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Biomedical subjects

Qing Li

Publications and source records attributed to Qing Li.

At least 145 records · Page 8Linked to original sources
PubMed2004

[Relationship between the prevalence of microalbuminuria and components of metabolic syndrome in Shanghai].

OBJECTIVE: To study the relationship between the prevalence of microalbuminuria and components of metabolic syndrome in Shanghai. METHODS: A total of 3532 Shanghai Chinese (men 1622, women 1910) aged over 20 years were included. Body mass index (BMI), blood pressure, fasting plasma glucose, lipid profile and plasma insulin concentrations were measured in all subjects. Oral glucose tolerance test was performed in those subjects without knowing the diabetic history. Urinary albumin-to-creatinine ratio (ACR) was measured in an early morning spot urine sample. Microalbuminuria was diagnosed when ACR was between 30 and 300 mg/g. RESULTS: (1) The prevalence of microalbuminuria was increasing with aging (P < 0.001). When compared with subjects having normal ACR, the waist-hip ratio, systolic and diastolic pressure, serum triglyceride level, fasting plasma glucose and homeostasis model assessment-insulin resistance (HOMA-IR) were all significantly increased in those subjects with microalbuminuria. (2) Along with the increment of number of items on metabolic disorders, the prevalence of microalbuminuria was significantly increased (P for trend < 0.001). (3) Multiple logistic regression analyses revealed that hypertension and hyperglycemia were independent factors associated with microalbuminuria (OR = 2.15, P < 0.001 and OR = 1.64, P = 0.01 respectively). Those subjects with two or more items on metabolic disorders had higher odd ratio for the development of microalbuminuria (OR = 3.93 and 4.77, both P < 0.001) when compared with the subjects without metabolic disorder. CONCLUSION: The prevalence of microalbuminuria was independently associated with hypertension and hyperglycemia. The subjects with multiple metabolic abnormalities had higher risk for the development of microalbuminuria, especially in metabolic syndrome.

Adult↗
PubMed2004

Awareness and attitudes of healthcare professionals in Wuhan, China to the reporting of adverse drug reactions.

BACKGROUND: A voluntary procedure for reporting adverse drug reactions (ADRs) was formally put in place in 1989. However, only a small proportion of ADR reports are actually forwarded to the national monitoring center. To identify the reasons for underreporting, the authors investigated the awareness and attitudes of healthcare professionals (doctors, nurses, and administrators) toward the ADR system in China. In addition, the authors sought to formulate approaches to improve the current ADR reporting system. METHODS: Structured interviews were carried out in 16 hospitals selected from 27 municipal hospitals in Wuhan, Hubei Province, China. A questionnaire survey of a stratified random sample of approximately 15% of healthcare professionals in each selected hospital was conducted during February to March 2003. RESULTS: The response rate of this survey was 85%. One thousand six hundred and fifty-three questionnaires were used in the final analysis. Only 2.7% of the healthcare professionals had a correct understanding to the definition of ADR. Eighty-nine point two percent of the healthcare professionals had encountered ADRs. Ninety-four percent of them were aware of the need to report these to the ADR monitoring center. However, only 28.5% of doctors, 22.8% of nurses, and 29.7% of administrators actually submitted a report. For the most part, they reported ADRs to the hospital pharmacy (66.0%), to other departments in the hospital (72.5%), and to the pharmaceutical industry (23.0%), rather than to the national monitoring center (2.9%) or regional monitoring center (9.5%). Severe or rare ADRs and ADRs to new products were generally perceived to be significant enough to report. Sixty-two point one percent of the healthcare professionals had encountered ADRs, yet not reported them to anybody. The major reasons for not reporting included no knowledge of the reporting procedure (71.4%), unavailability of the reporting center mailing address (67.9%), unavailability of the ADR report form (60.4%), lack of knowledge of the existence of a national ADR reporting system (52.2%), and belief that the ADR in question was already well known (44.1%). CONCLUSIONS: Healthcare professionals in Wuhan, China have little basic knowledge of ADR and of the voluntary reporting system. The main reasons for underreporting were lack of basic knowledge about ADRs and the voluntary reporting procedure. Education and training of healthcare professionals is needed to improve the current ADR reporting system.

Adverse Drug Reaction Reporting Systems↗
PubMed2004

[Re-evaluation of marketed chemical drugs and biological products of therapeutic - a systematic review of literature].

OBJECTIVE: To assess the current status on re-evaluation of marketed drug in China since the promulgation of drug law in 1985. METHODS: Review of literature on Chinese pharmaceutical abstract and CBMdisc from 1985 to 2001 year was done. RESULTS: 4029 papers and 855 marketed drugs from 1985 to 2001 were included. Drugs on anti-infection agent, cardiovascular system and digestive system were the main drugs being re-evaluated, with the proportions of 27.1%, 20.1% and 11.1% respectively. The amounts of both marketed drugs and literature were increasing year by year. The method used for re-evaluation were random and non-random clinical trial. 41.4% of all the samples had a sample size of 50 - 100 research subjects. There were 13 papers with more than 5000 samples. The level on evidence based literature was assessed. 44 papers were graded as first class, and 182 papers the second, 2466 papers the third and 1337 papers the fourth. The quality of literature was improved year by year. CONCLUSION: The amount, quality as well as the sample size of literature being re-evaluated on marketed drug were increased from 1985 to 2001. However, the design and evaluation of those trials were not standardized.

Anti-Infective Agents↗
PubMed2004

[Retrospective analysis of 1905 patients with skin cancer from two general hospitals in western China from 1981 to 2000].

OBJECTIVE: To investigate the clinical features and changes in the incidence of skin cancer in two hospitals located in western China. METHODS: The patients diagnosed pathologically as skin cancer from 1981 to 2000 were retrospectively collected from the two hospitals. Clinical data of patients with skin cancer were collected and analyzed. RESULTS: (1) Of the 1 905 patients with skin cancer, squamous cell carcinoma accounted for 29.4%(560 patients), basal cell carcinoma 28.0% (534), and cutaneous malignant melanoma(CMM) 16.0% (305). (2) There were 591 patients with skin cancer diagnosed between 1980 and 1990, and 1 314 between 1991 and 2000, and accounted for 0.34% and 0.58% of all biopsy cases, respectively. The number of total biopsy patients increased 1.6% every year during the 20 years. The number of biopsy patients with skin cancer and with CMM increased 3.5% and 3.9% every year,respectively. (3) Of the 305 CMM patients, 63.3% located on the acra. These patients were elder, and have a higher rate of trauma and a higher incidence in the male than that in patients with CMM located on the other sites. (4) Of the 305 CMM patients, 64 (21%) had history of trauma at the primary onset sites, and 47 (15.4%) had history of small congenital nevi at the primary sites. CONCLUSION: There are some differences in the clinical features such as location and age between the skin cancer patients in our study and those in white population. The incidence of skin cancer in the two hospitals had been increasing in the 20 years (between 1981 and 2000). Both trauma and small congenital nevi are important risk factors of CMM.

Adult↗
PubMed2004

[Study on the knowledge and attitude to adverse drug reactions reporting among healthcare professionals in Wuhan city].

OBJECTIVE: To investigate the knowledge and attitudes of healthcare professionals (doctors, nurses and administrators) to adverse drug reactions (ADR) in Wuhan city and to identify the reasons for under-reporting. METHODS: Structured interviews were carried out in Wuhan, Hubei province. Questionnaire survey to approximately 15% of the medical practitioners selected from 16 hospitals, was conducted during the period from February to March 2003. RESULTS: Only 2.7% of the interviewees knew the definition of adverse drug reactions. 61.7% of the doctors, 62.7% of the nurses and 61.1% of the administrators had ever encountered an ADR during their practices, but did not report to the national monitoring center or other centers. The major reasons for not reporting included: ignorant about the requirement and the reporting process of ADR (71.4%); address of the reporting agency and Forms unavailable (67.9%, 60.4%); unaware of the existence of a national ADR reporting system (52.2%); needless to report as the ADR being too well known (44.1%). They mainly reported an ADR to the hospital pharmacy or other departments, or to the pharmaceutical administration. Education, training and developing new institutions were ways to improve the reporting system. CONCLUSIONS: Our results showed that healthcare professionals had little knowledge on the basic ADR knowledge. The main reasons for underreporting were related to factors on reporting process, address of related centers and unavailable of the Forms. Education and training to doctors and nurses to enhance the awareness of administrators were the ways to improve the reporting system.

Adverse Drug Reaction Reporting Systems↗
PubMed2003

Detection of point mutations of the Axin1 gene in colorectal cancers.

Axin is a recently identified tumor suppressor that plays an important role in liver and colon cancers. To gain further insights into the structure and function of Axin in controlling cell growth, we analyzed 54 colorectal cancer tissues for mutations in AXIN1 gene. We employed PCR amplification with 23 sets of primers against introns that encompassed the whole coding region of AXIN1 followed by single-strand conformation polymorphism (SSCP) analysis. After subcloning and sequencing analysis of the reamplified DNA from the aberrant bands, we found, in addition to 3 silent mutations, 6 missense point mutations in different functionally important regions. The missense mutation rate is hence 11%, suggesting that Axin deficiency may contribute to the onset of colorectal tumorigenesis.

Adenocarcinoma↗
PubMed2003

Direct regulation of microtubule dynamics by protein kinase CK2.

Microtubule dynamics is essential for many vital cellular processes such as morphogenesis and motility. Protein kinase CK2 is a ubiquitous protein kinase that is involved in diverse cellular functions. CK2 holoenzyme is composed of two catalytic alpha or alpha' subunits and two regulatory beta subunits. We show that the alpha subunit of CK2 binds directly to both microtubules and tubulin heterodimers. CK2 holoenzyme but neither of its individual subunits exhibited a potent effect of inducing microtubule assembly and bundling. Moreover, the polymerized microtubules were strongly stabilized by CK2 against cold-induced depolymerization. Interestingly, the kinase activity of CK2 is not required for its microtubule-assembling and stabilizing function because a kinase-inactive mutant of CK2 displayed the same microtubule-assembling activity as the wild-type protein. Knockdown of CK2alpha/alpha' in cultured cells by RNA interference dramatically destabilized their microtubule networks, and the destabilized microtubules were readily destructed by colchicine at a very low concentration. Further, over-expression of chicken CK2alpha or its kinaseinactive mutant in the endogenous CK2alpha/alpha'-depleted cells fully restored the microtubule resistance to the low dose of colchicine. Taken together, CK2 is a microtubule-associated protein that confers microtubule stability in a phosphorylation-independent manner.

Animals↗
PubMed2003

NADPH diaphorase activity in the rat retina during the early stages of experimental diabetes.

BACKGROUND: Nitric oxide (NO) plays an important physiological role in inter-cellular communication, but when produced in excess it can become toxic. Our goal was to evaluate possible involvement of NO in the development of retinopathy in diabetic rats. METHODS: Diabetes was induced in male albino rats by intravenous injection of streptozotocin. Some of the normal and diabetic rats were raised with added L-arginine to increase in vivo NO synthesis, or with added L-NAME to inhibit the rate of in vivo NO synthesis. NADPH diaphorase histochemistry was conducted on retinal whole mounts and transverse sections at different time intervals after induction of diabetes. The electroretinogram (ERG) was recorded to assess retinal function. RESULTS: After 6 weeks of diabetes, NADPH diaphorase amacrine cells in the diabetic retinas appeared abnormal in their morphology and the degree of staining was decreased in their processes. In contrast, NADPH diaphorase activity was augmented in Müller cells. Supplementing the rats' diet with L-arginine for 10 weeks slightly reduced NADPH diaphorase activity in amacrine cell in normal rats but had no effect on the diabetic rats. Adding L-NAME for 10 weeks did not alter NADPH diaphorase histochemistry in either normal or diabetic rats. The ERG responses were reduced by L-arginine supplementation in normal and diabetic rats, and were unaffected by adding L-NAME to the drinking water. CONCLUSIONS: Our findings are consistent with the hypothesis that high glucose levels are deleterious to the rat retina and that excessive synthesis of NO may contribute to the development of diabetic retinopathy.

Animals↗
PubMed2003

N-Myc downstream-regulated gene 2 (NDRG2) inhibits glioblastoma cell proliferation.

The most severe form of brain glioma, glioblastoma (GBM), is highly malignant and usually resistant to chemotherapy. Therefore, discovery of new targets for gene therapy is important. Using subtraction cloning, we identified the human N-Myc downstream-regulated gene 2 (hNDRG2), located at chromosome 14q11.2, as a gene that is significantly suppressed in GBM tissues. Semiquantitative RT-PCR showed that the hNDRG2 gene transcript is expressed in normal brain tissue and low-grade gliomas but is present at low levels in 15 of 27 (56%) human GBM tissues and all of the 6 human glioblastoma cell lines examined. Furthermore, transfection of human glioblastoma U373 and U138 cells with a cDNA encoding hNDRG2 markedly reduced the cell proliferation. Our findings provide the first evidence to suggest that hNDRG2 may play a role in glioblastoma carcinogenesis.

Apoptosis↗
PubMed2003

Intracellular mediators of granulysin-induced cell death.

Granulysin, a molecule present in the granules of CTL and NK cells, is cytolytic against microbes and tumors. Granulysin induces apoptosis of mammalian cells by damaging mitochondria and causing the release of cytochrome c and apoptosis-inducing factor, resulting in DNA fragmentation. Here we show that Ca2+ and K+ channels as well as reactive oxygen species are involved in granulysin-mediated Jurkat cell death. The Ca2+ channel blockers, nickel and econazole, and the K+ channel blockers, tetraethylammonium chloride, apamin, and charybdotoxin, inhibit the granulysin-induced increase in intracellular Ca2+ ([Ca2+](i)), the decrease in intracellular K+, and apoptosis. Thapsigargin, which releases Ca2+ from the endoplasmic reticulum, prevents a subsequent granulysin-induced increase in [Ca2+](i) in Jurkat cells, indicating that the initial increase in [Ca2+](i) is from intracellular stores. The rise in [Ca2+](i) precedes a decrease in intracellular K+, and elevated extracellular K+ prevents granulysin-mediated cell death. In granulysin-treated cells, electron transport is uncoupled, and reactive oxygen species are generated. Finally, an increase in intracellular glutathione protects target cells from granulysin-induced lysis, indicating the importance of the redox state in granulysin-mediated cell death.

Antigens, Differentiation, T-Lymphocyte↗
PubMed2003

Solution structure and backbone dynamics of the holo form of the frenolicin acyl carrier protein.

During polyketide biosynthesis, acyl carrier proteins (ACPs) perform the central role of transferring polyketide intermediates between active sites of polyketide synthase. The 4'-phosphopantetheine prosthetic group of a holo-ACP is a long and flexible arm that can reach into different active sites and provide a terminal sulfhydryl group for the attachment of acyl groups through a thioester linkage. We have determined the solution structure and characterized backbone dynamics of the holo form of the frenolicin acyl carrier protein (fren holo-ACP) by nuclear magnetic resonance (NMR). Unambiguous assignments were made for 433 hydrogen atoms, 333 carbon atoms, and 84 nitrogen atoms, representing a total of 94.6% of the assignable atoms in this protein. From 879 meaningful NOEs and 45 angle constraints, a family of 24 structures has been calculated. The solution structure is composed of three major alpha-helices packed in a bundle with three additional short helices in intervening loops; one of the short helices slowly exchanges between two conformations. Superposition of the major helical regions on the mean structure yields average atomic rmsd values of 0.49 +/- 0.09 and 0.91 +/- 0.08 A for backbone and non-hydrogen atoms, respectively. Although the three-helix bundle fold is conserved among acyl carrier proteins involved in fatty acid synthases and polyketide synthases, a detailed comparison revealed that ACPs from polyketide biosynthetic pathways are more related to each other in tertiary fold than to their homologues from fatty acid biosynthetic pathways. Comparison of the free form of ACPs (NMR structures of fren ACP and the Bacillus subtilis ACP) with the substrate-bound form of ACP (crystal structure of butyryl-ACP from Escherichia coli) suggests that conformational exchange plays a role in substrate binding.

Acyl Carrier Protein↗
PubMed2003

Intermodular communication in modular polyketide synthases: structural and mutational analysis of linker mediated protein-protein recognition.

Modular polyketide synthases (PKSs) present an attractive scaffold for the engineered biosynthesis of novel polyketide products via recombination of naturally occurring enzyme modules with desired catalytic properties. Recent studies have highlighted the pivotal role of short intermodular "linker pairs" in the selective channeling of biosynthetic intermediates between adjacent PKS modules. Using a combination of computer modeling, NMR spectroscopy, cross-linking, and site-directed mutagenesis, we have investigated the mechanism by which a linker pair from the 6-deoxyerythronolide B synthase promotes chain transfer. Our studies support a "coiled-coil" model in which the individual peptides comprising this linker pair adopt helical conformations that associate through a combination of hydrophobic and electrostatic interactions in an antiparallel fashion. Given the important contribution of such linker pair interactions to the kinetics of chain transfer between PKS modules, the ability to rationally modulate linker pair affinity by site-directed mutagenesis could be useful in the construction of optimized hybrid PKSs.

Amino Acid Sequence↗
PubMed2003

Synthesis and potential antimetastatic activity of monovalent and divalent beta-D-galactopyranosyl-(1-->4)-2-acetamido-2-deoxy-D-glucopyranosides.

Anomers of monovalent and divalent beta-D-galactopyranosyl-(1-->4)-2-acetamido-2-deoxy-D-gluco-pyranosides were synthesized under different glycosylation conditions, and evaluated for in vitro antimetastatic activity. Three compounds showed promising inhibitory effects on cancer cell attachment, spreading, migration, and invasion.

Amino Sugars↗
PubMed2003

Experimental demonstration of the unstirred water layer effect on drug transport in Caco-2 cells.

We previously demonstrated that P-glycoprotein and MRP2 contribute to the secretory transport of grepafloxacin in the small intestine. Although inhibitors of these secretory transporters increased absorptive transport of grepafloxacin, secretory transport was not altered in Caco-2 cells, as determined by a conventional Transwell method. Because the value of the permeability coefficient of grepafloxacin is high, permeation through the unstirred water layer (UL) might be the rate-limiting step. To examine the possibility that the UL effect may mask the involvement of membrane transporters in the transport of drug with high permeability in Caco-2 cells, transport experiments were performed by agitating the experimental solution to decrease the thickness of the UL, and by lowering the temperature to decrease permeation via active transporters. Under these conditions, the UL effect was not rate limiting, and the inhibitory effects of transporter modulators were reflected in the apparent permeability as a decrease in secretory transport as well as an increase in absorptive transport. In conclusion, it was demonstrated that the UL can be the rate-limiting factor for transport of drugs with high membrane permeability in Caco-2 cells. When the UL affects the apparent permeability in an experimental apparatus in vitro, careful analysis is required to evaluate the contributions of transporters from the apparent permeability of drugs.

Biological Transport↗
PubMed2003

Differential expression of CD146 in tissues and endothelial cells derived from infantile haemangioma and normal human skin.

Haemangioma is the most common tumour of endothelial origin, occurring in 4-10% of Caucasian infants. It is characterized by rapid growth during the first year of postnatal life, followed by spontaneous regression from 1 to 7 years of age. The cell surface adhesion molecule CD146 has been identified as an endothelial cell marker. Despite advances in understanding the functional role of CD146 in normal endothelial cells and tumour progression, its expression and a possible role in an endothelial tumour have not been studied. As part of an investigation of endothelial cell alterations in infantile haemangioma, differential expression studies were performed with several known antigens and endothelial cell markers. Using immunohistochemical and flow cytometric analyses, cultured human dermal microvascular endothelial cells isolated from newborn foreskin (HDMEC) were compared with endothelial cells derived from haemangioma tissue (HemECs). In addition, immunohistochemistry was used to compare haemangioma tissues with normal human skin. Unexpectedly, cultured HemECs showed a significantly lower level of CD146 than HDMECs by both flow cytometric analysis and immunofluorescence staining. Using immunohistochemical studies, it was further demonstrated that endothelia in all haemangioma tissues, regardless of the tumour phase, showed negative immunoreactivity for CD146. In contrast, strong positive staining for CD146 was observed in the pericyte-like cells that surround the endothelial layers. These findings are believed to be relevant to the molecular basis of haemangioma. Furthermore, it is possible that antibodies against CD146 may be useful for separating haemangioma-derived endothelial cells from normal endothelial cells and pericytes.

Antigens, CD↗
PubMed2003

Effects of ropivacaine and bupivacaine on rabbit myocardial energetic metabolism and mitochondria oxidation.

To compare the cardiotoxicity induced by ropivacaine and bupivacaine and to investigate the mechanism of cardiotoxicity, 24 mature New Zealand rabbits were divided randomly into control group (group C), ropivacaine group (group R) and bupivacaine group (group B). Hearts were drawn out rapidly from the anesthetized animals and cardiac perfusion was performed immediately. Ropivacaine 500 ng/ml (group R) or bupivacaine 500 ng/ml (group B) was added to the perfusion solution. Ventricular myocardial ATP, ADP and AMP were measured with high performance liquid chromatogram. The ability of myocardial mitochondria oxidation to pyruvate or palmitoylcarnitine was detected with Clark electrode. Our results showed that myocardial ATP and ADP decreased significantly (P < 0.05) in group R and most significantly (P < 0.01) in group B as compared with group C. Myocardial ATP and ADP decreased most significantly (P < 0.01) in group B as compared with group R. The changes of myocardial AMP revealed significant difference among three groups. The changes of pyruvate oxidation exhibited no significant difference among the three groups. Palmitoylcarnitine oxidation decreased markedly (P < 0.05) in group R and most significantly (P < 0.01) in group B as compared with group C. The present study indicated that the inhibition of lipid substrate oxidation may be responsible for the cardiotoxicity induced by bupivacaine and ropivacaine. The cardiotoxicity induced by ropivacaine is far more less than bupivacaine.

Adenosine Diphosphate↗
PubMed2003

Influence of drugs and nutrients on transporter gene expression levels in Caco-2 and LS180 intestinal epithelial cell lines.

PURPOSE: The aim of this study was to investigate the influences of various drugs and nutrients on the expression levels of intestinal drug transporters PEPT1, MDR1, MRP2 and MRP3, and drug-metabolizing enzyme CYP3A4. METHODS: Quantitative reverse transcriptase polymerase chain reaction was used to quantitate transporter and CYP3A4 mRNAs. Western blotting was used to determine protein levels of P-gp. Transport studies of P-gp were performed using cultured Caco-2 cell monolayers. RESULTS: The expression of MDR1 mRNA was increased by all-trans retinoic acid and in glucose-depleted medium, whereas little change of MRP2 and MRP3 mRNA was observed in Caco-2 cells. Substrates and inducers of P-gp or CYP3A4 tended to produce parallel changes in the expression of MDR1 and CYP3A4 mRNA in LS180 cells, whereas in Caco-2 cells no such coordinate response was observed, possibly due to the absence of the expression of steroid xenobiotic receptor (SXR) in this cell line. CONCLUSION: Several drugs and nutrients were found to affect transporter gene expression level in two human intestinal epithelial cell lines. Since SXR is involved in some expression-regulatory processes, and Caco-2 cells lack SXR, LS180 cells as well as Caco-2 cells should be used for the study of the regulation of intestinal transporters.

ATP Binding Cassette Transporter, Subfamily B, Mem↗