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Biomedical subjects

Q Zeng

Publications and source records attributed to Q Zeng.

At least 37 records · Page 2Linked to original sources

A multicenter, randomized, controlled trial to evaluate the safety profile, tolerability, and efficacy of rofecoxib in advanced elderly patients with osteoarthritis.

This 6-week study was conducted to test the efficacy, safety, and tolerability of rofecoxib (a selective COX-2 inhibitor) compared to nabumetone (a non-selective NSAID) and placebo in osteoarthritis (OA) patients aged 80 and older. Three hundred forty-one patients, mean age 83 years, were randomized. Allocations were made in an approximately 1:2:1:2 ratio (placebo: 12.5 mg rofecoxib: 25 mg rofecoxib: 1500 mg nabumetone). Least square mean changes from baseline in the primary efficacy endpoint, Patient Global Assessment of Disease Status, were as follows (with negative numbers indicating improvement): -14.85 mm for placebo; -25.34 mm for 12.5 mg rofecoxib; -25.40 mm for 25 mg of rofecoxib; and -25.95 mm for nabumetone (p<0.001 for all active treatments vs placebo.) Results from secondary endpoints, including the 3 WOMAC sub-scales (pain, stiffness, and disability) and the Investigator Global Assessment of Disease Status, were consistent with those for the primary endpoint. No significant between-group differences were observed in the proportions of patients who discontinued treatment due to either clinical or laboratory adverse experiences. Renal safety (edema and hypertension adverse experiences) was similar for rofecoxib and nabumetone. No gastroduodenal ulcers occurred; however, the demonstration of gastrointestinal risk with rofecoxib or nabumetone was beyond the scope of this trial. We conclude that in patients 80 years and older, rofecoxib, 12.5 mg and 25 mg once daily, demonstrated clinical efficacy for the treatment for OA as did 1500 mg of nabumetone. Rofecoxib and nabumetone were generally well tolerated in this elderly population.

Aged↗

Fungi and humans: closer than you think.

The budding yeast, Saccharomyces cerevisiae, has long been used as a model system to study the functions of human genes. Now that the genome sequences from several other fungal species are nearly complete, we can characterize the genetic diversity in the fungal kingdom at the genomic level. This diversity means that the number of human genes with homologues in the fungal kingdom is double that with homologues in S. cerevisiae only. Therefore, functional studies of human genes in the fungal model systems should look beyond S. cerevisiae.

Fungal Proteins↗

Regulation of death receptor expression and TRAIL/Apo2L-induced apoptosis by NF-kappaB.

TRAIL (tumour-necrosis factor-related apoptosis ligand or Apo2L) triggers apoptosis through engagement of the death receptors TRAIL-R1 (also known as DR4) and TRAIL-R2 (DR5). Here we show that the c-Rel subunit of the transcription factor NF-kappaB induces expression of TRAIL-R1 and TRAIL-R2; conversely, a transdominant mutant of the inhibitory protein IkappaBalpha or a transactivation-deficient mutant of c-Rel reduces expression of either death receptor. Whereas NF-kappaB promotes death receptor expression, cytokine-mediated activation of the RelA subunit of NF-kappaB also increases expression of the apoptosis inhibitor, Bcl-xL, and protects cells from TRAIL. Inhibition of NF-kappaB by blocking activation of the IkappaB kinase complex reduces Bcl-x L expression and sensitizes tumour cells to TRAIL-induced apoptosis. The ability to induce death receptors or Bcl-xL may explain the dual roles of NF-kappaB as a mediator or inhibitor of cell death during immune and stress responses.

Animals↗

Genome sequence and comparative analysis of the solvent-producing bacterium Clostridium acetobutylicum.

The genome sequence of the solvent-producing bacterium Clostridium acetobutylicum ATCC 824 has been determined by the shotgun approach. The genome consists of a 3.94-Mb chromosome and a 192-kb megaplasmid that contains the majority of genes responsible for solvent production. Comparison of C. acetobutylicum to Bacillus subtilis reveals significant local conservation of gene order, which has not been seen in comparisons of other genomes with similar, or, in some cases closer, phylogenetic proximity. This conservation allows the prediction of many previously undetected operons in both bacteria. However, the C. acetobutylicum genome also contains a significant number of predicted operons that are shared with distantly related bacteria and archaea but not with B. subtilis. Phylogenetic analysis is compatible with the dissemination of such operons by horizontal transfer. The enzymes of the solventogenesis pathway and of the cellulosome of C. acetobutylicum comprise a new set of metabolic capacities not previously represented in the collection of complete genomes. These enzymes show a complex pattern of evolutionary affinities, emphasizing the role of lateral gene exchange in the evolution of the unique metabolic profile of the bacterium. Many of the sporulation genes identified in B. subtilis are missing in C. acetobutylicum, which suggests major differences in the sporulation process. Thus, comparative analysis reveals both significant conservation of the genome organization and pronounced differences in many systems that reflect unique adaptive strategies of the two gram-positive bacteria.

Amino Acid Sequence↗

Catabolic effects of continuous human PTH (1--38) in vivo is associated with sustained stimulation of RANKL and inhibition of osteoprotegerin and gene-associated bone formation.

Continuous infusion of PTH in vivo results in active bone resorption. To investigate the molecular basis of the catabolic effect of PTH in vivo, we evaluated the role of OPG and RANKL, which are known to influence osteoclast formation and function. Weanling rats fed a calcium-free diet were parathyroidectomized and infused with PTH via an Alzet pump to examine: 1) the changes of serum-ionized calcium and osteoclast number, 2) the expression of OPG/RANKL mRNA and protein, and 3) the expression of osteoblast phenotype bone formation-associated genes such as osteoblast specific transcription factor, osteocalcin, bone sialoprotein, and type I collagen. PTH (1--38) (0.01--20 microg/100 g) continuous infusion for 1--24 h resulted in a dose-dependent increase in serum-ionized calcium in parathyroidectomized rats and a corresponding dose-dependent increase in osteoclast number, indicating an increased bone resorption. At 20 microg/100 g PTH dose level, serum-ionized calcium was 2.1-fold of the vehicle control and not different from the Sham-parathyroidectomized rats, and osteoclast number was 3-fold of the vehicle control and 1.7-fold of the Sham-parathyroidectomized rats. In the distal femur, RANKL mRNA expression was increased (27-fold) and OPG mRNA expression was decreased (4.6-fold). The changes in RANKL and OPG mRNA levels were rapid (as early as 1 h), dose dependent, and sustained over a 24-h period that was examined. Immunohistochemical evaluation of bone sections confirmed that OPG level was reduced in proximal tibial metaphysis upon PTH infusion. Circulating OPG protein level was also decreased by 32% when compared with the parathyroidectomized control. The expression of genes that mark the osteoblast phenotype was significantly decreased [osteoblast specific transcription factor (2.3-fold), osteocalcin (3-fold), bone sialoprotein (2.8-fold), and type I collagen (5-fold)]. These results suggest that the catabolic effect of PTH infusion in vivo in this well-established resorption model is associated with a reciprocal expression of OPG/RANKL and a co-ordinate decrease in the expression of bone formation-related genes. We propose that the rapid and sustained increase in RANKL and decrease in OPG initiate maintain and favor the cascade of events in the differentiation/recruitment and activation of osteoclasts.

Animals↗

[Malformed macrocephalous sperm with polytails and chromosomal aberrance].

OBJECTIVE: To investigate the relationship between sperm anomalies and chromosomal aberrance and to further understand the pathological changes of anomalous spermatozoa. METHODS: Light and electronic (SEM or TEM) microscopes were used for morphological analysis. Fluorescence in situ hybridization(FISH) with chromosome X-, Y-specific probes were used for aneuploidy detection in sperms of the patient. RESULTS: Ninety eight point seven five per cent of the Papanicolaou stained sperms were observed to be abnormal; 100% of the sperm heads were abnormal, measured under oil objective (1000 times); 60.25% of the sperms had two or more tails (the maximum being eight tails). SEM and TEM demonstrated that the heads contained a large amount of cytoplasmic structure, the surfaces of heads were uneven, the nuclei were of much irregular shape; besides aberrance in quantity, anomalies occurred with centromeres, mitochondria and flagella in the tails. The results of FISH showed that the aneuploidy rate of sex chromosomes was 61.41% which was parallel to the rate of polytails. CONCLUSION: Even though the chromosomes in somatic cells are normal, the chromosomes in anomalous sperms may be abnormal.

Adult↗

[Study on frequencies of aneuploidy in mouse oocyte and female pronucleus of one cell zygote induced by benzene].

OBJECTIVE: To study the effect of benzene on aneupoidy of oocytes and female pronucleus of one cell zygotes. METHOD: The NIH adult female mice were treated with varies doses of benzene (942, 1,881 and 3,762 mg/kg respectively) via single gavage and (706, 1,922 and 4,864 mg/m3, respectively) multiple inhalation. After gavage, the mice were pair-matched (1:1) with males overnight. The ovulated oocytes and the one cell zygotes were collected for cytogenetic analysis and the frequencies of aneuploidy were detected. RESULTS: The frequencies of aneuploid in M II oocytes significantly increased in the three groups treated with inhalation (7.06%, 7.50% and 7.76%, respectively, control group 0.00%, P < 0.05) of benzene, as compared with those in the control group (1.30%), with a dose-dependent response. Meiotic delay of M I oocytes was observed, with the frequency of M I oocytes of 1.16%, 3.61% and 5.75%, respectively, P < 0.05, in a dose-dependent response, too. In gavage treatment group, increase in frequency of M II oocyte aneuploidy was only observed in the high-dose group, and aneupliody frequency of female pronucleus in one cell zygotes was not induced. CONCLUSION: Exposure to high-dose benzene via gavage or inhalation was able to induce increase in aneuploidy frequency of M II oocytes in mice.

Aneuploidy↗

[Does response of rape to La and critical concentration of La in red earth].

The effects of different concentration of La added in red soil on the growth, yield, content of chlorophyll and peroxidase(POD) activity of rape were studied by pot experiments. The results showed that the growth and yield of rape could be improved by low concentration of La3+, however there was no significant difference between the treatment and the control, and inhibited when the dose were more than 300 mg kg-1 and killed after 600 mg.kg-1 La was added. The decrease of chlorophyll content and chlorophyll a/b was observed when the exogenous concentration of La was more than 15 mg.kg-1. POD activity increased gradually with increasing concentration and prolonging reaction. The feasible application level of La was suggested to be below 15 mg.kg-1.

Chlorophyll↗

Patient and clinician vocabulary: how different are they?

Consumers and patients are confronted with a plethora of health care information, especially through the proliferation of web content resources. Democratization of the web is an important milestone for patients and consumers since it helps to empower them, make them better advocates on their own behalf and foster better, more-informed decisions about their health. Yet lack of familiarity with medical vocabulary is a major problem for patients in accessing the available information. As a first step to providing better vocabulary support for patients, this study collected and analyzed patient and clinician terms to confirm and quantitatively assess their differences. We also analyzed the information retrieval (IR) performance resulting from these terms. The results showed that patient terminology does differ from clinician terminology in many respects including misspelling rate, mapping rate and semantic type distribution, and patient terms lead to poorer results in information retrieval.

Humans↗

[An epidemiological and clinical study of primary gout].

OBJECTIVE: To evaluate the prevalence of primary gout in Shantou and Beijing area, and understand it's clinical features. METHODS: Three epidemiological studies in Chenghai downtown, and the one of study in Beijing were studied. Clinical, laboratory and radiology data were collected and analyzed. RESULT: The prevalence of primary gout in Chenghai surveys was 0.17%, 0.15% and 0.26% respectively; no case of primary gout was found in Beijing survey. Among the patients, male to female ratio was 21:1; average onset age of females was significantly higher than that of males. The numbers of patient in the recent 10 years was increasing. At the first attack, the first metatarsophalangeal joint was involved among 79.7% of all cases; no fourth metatarsophalangeal joint involvement had been found. Hyperlipemia was the most common accompanying abnormal laboratory test (57.1%). Radiographic bone erosion was found in 49.4% patients, most of them, the duration of disease was over 5 years. CONCLUSION: The prevalence of primary gout was higher in Shantou area than that in Beijing, and it was increasing in the recent 10 years in Shantou area. The difference of geography, climate, food and lifestyle could be responsible for the different prevalence in different area.

Adult↗

[Effects of radiofrequency catheter ablation in coagulation system].

OBJECTIVE: To investigate the pathogenesis and prophylactic therapy of peripheral vascular embolism after radiofrequency catheter ablation (RFCA). METHOD: 90 patients with supraventricular tachycardia (SVT) were divided into 3 groups. Group A did not use any anticoagulant before RFCA and group B used aspirin (ASA) before RFCA, group C used calcium channel blocker-amlodipine before RFCA. Blood samples were taken at 4 time points, i.e. before and after electrophysiologic examination, immediately after RFCA and 2 days after RFCA. For each blood example, blood levels of platelet alpha-granule membrane glycoprotein-140 (Gmp-140), thromboxane B(2) (TXB(2)), protein C (PC), protein S (PS) were measured. RESULT: In group A, Gmp-140 and TXB(2) of the blood examples taken before electrophysiologic examination were significantly lower than those taken at the three other time points, but there was no significant change of PC and PS as compared with that at the three other time points. Ablation either on the left or right heart did not affect the levels of Gmp-140 and TXB(2); In group B and group C, the levels of Gmp-140 and TXB(2) of the samples were significantly lower than those of the corresponding points in group A. CONCLUSION: It is indicated that platelet aggregability may be introduced by RFCA, but evolution of the anticoagulant system was not caused by RFCA, This may enhance the occurrence of thrombosis. ASA and amlodipine may prevent the occurrence of thrombosis.

Adolescent↗

Finding appropriate clinical trials: evaluating encoded eligibility criteria with incomplete data.

We describe our work on creating a system that selects appropriate clinical trials by automating the evaluation of eligibility criteria. We developed a data model of eligibility for breast cancer clinical trials, upon which the criteria were encoded. Standard vocabularies are utilized to represent concepts used in the system, and retrieve their hierarchical relationships. The system incorporates Bayesian networks to handle missing patient information. Protocols are ranked by the belief that the patient is eligible for each of them. In a preliminary evaluation, we found good agreement (kappa 0.86) between the system and an independent physician in selection of protocols, but poor agreement (kappa 0.24) in protocol ranking. We conclude that our approach is feasible, and potentially useful in assisting both physicians and patients in the task of selecting appropriate trials.

Bayes Theorem↗

Problems and challenges in patient information retrieval: a descriptive study.

Many patients now turn to the Web for health care information. However, a lack of domain knowledge and unfamiliarity with medical vocabulary and concepts restrict their ability to successfully obtain information they seek. The purpose of this descriptive study was to identify and classify the problems a patient encounters while performing information retrieval tasks on the Web, and the challenges it poses to informatics research. In this study, we observed patients performing various retrieval tasks, and measured the effectiveness of, satisfaction with, and usefulness of the results. Our study showed that patient information retrieval often failed to produce successful results due to a variety of problems. We propose a classification of patient IR problems based on our observations.

Adult↗

Using features of Arden Syntax with object-oriented medical data models for guideline modeling.

Computer-interpretable guidelines (CIGs) can deliver patient-specific decision support at the point of care. CIGs base their recommendations on eligibility and decision criteria that relate medical concepts to patient data. CIG models use expression languages for specifying these criteria, and define models for medical data to which the expressions can refer. In developing version 3 of the GuideLine Interchange Format (GLIF3), we used existing standards as the medical data model and expression language. We investigated the object-oriented HL7 Reference Information Model (RIM) as a default data model. We developed an expression language, called GEL, based on Arden Syntax's logic grammar. Together with other GLIF constructs, GEL reconciles incompatibilities between the data models of Arden Syntax and the HL7 RIM. These incompatibilities include Arden's lack of support for complex data types and time intervals, and the mismatch between Arden's single primary time and multiple time attributes of the HL7 RIM.

Decision Making, Computer-Assisted↗

Molecular identification using flow cytometry histograms and information theory.

Flow cytometry is a common technique for quantitatively measuring the expression of individual molecules on cells. The molecular expression is represented by a frequency histogram of fluorescence intensity. For flow cytometry to be used as a knowledge discovery tool to identify unknown molecules, histogram comparison is a major limitation. Many traditional comparison methods do not provide adequate assessment of histogram similarity and molecular relatedness. We have explored a new approach applying information theory to histogram comparison, and tested it with histograms from 14 antibodies over 3 cell types. The information theory approach was able to improve over traditional methods by recognizing various non-random correlations between histograms in addition to similarity and providing a quantitative assessment of similarity beyond hypothesis testing of identity.

Animals↗

Design and synthesis of fluoroquinophenoxazines that interact with human telomeric G-quadruplexes and their biological effects.

In this study we have identified a new structural motif for a ligand with G-quadruplex interaction that results in biological effects associated with G-quadruplex-interactive compounds. Fluoroquinolones have been reported to possess weak telomerase inhibitory activity in addition to their better known bacterial gyrase poisoning. Starting with a fluoroquinobenzoxazine, which has modest potency in a human topoisomerase II assay, we have designed a more potent inhibitor of telomerase that has lost its topoisomerase II poisoning activity. This fluoroquinophenoxazine (FQP) interacts with G-quadruplex structures to inhibit the progression of Taq polymerase in a G-quadruplex polymerase stop assay. In addition, we demonstrate by 1H NMR studies that this compound interacts with telomeric G-quadruplex structures by external stacking to the G-tetrad with both the unimolecular fold-over and the parallel G-quadruplex structures. A photocleavage assay confirms the FQP interaction site, which is located off center of the external tetrad but within the loop region. Molecular modeling using simulated annealing was performed on the FQP-parallel G-quadruplex complex to determine the optimum FQP orientation and key molecular interactions with the telomeric G-quadruplex structure. On the basis of the results of these studies, two additional FQP analogues were synthesized, which were designed to test the importance of these key interactions. These analogues were evaluated in the Taq polymerase stop assay for G-quadruplex interaction. The data from this study and the biological evaluation of these three FQPs, using cytotoxicity and a sea urchin embryo system, were in accord with the predicted more potent telomeric G-quadruplex interactions of the initial lead compound and one of the analogues. On the basis of these structural and biological studies, the design of more potent and selective telomeric G-quadruplex-interactive compounds can be envisaged.

Animals↗