP and EH neurons with ipsilateral eye movement preference were modulated during TVOR cancellation. In contrast, few of the EH and none of the type I PVP cells with contralateral eye movement preference modulated during translation in the absence of eye movements; nor did any of the BT neurons change their firing rates during TVOR cancellation. Of the type II PVP and EH neurons that modulated during TVOR cancellation, cell firing rates increased for either ipsilateral or contralateral displacement, a property that could not be predicted on the basis of their rotational or pursuit responses. In contrast, under stable gaze conditions, all neuron types, including EH cells, were modulated during translation according to their ipsilateral/contralateral preference for pursuit eye movements. Differences in translational response sensitivities for far versus near targets were seen only in type II PVP and EH cells. There was no effect of viewing distance on response phase for any cell type. When expressed relative to motor output, neural sensitivities during translation (although not during rotation) and pursuit were equivalent, particularly for the 20-cm viewing distance. These results suggest that neural activities during the TVOR were more motorlike compared with cell responses during the rotational vestibuloocular reflex (RVOR). We also found that neural responses under stable gaze conditions could not always be predicted by a linear vectorial addition of the cell activities during pursuit and VOR cancellation. The departure from linearity was more pronounced for the TVOR under near-viewing conditions. These results extend previous observations for the neural processing of otolith signals within the premotor circuitry that generates the RVOR and smooth pursuit eye movements.

Action Potentials↗

Multiple reference frames for motion in the primate cerebellum.

Knowledge of body motion through space is necessary for spatial orientation, self-motion perception, and postural control. Yet, sensory afferent signals may not directly provide such information to the brain. Because motion detected by the vestibular end organs is encoded in a head-fixed frame of reference, a coordinate transformation is thus required to encode body motion. In this study, we investigated whether cerebellar motion-sensitive neurons encode the translation of the body through space. We systematically changed both the direction of motion relative to the body and the static orientation of the head relative to the trunk. The activities of motion-sensitive neurons in the most medial of the deep cerebellar nuclei, the rostral fastigial nucleus, were compared with those in the brainstem vestibular nuclei. We found a distributed representation of reference frames for motion in the rostral fastigial nucleus, in contrast to cells in the vestibular nuclei, which primarily encoded motion in a head-fixed reference frame. This differential representation of motion-related information implies potential differences in the functional roles of these areas.

Acceleration↗

Eye movements evoked by selective saccular nerve stimulation in cats.

OBJECTIVE: Because of technical obstacles in controlling current spread to adjacent peripheral nerve, eye movements evoked by activation of the otolith organs have not been investigated in detail compared to eye movements evoked by activation of the canal organs. We attempted to solve this problem by applying more sensitive methods using fine needle and strictly controlling stimulus current intensity compare with filed potential for selective stimulation. METHODS: Eye movements evoked by selective, unilateral saccular (SAC) nerve stimulation were investigated using both electrooculography (EOG) and video recording in decerebrated cats in the presence or absence of anesthesia. Electrical stimulation was applied to the SAC nerve through implanted acupuncture needles. RESULTS: In the absence of anesthesia and with stimulus intensities less than (3.1 +/- 2.7) x N(1)T, we found supraduction in both eyes or in either the ipsilateral or contralateral eye of different cats. We observed downward eye movements using a stronger stimulus intensity ((6.2 +/- 2.9)) x N(1)T). The threshold for downward eye movements was significantly greater than that for upward eye movements (P < 0.05). In anesthetized cats, only downward eye movements were observed when stimulus intensities less than 10 x N(1)T ((7.8 +/- 2.3) x N(1)T) were used. CONCLUSION: These results confirm the known sacculo-ocular anatomical connections, which are involved predominantly in vertical eye movements. Because the sacculo-ocular connections are relatively weak, the normal supraduction evoked by SAC activation can be easily modified by factors such as level of anesthesia and the method of stimulation.

Animals↗

Measurement of flow modification in phantom aneurysm model: comparison of coils and a longitudinally and axially asymmetric stent--initial findings.

Dye-dilution imaging sequences were performed and time-density curves were constructed in elastomer vessel aneurysm models to demonstrate the effectiveness of coils and an asymmetric stent in disrupting standard vortex flow. Compared with the use of coils, the use of stents led to marked flow modification, as seen with imaging sequences, and substantially slower inflow, as indicated by time-density curves, owing to the low-porosity region of the stent that covers the aneurysm orifice. These flow examination results indicate that potentially favorable flow modification features can be created by using the described asymmetric stent design, the use of which may lead to alternative methods of image-guided endovascular cerebral aneurysm therapy.

Blood Vessel Prosthesis Implantation↗

Intrinsic speckle noise in off-axis particle holography.

In holographic imaging of particle fields, the interference among coherent wave fronts associated with particle scattering gives rise to intrinsic speckle noise, which sets a fundamental limit on the amount of information that particle holography can deliver. It has been established that the intrinsic speckle noise is especially severe in in-line holography because of superposition of virtual image waves, the direct transmitted wave, and the real image. However, at sufficiently high particle number densities, such as those typical in holographic particle image velocimetry (HPIV) applications, intrinsic speckle noise also arises in off-axis particle holography from self-interference among wave fronts that form the real image of particles. To overcome the latter problem we have constructed a mathematical model that relates the first- and second-order statistical properties of the intrinsic speckle noise to relevant holographic system parameters. Consistent with our experimental data, the model provides a direct estimate of the information capacity of particle holography. We show that the noise-limited information capacity can be expressed as the product of particle number density and the extent of the particle field along the optical axis. A large angular aperture of the hologram contributes directly to achievement of high information capacity. We also show that filtering in either digital or optical form is generally ineffective in removing the intrinsic speckle noise from the particle image as a result of the similar spectral properties of the two. These findings emphasize the importance of angular aperture in designing holographic particle imaging systems.

Journal Article↗

Effects of arterial geometry on aneurysm growth: three-dimensional computational fluid dynamics study.

OBJECT: Few researchers have quantified the role of arterial geometry in the pathogenesis of saccular cerebral aneurysms. The authors investigated the effects of parent artery geometry on aneurysm hemodynamics and assessed the implications relative to aneurysm growth and treatment effectiveness. METHODS: The hemodynamics of three-dimensional saccular aneurysms arising from the lateral wall of arteries with varying arterial curves (starting with a straight vessel model) and neck sizes were studied using a computational fluid dynamics analysis. The effects of these geometric parameters on hemodynamic parameters, including flow velocity, aneurysm wall shear stress (WSS), and area of elevated WSS during the cardiac cycle (time-dependent impact zone), were quantified. Unlike simulations involving aneurysms located on straight arteries, blood flow inertia (centrifugal effects) rather than viscous diffusion was the predominant force driving blood into aneurysm sacs on curved arteries. As the degree of arterial curvature increased, flow impingement on the distal side of the neck intensified, leading to elevations in the WSS and enlargement of the impact zone at the distal side of the aneurysm neck. CONCLUSIONS: Based on these simulations the authors postulate that lateral saccular aneurysms located on more curved arteries are subjected to higher hemodynamic stresses. Saccular aneurysms with wider necks have larger impact zones. The large impact zone at the distal side of the aneurysm neck correlates well with other findings, implicating this zone as the most likely site of aneurysm growth or regrowth of treated lesions. To protect against high hemodynamic stresses, protection of the distal side of the aneurysm neck from flow impingement is critical.

Anthropometry↗

[Early-stage hemodynamic changes in dogs with gunshot wound in seawater].

OBJECTIVE: To investigate the hemodynamic changes in the early stages of gunshot wound of dogs in seawater for exploring early treatment protocol. METHOD: Fourteen conventional Beagles models undergoing gunshot wound in seawater were used along with another 2 dogs receiving the wound on land to serve as control. After the dogs were rescued from the seawater, the respiration (R), heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), central venous pressure (CVP), pulmonary arterial wedge pressure (PAWP), and cardiac output (CO) were measured continuously in the early stages of the wound (53.62+/-12.19 min following injury), followed by statistical analysis of the results. RESULTS: Compared with the control group, the hemodynamic disturbance of the dogs receiving the wound in seawater was relatively severe during the first 15 min of the wound. The mortality tended to descend relevant to the position of the wounds, in the order of the head, chest, abdomen and limbs. CONCLUSIONS: Gunshot wound in seawater may cause severe hemodynamic changes, resulting in progressive dysfunction of circulation and high mortality rate. Early treatment should be targeted at hemodynamic stabilization in accordance to the characteristic changes during the early stages of the wound.

Animals↗

Digital holography of particle fields: reconstruction by use of complex amplitude.

Digital holography appears to be a strong contender as the next-generation technology for holographic diagnostics of particle fields and holographic particle image velocimetry for flow field measurement. With the digital holographic approach, holograms are directly recorded by a digital camera and reconstructed numerically. This not only eliminates wet chemical processing and mechanical scanning, but also enables the use of complex amplitude information inaccessible by optical reconstruction, thereby allowing flexible reconstruction algorithms to achieve optimization of specific information. However, owing to the inherently low pixel resolution of solid-state imaging sensors, digital holography gives poor depth resolution for images, a problem that severely impairs the usefulness of digital holography especially in densely populated particle fields. This paper describes a technique that significantly improves particle axial-location accuracy by exploring the reconstructed complex amplitude information, compared with other numerical reconstruction schemes that merely mimic traditional optical reconstruction. This novel method allows accurate extraction of particle locations from forward-scattering particle holograms even at high particle loadings.

Journal Article↗

Eye movements evoked by the selective stimulation of the utricular nerve in cats.

OBJECTIVE: Eye movements evoked by otolith organ are not well-investigated compare with canal related eye movements due to the technical difficulties. We try to solve this problem by means of our methods. METHODS: Eye movements evoked by selective utricular (UT) nerve stimulation were investigated using both electrooculography (EOG) and video recording in decerebrated cats in the presence or absence of anesthesia. Electrical stimulation was applied to the UT nerve through implanted acupuncture needles. RESULTS: In the absence of anesthesia and with stimulus intensities less than 2.6+/-0.7 x N(1)T, we found ipsilaterally directed horizontal eye movements in both eyes in one cat, abduction in the ipsilateral eye in two cats, and adduction in the contralateral eye in another cat. Other types of eye movements (e.g., supraduction or diagonal eye movements) were observed in both eyes of cats in the absence of anesthesia at a stimulus intensity of 12.2+/-7.6 x N(1)T, an intensity in which current spread to the adjacent nerve could not be ruled out. In the presence of anesthesia, UT nerve stimulation alone failed to evoke horizontal eye movements, but with an intensity 13.8+/-6.4 x N(1)T, supraduction or diagonal eye movements were evoked. UT nerve stimulation at 2-3 x N(1)T facilitated horizontal eye movements induced by ipsilateral abducens (AB) nucleus stimulation or contralateral horizontal canal nerve stimulation. CONCLUSION: This is the first report to our knowledge in which UT nerve-evoked horizontal eye movements are documented. These results confirm the known monosynaptic and disynaptic anatomical connections from utricular primary afferents to the ipsilateral AB nucleus neurons.

Abducens Nerve↗

Intrinsic aberrations due to Mie scattering in particle holography.

Holography of small particles is a newly revived topic because of its importance in holographic particle image velocimetry (HPIV). However, the property of particle images formed through holography remains largely unexplored. This fact undermines the measurement reliability of HPIV techniques and has become one of the obstacles in the full deployment of HPIV. We study the intrinsic aberrations in the holographic particle image introduced by particle light scattering and investigate how accurately holography can deliver information about the particles that are being imaged. Consistent with our experimental observations, simulations based on Mie scattering theory show that even with a perfect hologram the reconstructed particle images demonstrate complex three-dimensional morphologies and bodily shifts. These characteristics, manifested as image aberrations, result from uneven scattering amplitude and phase distributions across the finite aperture of the hologram. Such aberrations degrade the signal-to-noise ratio in the reconstructed image as well as introducing systematic errors in detected particle image positions. We examine the effect of these aberrations on HPIV measurements.

Journal Article↗

A new three-layer-funnel-shaped esophagogastric anastomosis for surgical treatment of esophageal carcinoma.

AIM: To reduce the incidence of postoperative anastomotic leak, stenosis, gastroesophageal reflux (GER) for patients with esophageal carcinoma, and to evaluate the conventional method of esophagectomy and esophagogastroplasty modified by a new three-layer-funnel-shaped (TLF) esophagogastric anastomotic suturing technique. METHODS: From January 1997 to October 1999, patients with clinical stage I and II (IIa and IIb) esophageal carcinoma, which met the enrollment criteria, were surgically treated by the new method (Group A) and by conventional operation (Group B). All the patients were followed at least for 6 months. Postoperative outcomes and complications were recorded and compared with the conventional method in the same hospitals and with that reported previously by McLarty et al in 1997 (Group C). RESULTS: 58 cases with stage I and II (IIa and IIb) esophageal carcinoma, including 38 males and 20 females aged from 34 to 78 (mean age: 57), were surgically treated by the TLF anastomosis and 64 by conventional method in our hospitals from January 1997 to October 1999. The quality of swallowing was improved significantly (Wilcoxon W=2 142, P=0.0 001) 2 to 3 months after the new operation in Group A. Only one patient had a blind anastomatic fistula diagnosed by barium swallow test 2 months but healed up 3 weeks later. Postoperative complications occurred in 25 (43 %) patients, anastomotic stenosis in 8 (14 %), and GER in 13 (22 %). The incidences of postoperative anastomotic leak, stenosis and GER were significantly decreased by the TLF anastomosis method compared with that of conventional methods (chi(2)=6.566, P=0.038; chi(2)=10.214, P=0.006; chi(2)=21.265, P=0.000). CONCLUSION: The new three-layer-funnel-shaped esophagogastric anastomosis (TLFEGA) has more advantages to reduce postoperative complications of anastomotic leak, stricture and GER.

Adult↗

[Quantitative study of bacteriological infections in dogs undergoing gunshot wound in seawater].

OBJECTIVE: To investigate the changes in bacterial proliferation and the time of infection occurrence in dogs wounded by gunshot in seawater. METHOD: Fourteen canine models of gunshot wound in seawater were established, with another 2 dogs receiving the wound without seawater immersion serving as control. Gross observation and quantitative bacterial analysis were performed at 0, 6, 12 and 24 h after the injury respectively, and two dynamic models for the bacterial growth were set up on the basis of statistical analysis of the results. RESULTS: Bacterial quantity in both of the two groups tended to increase with time, but at each time point after the injury, the seawater group had higher bacterial count than the other group. Within 6 h after the injury, the bacterial count reached the critical point for clinical infection in seawater group. The two bacterial growth dynamics models were (1) Y=9.12 x 10(3+0.247X) and (2) Y=1.35 x 10(3+0.227X) for the seawater group and land group respectively, with the variant X representing time after gunshot injury, and Y the bacterial count per gram tissue. Using the dynamic models, we found that to reach the same bacteria count, the land group needed 4 h more than the seawater group(4.2 h). CONCLUSIONS: Bacterial proliferation is accelerated in the wounds in seawater to result in earlier infection onset with more severity, suggesting that early debridement within 4 h after the injury, complete washing of the wound and early administration of the antibiotics are necessary for the wound management.

Animals↗

[Lung transplantation for treatment of pulmonary cystic fibrosis: report of one case].

A right single lung transplantation was performed in a 17-year-old female patient with end-stage cystoid pulmonary fibrosis and without cardiopulmonary bypass in June 2003. The donor lung was perfused with cold UW solution with a cold ischemic time of 280 min. The patient weaned from ventilator on the next day of operation (18 h later) and was able to walk at the fourth day postoperatively. Immunosuppression included methylprednisolone used before FK 506, mycophenolate mofetil and prednisone dosed after operation. The patient remains well a month after operation with significant improvement of the lung function and enjoys normal life.

Adolescent↗

Morphology of physiologically identified otolith-related vestibular neurons in cats.

The morphology of physiologically identified otolith nerve-activated vestibular neurons was investigated using intracellular injections of horseradish peroxidase (HRP). Eleven utricular, 11 saccular and three utricular/saccular nerve-activated vestibular neurons were labeled with HRP. All of these neurons except one were secondary neurons, the exception being a convergent neuron. The labeled neurons were pyramidal, elongated and ovoidal in shape. Most of the labeled cells were medium to large (mean diameter: > or =30 micro m). There was no apparent correlation between morphology and the different types of otolith nerve-activated vestibular neurons. Thus, it seems likely that the functional type of vestibular neurons cannot be presumed on the basis of their morphology alone.

Animals↗

Morphological changes in canine lungs perfused with modified Euro-Collins solution.

OBJECTIVE: To investigate the structural changes in canine lungs perfused with modified Euro-Collins solution (mECS), thus providing insight into the preservation of the donor lung tissue for transplantation. METHODS: Six dogs were anesthetized and pulmonary perfusion with mECS (4 degrees Celsius) was performed before the lungs were isolated thereafter and stored at 4 to 8 degrees Celsius for 30, 60, 120, 180, 240 min respectively, after which tissue samples of the donor lung were taken for morphological observation with both light and transmission electron microscope. RESULTS: Immediately after reperfusion, the pulmonary tissues exhibited clear and intact structures,showing that mitochondrion swelled slightly in the alveolar epithelial cells (AECs). Mild edema occurred in the alveolar wall and the tissues around the veins at 30 min after preservation, which exacerbated to dilapidation of the alveolar wall and obvious tumefaction of the mitochondrion in the AECs at 60 min. At 180 min, rupture of alveolar wall and emergence of the alveolus was observed at 120 min, and a few pulmonary bullae were formed, the AECs (I) of which presented vacuolar changes in the cytoplasma and mitochondrion, with disappearance of the tiny villus of the AECs (II) at 240 min. CONCLUSION: Within 4 h of preservation in mECS, the pulmonary tissues do not undergo obvious changes as signs of injury, which, however, may not be the case after longer preservation.

Animals↗

[Effect of jinshui-liujun decoction on chronic bronchitis in rats].

OBJECTIVE: To study of the quality standard about Jinshui Liujun decoction. METHODS: The chronic broncitis model of rat was induced by injecting LPS into rat's trachea. Then, the number of WBC, SV, PS were detected. RESULTS: Both Jinshui Liujun decoction and hesperidin can improve the content of PS and reduce the number of WBC. There were statistical difference between the therapeutic groups and the model group, and the changes of bronchi between the therapeutic group were similar. But the SV of hesperidin group was bigger than Jinshui Liujun decoction group, and the PS of hesperidin group was less than Jinshui Liujun decoction group. CONCLUSION: It was feasible that the content of hesperidin in Jinshui Liujun decoction was as primary quality control index.

Angelica sinensis↗