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Biomedical subjects

Hong Du

Publications and source records attributed to Hong Du.

At least 19 recordsLinked to original sources

Analysis of 15 STR loci in Chinese population from Sichuan in West China.

Allele frequencies for 15 STR loci found in PowerPlex 16 System kit were determined in a sample of 200 unrelated individuals living in Sichuan area in west China. The values of observed heterozygosity (Ho), power of discrimination (PD), probability of paternity exclusion (PE) and polymorphism information content (PIC) were calculated. All loci were in accordance with Hardy-Weinberg equilibrium (p<0.05). The obtained frequency distributions were compared with other previously reported population data.

China↗

Segmented crystalline scintillators: empirical and theoretical investigation of a high quantum efficiency EPID based on an initial engineering prototype CsI(TI) detector.

Modern-day radiotherapy relies on highly sophisticated forms of image guidance in order to implement increasingly conformal treatment plans and achieve precise dose delivery. One of the most important goals of such image guidance is to delineate the clinical target volume from surrounding normal tissue during patient setup and dose delivery, thereby avoiding dependence on surrogates such as bony landmarks. In order to achieve this goal, it is necessary to integrate highly efficient imaging technology, capable of resolving soft-tissue contrast at very low doses, within the treatment setup. In this paper we report on the development of one such modality, which comprises a nonoptimized, prototype electronic portal imaging device (EPID) based on a 40 mm thick, segmented crystalline CsI(Tl) detector incorporated into an indirect-detection active matrix flat panel imager (AMFPI). The segmented detector consists of a matrix of 160 x 160 optically isolated, crystalline CsI(Tl) elements spaced at 1016 microm pitch. The detector was coupled to an indirect detection-based active matrix array having a pixel pitch of 508 microm, with each detector element registered to 2 x 2 array pixels. The performance of the prototype imager was evaluated under very low-dose radiotherapy conditions and compared to that of a conventional megavoltage AMFPI based on a Lanex Fast-B phosphor screen. Detailed quantitative measurements were performed in order to determine the x-ray sensitivity, modulation transfer function, noise power spectrum, and detective quantum efficiency (DQE). In addition, images of a contrast-detail phantom and an anthropomorphic head phantom were also acquired. The prototype imager exhibited approximately 22 times higher zero-frequency DQE (approximately 22%) compared to that of the conventional AMFPI (approximately 1%). The measured zero-frequency DQE was found to be lower than theoretical upper limits (approximately 27%) calculated from Monte Carlo simulations, which were based solely on the x-ray energy absorbed in the detector-indicating the presence of optical Swank noise. Moreover, due to the nonoptimized nature of this prototype, the spatial resolution was observed to be significantly lower than theoretical expectations. Nevertheless, due to its high quantum efficiency (approximately 55%), the prototype imager exhibited significantly higher DQE than that of the conventional AMFPI across all spatial frequencies. In addition, the frequency-dependent DQE was observed to be relatively invariant with respect to the amount of incident radiation, indicating x-ray quantum limited behavior. Images of the contrast-detail phantom and the head phantom obtained using the prototype system exhibit good visualization of relatively large, low-contrast features, and appear significantly less noisy compared to similar images from a conventional AMFPI. Finally, Monte Carlo-based theoretical calculations indicate that, with proper optimization, further, significant improvements in the DQE performance of such imagers could be achieved. It is strongly anticipated that the realization of optimized versions of such very high-DQE EPIDs would enable megavoltage projection imaging at very low doses, and tomographic imaging from a "beam's eye view" at clinically acceptable doses.

Biomedical Engineering↗

Macrophage-specific expression of human lysosomal acid lipase corrects inflammation and pathogenic phenotypes in lal-/- mice.

Lysosomal acid lipase (LAL) hydrolyzes cholesteryl esters and triglycerides to generate free fatty acids and cholesterol in the cell. The downstream metabolites of these compounds serve as hormonal ligands for nuclear receptors and transcription factors. Genetic ablation of the lal gene in the mouse caused malformation of macrophages and inflammation-triggered multiple pathogenic phenotypes in multiple organs. To assess the relationship between macrophages and lal-/- pathogenic phenotypes, a macrophage-specific doxycycline-inducible transgenic system was generated to induce human LAL (hLAL) expression in the lal-/- genetic background under control of the 7.2-kb c-fms promoter/intron2 regulatory sequence. Doxycycline-induced hLAL expression in macrophages significantly ameliorated aberrant gene expression, inflammatory cell (neutrophil) influx, and pathogenesis in multiple organs. These studies strongly support that neutral lipid metabolism in macrophages contributes to organ inflammation and pathogenesis.

Animals↗

[Genetic polymorphisms of 10 X chromosome STR loci in a Chinese Tibetan population].

OBJECTIVE: To investigate the alleles and genotypes frequency of 10 short tandem repeat (STR) loci on the X chromosome(DXS7423, DXS8378, DXS6799, DXS7424, DXS7130, DXS7132, DXS6789, DXS101, DXS6804, DXS7133) of Tibetan individuals living in Xizang Autonomous Region, Southwest China. METHODS: The 10 X-chromosomal STR loci were analyzed with PCR, followed by polyacylamide gel electrophoresis and silver staining. RESULTS: Among unrelated Tibetan individuals, the numbers of alleles in the 10 X-STR loci(DXS7423, DXS8378, DXS6799, DXS7424, DXS7130, DXS7132, DXS6789, DXS101, DXS6804, DXS7133) were 5, 5, 5, 9, 7, 7, 11, 9, 5 and 4, respectively. The genotype frequencies in females were in accordance with Hardy-Weinberg equilibrium. CONCLUSION: The 10 X-chromosomal STRs loci are appropriate for individual identification, for paternity testing involving a female child, and for studies on related disease.

Asian People↗

[Analysis of the multi-amplified 5 STR loci and their allelic distribution in both Han populations in Chengdu City and Yunnan province].

OBJECTIVE: To illuminate the multi-amplified 5 STR loci and their allelic distribution in Hans by means of STR-DNA typing with improved efficiency and decreased cost. METHODS: We have established an allelic ladder of D7S820, D13S317, D5S818, D3S1358 and Amelogenin loci via the cloning techniques. With this homemade allelic ladder, we established successfully a multiplexing polymerase chain reaction (PCR) method, followed by denaturing polyacrylamide gel electrophoresis (PAGE) and silver staining. DNA samples collected from 130 unrelated Han individuals in Yunnan and Chengdu were analyzed. The non-overlapping of the allelic fragments of the five loci allowed the detection to be accomplished successfully. RESULTS: No difference of the genotyping results of the single locus amplification and multiplexing was observed. The genotype distributions of 4 STR were in accordance with the Hardy-Weinberg equilibrium. 7, 7, 8 and 8 alleles of D7S820, D13S317, D5S818, and D3S1358 loci were observed in Yunnan Han population, as well as 8, 7, 8 and 7 alleles in Chengdu Han population respectively. No significant difference in the allele distribution of these loci was seen between these two Han populations. CONCLUSION: This multiplexing system with home-made allelic ladder has a high combined discrimination power and exclusion power. It is a valuable tool in forensic science practice.

Alleles↗

[A minisequencing technique for genotyping 12 Y-SNP and its genetic polymorphisms].

OBJECTIVE: The aim of the present study was to establish a rapid and robust assay used to simultaneously genotype SNPs by the single nucleotide primer extension (minisequencing) with the SNaPshot Kit and obtain the population genetic data in Chinese population in Sichuan. The analysis of single nucleotide polymorphisms (SNPs) is a promising application in forensic casework. METHODS: 12 Y-SNPs, which were SRY2627, SRY1532, M13, M20, SRY8299, Tat, M69, M9, 92R7, M17, M19 and M112, were multiple amplificated and the PCR products were pooled, Purified, and then used as templates for the minisequencing reaction with the commol/Lercially available SNaPshot Kit. Then the products of minisequencing reaction were detected by capillary elcetrophoresis. RESULTS: 78 genomic DNA individual samples from Sichuan, China and 5 semen stain samples from sexal criminal scene were analyzed and two haplotypes could be identified. CONCLUSION: A rapid method has been established to analyze the 12 Y-SNPs by multiplex PCR and minisequencing. It can be applied in forensic casework successfully.

Base Sequence↗

The role of mannosylated enzyme and the mannose receptor in enzyme replacement therapy.

Lysosomal acid lipase (LAL) is the critical enzyme for the hydrolysis of triglycerides (TGs) and cholesteryl esters (CEs) in lysosomes. LAL defects cause Wolman disease (WD) and CE storage disease (CESD). An LAL null (lal-/-) mouse model closely mimics human WD/CESD, with hepatocellular, Kupffer cell and other macrophage, and adrenal cortical storage of CEs and TGs. The effect on the cellular targeting of high-mannose and complex oligosaccharide-type oligosaccharide chains was tested with human LAL expressed in Pichia pastoris (phLAL) and CHO cells (chLAL), respectively. Only chLAL was internalized by cultured fibroblasts, whereas both chLAL and phLAL were taken up by macrophage mannose receptor (MMR)-positive J774E cells. After intraperitoneal injection into lal-/- mice, phLAL and chLAL distributed to macrophages and macrophage-derived cells of various organs. chLAL was also detected in hepatocytes. Ten injections of either enzyme over 30 d into 2- and 2.5-mo-old lal-/- mice produced normalization of hepatic color, decreased liver weight (50%-58%), and diminished hepatic cholesterol and TG storage. Lipid accumulations in macrophages were diminished with either enzyme. Only chLAL cleared lipids in hepatocytes. Mice double homozygous for the LAL and MMR deficiences (lal-/-;MMR-/-) showed phLAL uptake into Kupffer cells and hepatocytes, reversal of macrophage histopathology and lipid storage in all tissues, and clearance of hepatocytes. These results implicate MMR-independent and mannose 6-phosphate receptor-independent pathways in phLAL uptake and delivery to lysosomes in vivo. In addition, these studies show specific cellular targeting and physiologic effects of differentially oligosaccharide-modified human LALs mediated by MMR and that lysosomal targeting of mannose-terminated glycoproteins occurs and storage can be eliminated effectively without MMR.

Animals↗

Transcriptional regulation of phagocytosis-induced membrane biogenesis by sterol regulatory element binding proteins.

In the process of membrane biogenesis several dozen proteins must operate in precise concert to generate approximately 100 lipids at appropriate concentrations. To study the regulation of bilayer assembly in a cell cycle-independent manner, we have exploited the fact that phagocytes replenish membranes expended during particle engulfment in a rapid phase of lipid synthesis. In response to phagocytosis of latex beads, human embryonic kidney 293 cells synthesized cholesterol and phospholipids at amounts equivalent to the surface area of the internalized particles. Lipid synthesis was accompanied by increased transcription of several lipogenic proteins, including the low-density lipoprotein receptor, enzymes required for cholesterol synthesis (3-hydroxy-3-methylglutaryl CoA synthase, 3-hydroxy-3-methylglutaryl CoA reductase), and fatty acid synthase. Phagocytosis triggered the proteolytic activation of two lipogenic transcription factors, sterol regulatory element binding protein-1a (SREBP-1a) and SREBP-2. Proteolysis of SREBPs coincided with the appearance of their transcriptionally active N termini in the nucleus and 3-fold activation of an SREBP-specific reporter gene. In previous studies with cultured cells, proteolytic activation of SREBP-1a and SREBP-2 has been observed in response to selective starvation of cells for cholesterol and unsaturated fatty acids. However, under the current conditions, SREBP-1a and SREBP-2 are induced without lipid deprivation. SREBP activation is inhibited by high levels of the SREBP-interacting proteins Insig1 or the cytosolic domain of SREBP cleavage-activating protein. Upon overexpression of these proteins, phagocytosis-induced transcription and lipid synthesis were blocked. These results identify SREBPs as essential regulators of membrane biogenesis and provide a useful system for further studies on membrane homeostasis.

CCAAT-Enhancer-Binding Proteins↗

Systematic investigation of the signal properties of polycrystalline HgI2 detectors under mammographic, radiographic, fluoroscopic and radiotherapy irradiation conditions.

The signal properties of polycrystalline mercuric iodide (HgI2) film detectors, under irradiation conditions relevant to mammographic, radiographic, fluoroscopic and radiotherapy x-ray imaging, are reported. Each film detector consists of an approximately 230 to approximately 460 microm thick layer of HgI2 (fabricated through physical vapour deposition or a screen-print process) and a thin barrier layer, sandwiched between a pair of opposing electrode plates. The high atomic number, high density and low effective ionization energy, W(EFF), of HgI2 make it an attractive candidate for significantly improving the performance of active matrix, flat-panel imagers (AMFPIs) for several x-ray imaging applications. The temporal behaviour of current from the film detectors in the presence and in the absence of radiation was used to examine dark current levels, the lag and reciprocity of the signal response, x-ray sensitivity and W(EFF). The results are discussed in the context of present AMFPI performance. This study provides performance data for a wide range of potential medical x-ray imaging applications from a single set of detectors and represents the first investigation of the signal properties of polycrystalline mercuric iodide for the radiotherapy application.

Crystallization↗

Overexpression of Stat3C in pulmonary epithelium protects against hyperoxic lung injury.

Acute lung injury is a side effect of therapy with a high concentration of inspired oxygen in patients. The molecular mechanism underlining this effect is poorly understood. In this study, we report that overexpression of Stat3C, a constitutive active form of STAT3, in respiratory epithelial cells of a doxycycline-controlled double-transgenic mouse system protects lung from inflammation and injury caused by hyperoxia. In this mouse line, >50% of transgenic mice survived exposure to 95% oxygen at day 7, compared with 0% survival of wild-type mice. Overexpression of STAT3C delays acute capillary leakage and neutrophil infiltration into the alveolar region. This protection is mediated at least partially through inhibition of hyperoxia-induced synthesis and release of matrix metalloproteinase (MMP)-9 and MMP-12 by neutrophils and alveolar resident cells. In some MMP-9(-/-) mice, prolonged survival was observed under hyperoxic condition. The finding supports a concept that activation of the Stat3 pathway plays a role to prevent hyperoxia-induced inflammation and injury in the lung.

Acute-Phase Proteins↗

Neutral lipids and peroxisome proliferator-activated receptor-{gamma} control pulmonary gene expression and inflammation-triggered pathogenesis in lysosomal acid lipase knockout mice.

The functional roles of neutral lipids in the lung are poorly understood. However, blocking cholesteryl ester and triglyceride metabolism in lysosomal acid lipase gene knockout mice (lal-/-) results in severe pathogenic phenotypes in the lung, including massive neutrophil infiltration, foamy macrophage accumulation, unwanted cell growth, and emphysema. To elucidate the mechanism underlining these pathologies, we performed Affymetrix GeneChip microarray analysis of 1-, 3-, and 6-month-old mice and identified aberrant gene expression that progressed with age. Among changed genes, matrix metalloproteinase (MMP)-12, apoptosis inhibitor 6 (Api-6), erythroblast transformation-specific domain (Ets) transcription factor family member Spi-C, and oncogene MafB were increased 100-, 70-, 40-, and 10-fold, respectively, in lal-/- lungs versus the wild-type lungs. The pathogenic increases of these molecules occurred primarily in alveolar type II epithelial cells. Transcriptional activities of the MMP-12 and Api-6 promoters were stimulated by Spi-C or MafB in respiratory epithelial cells. Treatment with 9-hydroxyoctadecanoic acids and ciglitazone significantly rescued lal-/- pulmonary inflammation and aberrant gene expression. In addition, both compounds as well as peroxisome proliferator-activated receptor gamma inhibited MMP-12 and Api-6 promoter activities. These data suggest that inflammation-triggered cell growth and emphysema during lysosomal acid lipase deficiency are partially caused by peroxisome proliferator-activated receptor-gamma inactivation.

Animals↗

Segmented phosphors: MEMS-based high quantum efficiency detectors for megavoltage x-ray imaging.

Current electronic portal imaging devices (EPIDs) based on active matrix flat panel imager (AMFPI) technology use a metal plate+phosphor screen combination for x-ray conversion. As a result, these devices face a severe trade-off between x-ray quantum efficiency (QE) and spatial resolution, thus, significantly limiting their imaging performance. In this work, we present a novel detector design for indirect detection-based AMFPI EPIDs that aims to circumvent this trade-off. The detectors were developed using micro-electro-mechanical system (MEMS)-based fabrication techniques and consist of a grid of up to approximately 2 mm tall, optically isolated cells of a photoresist material, SU-8. The cells are dimensionally matched to the pixels of the AMFPI array, and packed with a scintillating phosphor. In this paper, various design considerations for such detectors are examined. An empirical evaluation of three small-area (approximately 7 x 7 cm2) prototype detectors is performed in order to study the effects of two design parameters--cell height and phosphor packing density, both of which are important determinants of the imaging performance. Measurements of the x-ray sensitivity, modulation transfer function (MTF) and noise power spectrum (NPS) were performed under radiotherapy conditions (6 MV), and the detective quantum efficiency (DQE) was determined for each prototype SU-8 detector. In addition, theoretical calculations using Monte Carlo simulations were performed to determine the QE of each detector, as well as the inherent spatial resolution due to the spread of absorbed energy. The results of the present studies were compared with corresponding measurements published in an earlier study using a Lanex Fast-B phosphor screen coupled to an indirect detection array of the same design. The SU-8 detectors exhibit up to 3 times higher QE, while achieving spatial resolution comparable or superior to Lanex Fast-B. However, the DQE performance of these early prototypes is significantly lower than expected due to high levels of optical Swank noise. Consequently, the SU-8 detectors presently exhibit DQE values comparable to Lanex Fast-B at zero spatial frequency and significantly lower than Fast-B at higher frequencies. Finally, strategies for reducing Swank noise are discussed and theoretical calculations, based on the cascaded systems model, are presented in order to estimate the performance improvement that can be achieved through such noise reduction.

Computer-Aided Design↗

Segmented crystalline scintillators: an initial investigation of high quantum efficiency detectors for megavoltage x-ray imaging.

Electronic portal imaging devices (EPIDs) based on indirect detection, active matrix flat panel imagers (AMFPIs) have become the technology of choice for geometric verification of patient localization and dose delivery in external beam radiotherapy. However, current AMFPI EPIDs, which are based on powdered-phosphor screens, make use of only approximately 2% of the incident radiation, thus severely limiting their imaging performance as quantified by the detective quantum efficiency (DQE) (approximately 1%, compared to approximately 75% for kilovoltage AMFPIs). With the rapidly increasing adoption of image-guided techniques in virtually every aspect of radiotherapy, there exist strong incentives to develop high-DQE megavoltage x-ray imagers, capable of providing soft-tissue contrast at very low doses in megavoltage tomographic and, potentially, projection imaging. In this work we present a systematic theoretical and preliminary empirical evaluation of a promising, high-quantum-efficiency, megavoltage x-ray detector design based on a two-dimensional matrix of thick, optically isolated, crystalline scintillator elements. The detector is coupled with an indirect detection-based active matrix array, with the center-to-center spacing of the crystalline elements chosen to match the pitch of the underlying array pixels. Such a design enables the utilization of a significantly larger fraction of the incident radiation (up to 80% for a 6 MV beam), through increases in the thickness of the crystalline elements, without loss of spatial resolution due to the spread of optical photons. Radiation damage studies were performed on test samples of two candidate scintillator materials, CsI(Tl) and BGO, under conditions relevant to radiotherapy imaging. A detailed Monte Carlo-based study was performed in order to examine the signal, spatial spreading, and noise properties of the absorbed energy for several segmented detector configurations. Parameters studied included scintillator material, septal wall material, detector thickness, and the thickness of the septal walls. The results of the Monte Carlo simulations were used to estimate the upper limits of the modulation transfer function, noise power spectrum and the DQE for a select number of configurations. An exploratory, small-area prototype segmented detector was fabricated by infusing crystalline CsI(Tl) in a 2 mm thick tungsten matrix, and the signal response was measured under radiotherapy imaging conditions. Results from the radiation damage studies showed that both CsI(Tl) and BGO exhibited less than approximately 15% reduction in light output after 2500 cGy equivalent dose. The prototype CsI(Tl) segmented detector exhibited high uniformity, but a lower-than-expected magnitude of signal response. Finally, results from Monte Carlo studies strongly indicate that high scintillator-fill-factor configurations, incorporating high-density scintillator and septal wall materials, could achieve up to 50 times higher DQE compared to current AMFPI EPIDs.

Computer Simulation↗

MRI of fat distribution in a mouse model of lysosomal acid lipase deficiency.

OBJECTIVE: We assessed the use of MRI in the evaluation of abdominal fat distribution in a lysosomal acid lipase (LAL)-deficient mouse model. MATERIALS AND METHODS: LAL-deficient mice are born with a normal fat distribution but over time deplete the fat stores in the subcutaneous and retroperitoneal tissues and accumulate fat in the liver, spleen, and bowel. Four MRI studies of LAL-deficient mice and control mice were obtained with 3-T T1-weighted spin-echo images and volume segmentation processing to create parameters for the study of fat distribution: intraabdominal adipose tissue-subcutaneous adipose tissue (IAT/SAT) ratio, liver volume, reproductive fat, and retroperitoneal fat. MRI adiposity parameters in LAL-deficient mice were compared with those in control mice. Adiposity volumes calculated on MRI were compared with those calculated at autopsy. RESULTS: Statistically significant differences were found between LAL-deficient and control mice for IAT/SAT ratio (p=0.0336), liver volume (p=0.0336), and reproductive fat (p=0.0336), and a statistically significant trend was found for retroperitoneal fat (p=0.0514). No statistically significant difference was found between adiposity volumes calculated on MRI and adiposity volumes found at autopsy (all p >0.2). CONCLUSION: Use of an in vivo model showed MRI techniques to be accurate in predicting visceral adiposity. LAL-deficient mice provided a unique model showing a pattern of adipose distribution that is markedly different from that in control mice, and MRI may provide a means of evaluating therapeutic interventions sequentially.

Abdomen↗

[Experiment study on real-time controlling rules of A/O nitrogen removal process].

The aim of this work is operational optimization of an A/O process in the lab plant with synthetic wastewater for improving nitrogen removal efficiency. Ammonia control aims at maintaining the required concentration of ammonia in the effluent by manipulating the dissolved oxygen (DO) set point and aeration volumes. Nitrate control aims at the optimal use of the denitrification potential at any moment by continuously adjusting the internal recirculation flow or (and) external carbon addition flow in order to maintain a desired nitrate set point in the anoxic zone. The control strategies have been based on a hierarchical structure where a high level or supervisory control selects the set point of the low level or conventional controllers. Results indicated that it was possible to increase nitrogen removal efficiency, improve the effluent water quality, save energy, and reduce operating costs.

Ammonia↗

[Transpupillary thermotherapy for circumscribed choroidal hemangioma].

OBJECTIVE: To evaluate the efficacy of transpupillary thermotherapy (TTT) on circumscribed choroidal hemangioma. METHODS: Ten eyes of 10 cases with circumscribed choroidal hemangioma (age 16-48, average 34.4) were included in the present study. Six cases had previous green laser (4 argon and 2 krypton) photocoagulation, TTT as a primary treatment was used for other 4 cases without previous laser application. Fluorescein angiography, visual acuity, anterior segment and fundus examination, perimetry test, FFA/ICGA and ultrasonography were performed in all patients before the treatment. One to five infra red diode laser spots (810 nm with power of 800-1200 mW, diameter of 3 mm) were delivered on the surface of tumor with 60 seconds exposure, additional 10-20 seconds exposure was used in some cases. Second treatment was given 1-3 month later if there was active leakage demonstrated by fluorescein angiography. The followed-up period was 6-36 months (averaged 14.5 month). RESULTS: After transpupillary thermotherapy, 9 eyes (90%) showed partial regression of the tumor. Average visual acuity was 0.25 and 0.6 before and after TTT, respectively. Six patients showed improvement of vision acuity, but vision acuity in 4 patients with cystic macular degeneration remained unchanged. No recurrences were observed within follow-up averaged 14.5 months. Transpupillary thermotherapy did not associate with any significant complications. CONCLUSION: Transpupillary thermotherapy is effective to treat circumscribed hemangioma of choroid either as a primary treatment or supplementary therapy to previous laser photocoagulation.

Adolescent↗