33 results on '"K. Qian"'
Search Results
2. [Evaluation of bioceramic putty repairmen iRoot and mineral trioxide aggregate in mature permanent teeth pulpotomy]
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K, Qian, J, Pan, W H, Zhu, X Y, Zhao, C, Liu, and W, Yong
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论著 ,Drug Combinations ,Treatment Outcome ,stomatognathic system ,Silicates ,Pulpotomy ,Humans ,Oxides ,Calcium Compounds ,Aluminum Compounds - Abstract
OBJECTIVE: To evaluate the clinical characteristics and effectiveness of pulpotomy in mature permanent teeth with bioceramic putty repairmen iRoot and mineral trioxide aggregate (MTA). METHODS: Pulpotomy was performed on mature permanent premolars and molars with carious exposures at the Department of General Dentistry of Peking University School and Hospital of Stomatology, from November 2017 to September 2019. The patients were randomly divided into 2 groups, Group iRoot (n=22) and Group MTA (n=21). In Group iRoot, bioceramic putty repairmen iRoot was used as pulp capping agent, while in Group MTA, mineral trioxide aggregate was used as pulp capping agent. All the patients had signed informed consent forms. The clinical efficacy was evaluated by clinical examinations (temperature and electrical activity test) and imaging examinations 3, 6, and 12 months after surgery. Blinding was used for the patients and evaluators, but due to the obvious differences in the properties of the two pulp capping agents, the blinding method was not used for the treatment provider (the attending physician). RESULTS: There was no significant difference in gender, average age, dentition and tooth position distribution between the two groups (P>0.05). In the study, 7 cases were lost to follow-up 12 months after operation (4 cases in Group iRoot, and 3 cases in Group MTA). One case in each of the two groups had transient sensitivity at the end of the 3-month follow-up, and the pulp vitality was normal at the end of the 6-month follow-up. One case in Group iRoot showed sensitivity at the end of the 12-month follow-up. The success rates of the two groups at the end of 12-month follow-up were 100%, and the cure rates were 94.4% (Group iRoot) and 100% (Group MTA), respectively, and the difference was not statistically significant (P>0.05). No cases in Group iRoot had obvious crown discoloration, while 3 cases in Group MTA had. CONCLUSION: The clinical characteristics and effectiveness of pulpotomy in mature permanent teeth with bioceramic putty repairmen iRoot were similar with MTA. Bioceramic putty repairmen iRoot is an acceptable material when used in pulpotomy of mature permanent teeth. Because it is not easy to cause tooth discoloration after treatment and is convenient to operate, bioceramic putty repairmen iRoot has a better clinical application prospect.
- Published
- 2022
3. Clinical and in vitro evaluation of new anti‐redness cosmetic products in subjects with winter xerosis and sensitive skin
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X. Wang, D Targett, K Qian, Anthony Vincent Rawlings, Stephanie J Nisbet, Michael A. Thompson, Pallav A. Bulsara, C B Lin, and David J. Moore
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anti‐redness ,Niacinamide ,Aging ,Administration, Topical ,Pharmaceutical Science ,Cosmetics ,Palmitic Acids ,Dermatology ,Filaggrin Proteins ,In Vitro Techniques ,Pharmacology ,medicine.disease_cause ,030226 pharmacology & pharmacy ,Pantothenic Acid ,Sensitive skin ,030207 dermatology & venereal diseases ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Colloid and Surface Chemistry ,safety testing ,Drug Discovery ,medicine ,Humans ,skin barrier ,Involucrin ,Sensitization ,Skin ,Palmitoylethanolamide ,business.industry ,keratinocyte differentiation ,skin physiology ,Original Articles ,Amides ,medicine.anatomical_structure ,Tolerability ,chemistry ,Ethanolamines ,Chemistry (miscellaneous) ,sensitive skin ,Original Article ,Seasons ,Irritation ,business ,Filaggrin ,Panthenol ,medicine.drug - Abstract
Objective To demonstrate the in vitro activities of panthenol, palmitoylethanolamide (PEA), and niacinamide (NAM) and determine the biophysical properties, clinical safety, tolerability together with efficacy of two developmental anti‐redness (AR) formulations containing these ingredients, in alleviating facial redness associated with winter xerosis in healthy volunteers with sensitive skin. Methods The anti‐inflammatory and skin protective properties of panthenol, PEA and NAM were evaluated in vitro. The physical properties of the AR formulations were analysed using measurement of water vapour transport rate (WVTR) and infrared spectroscopy. Clinical studies were performed between the months of December and April (2014–2015) with efficacy assessed during the winter. Facial redness, irritation, sensitization potential, photo‐irritation, and photo‐sensitization were evaluated. Self‐assessed adverse reactions were reported in diaries of use. Results Panthenol and PEA reduced prostaglandin E2, interleukin‐6, and thymic stromal lymphopoietin levels in vitro, while NAM induced nicotinamide adenine dinucleotide (NAD) levels and the keratinocyte differentiation markers: filaggrin (2‐fold increase, P, This article demonstrates the in vitro activities of panthenol, palmitoylethanolamide (PEA), and niacinamide (NAM) and determines the biophysical properties, clinical safety, tolerability together with efficacy of two developmental anti‐redness formulations containing these ingredients, in alleviating facial redness associated with winter xerosis in healthy volunteers with sensitive skin.
- Published
- 2019
4. [Prevalence and risk factors of
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Z H, Hu, H H, Chen, K, Qian, C Q, Ning, G H, Peng, Y F, Yu, X F, Zhou, Y H, Chu, D, Xu, J X, Chen, L G, Tian, and H, Li
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Acquired Immunodeficiency Syndrome ,China ,Feces ,Cross-Sectional Studies ,AIDS-Related Opportunistic Infections ,Risk Factors ,Prevalence ,Humans ,Blastocystis hominis ,HIV Infections ,Blastocystis Infections ,Cities - Abstract
To investigate the prevalence and risk factors ofA cross-sectional questionnaire survey was conducted among AIDS patients in Nanchang City during the period between May and September, 2016.A survey was conducted in Nanchang City from May to September 2016. A total of 505 AIDS patients were investigated, and the prevalence ofThe prevalence of
- Published
- 2020
5. KLF5 promotes proliferation in gastric cancer via regulating p21 and CDK4
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P, Chen, X-K, Qian, Y-F, Zhang, X-G, Sun, X-J, Shi, and Y-S, Gao
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Cyclin-Dependent Kinase Inhibitor p21 ,Male ,Stomach Neoplasms ,Kruppel-Like Transcription Factors ,Cyclin-Dependent Kinase 4 ,Humans ,Female ,Cell Cycle Checkpoints ,Middle Aged ,Cells, Cultured ,Cell Proliferation - Abstract
This study aims to investigate the expression characteristics of Krüppel-like factor 5 (KLF5) in gastric cancer (GC) and its potential correlation to pathological indexes in GC patients. Molecular mechanisms underlying the regulatory effect of KLF5 on GC progression are explored.KLF5 expressions in GC tissues were analyzed through GEPIA dataset and those collected in our hospital. By analyzing the clinical data of GC patients, the correlation between KLF5 level and pathological characteristics of GC was determined. The regulatory effects of KLF5 on proliferative ability and cell cycle progression of SGC7901 and MGC803 cells were assessed by Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) assay, and flow cytometry. The regulation of KLF5 on expression levels of p21 and CDK4 in GC cells was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot.KLF5 was markedly upregulated in GC tissues. KLF5 level was positively correlated to TNM staging, tumor size, and metastasis of GC. Meanwhile, high level of KLF5 predicted poor prognosis in GC patients. The knockdown of KLF5 in SGC7901 and MGC803 cells attenuated proliferative ability and arrested cell cycle in G0/G1 phase. Both mRNA and the protein levels of p21 were upregulated, and CDK4 levels were downregulated in SGC7901 and MGC803 cells transfected with si-KLF5.KLF5 is upregulated in GC and closely linked to pathological characteristics of GC patients. High level of KLF5 indicates poor prognosis of GC. It is believed that KLF5 may be a potential therapeutic target for GC.
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- 2020
6. Differential developmental courses of implicit and explicit biases for different other-race classes
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Paul C. Quinn, Kang Lee, Genyue Fu, Gail D. Heyman, and Miao K. Qian
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Adult ,Male ,Adolescent ,Poison control ,Article ,Developmental psychology ,Race (biology) ,Young Adult ,Child Development ,Racism ,5. Gender equality ,Asian People ,Social cognition ,Developmental and Educational Psychology ,Ethnicity ,Humans ,0501 psychology and cognitive sciences ,10. No inequality ,Life-span and Life-course Studies ,Child ,Socioeconomic status ,Demography ,05 social sciences ,Age Factors ,Ingroups and outgroups ,Child development ,Socioeconomic Factors ,Child, Preschool ,Female ,Implicit attitude ,Psychology ,050104 developmental & child psychology ,Social status - Abstract
We investigated the developmental courses of both implicit and explicit racial biases in relation to the perceived social status of outgroups. We did so by assessing these biases among Chinese participants (N = 200, age range from 4- to 19-year-olds) toward 2 different other-race groups that differ in terms of perceived social status (i.e., Whites and Blacks). At the youngest age, children showed both implicit anti-White and anti-Black bias at similar levels. However, these biases had different patterns of age-related change: implicit anti-Black bias remained strong and stable over time, whereas implicit anti-White bias declined after age 10. For explicit bias, children showed a decline in anti-Black and anti-White bias. Implicit and explicit biases were uncorrelated at all ages. The observed age-related changes demonstrate that it is possible for patterns of biases toward different races to diverge with age, and that perceived social status may contribute to the differential developmental patterns. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
- Published
- 2019
7. [The technique and efficacy of complete resection of mesogastrium above the pancreas by the right approach in laparoscopic assisted distal gastrectomy for radical gastrectomy]
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J, Min, K, Qian, X X, Wu, Z W, Wang, and W, Zhang
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Gastrectomy ,Stomach Neoplasms ,Humans ,Lymph Node Excision ,Laparoscopy ,Mesentery ,Retrospective Studies - Published
- 2018
8. Eliciting promises from children reduces cheating
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Genyue Fu, Gail D. Heyman, Jianyan Lin, Kang Lee, and Miao K. Qian
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Behavior Control ,Male ,Motivation ,Deception ,ComputingMilieux_THECOMPUTINGPROFESSION ,media_common.quotation_subject ,Cheating ,ComputingMilieux_PERSONALCOMPUTING ,Experimental and Cognitive Psychology ,Neuropsychological Tests ,Temptation ,Developmental psychology ,Compliance (psychology) ,Executive Function ,Social order ,Moral development ,Child, Preschool ,Developmental and Educational Psychology ,Humans ,Female ,Child ,Function (engineering) ,Psychology ,Social psychology ,media_common - Abstract
Widespread cheating can undermine rules that are necessary for maintaining social order. Preventing cheating can be a challenge, especially with regard to children, who as a result of their limited executive function skills may have particular difficulty with resisting temptation to cheat. We examined one approach designed to help children resist this temptation: eliciting a verbal commitment to not cheat. We tested 4- to 7-year-olds (total N = 330) and found that starting at 5 years of age, a verbal commitment to not cheat led to a substantial reduction in cheating. The results suggest that verbal commitments can be used to help children overcome temptations and comply with rules.
- Published
- 2015
9. Constitutively Active MDA5 Proteins Are Inhibited by Paramyxovirus V Proteins
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Curt M. Horvath, Roli Mandhana, and Lily K Qian
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0301 basic medicine ,Interferon-Induced Helicase, IFIH1 ,Immunology ,Biology ,law.invention ,03 medical and health sciences ,Viral Proteins ,Interferon ,law ,Virology ,Gene expression ,medicine ,Humans ,MDA5 ,Research Reports ,Cell Biology ,Vesiculovirus ,Cell biology ,Cytosol ,030104 developmental biology ,HEK293 Cells ,Viral replication ,Nucleic acid ,Suppressor ,Homeostasis ,medicine.drug ,Signal Transduction - Abstract
Excessive interferon (IFN) production and signaling can lead to immunological and developmental defects giving rise to autoimmune diseases referred to collectively as "type I interferonopathies." A subset of these diseases is caused by monogenic mutations affecting proteins involved in nucleic acid sensing, homeostasis, and metabolism. Interferonopathic mutations in the cytosolic antiviral sensor MDA5 render it constitutively hyperactive, resulting in chronic IFN production and IFN-stimulated gene expression. Few therapeutic options are available for patients with interferonopathic diseases, but a large number of IFN evasion and antagonism strategies have evolved in viral pathogens that can counteract IFN production and signaling to enhance virus replication. To test the hypothesis that these natural IFN suppressors could be used to subdue the activity of interferonopathic signaling proteins, hyperactive MDA5 variants were assessed for susceptibility to a family of viral MDA5 inhibitors. In this study, Paramyxovirus V proteins were tested for their ability to counteract constitutively active MDA5 proteins. Results indicate that the V proteins are able to bind to and disrupt the signaling activity of these MDA5 proteins, irrespective of their specific mutations, reducing IFN production and IFN-stimulated gene expression to effectively suppress the hyperactive antiviral response.
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- 2018
10. Using the Fluorescence Red Edge Effect to Assess the Long-Term Stability of Lyophilized Protein Formulations
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Marcus T. Cicerone, Madhusudan Tyagi, Ken K. Qian, and Pawel Grobelny
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Glycerol ,Sucrose ,Fluorophore ,Chemistry, Pharmaceutical ,Analytical chemistry ,Pharmaceutical Science ,Molecular Dynamics Simulation ,Protein degradation ,Neutron scattering ,Mole fraction ,Fluorescence ,Protein Structure, Secondary ,Rhodamine 6G ,chemistry.chemical_compound ,Drug Stability ,Drug Discovery ,Humans ,Scattering, Radiation ,Fluorescent Dyes ,Neutrons ,Human Growth Hormone ,Chemistry ,Relaxation (NMR) ,Temperature ,Proteins ,Trehalose ,Freeze Drying ,Spectrometry, Fluorescence ,Molecular Medicine ,Glass ,Debye–Waller factor - Abstract
Nanosecond relaxation processes in sugar matrices are causally linked through diffusional processes to protein stability in lyophilized formulations. Long-term protein degradation rates track mean-squared displacement (⟨u(2)⟩) of hydrogen atoms in sugar glasses, a parameter describing dynamics on a time scale of picoseconds to nanoseconds. However, measurements of ⟨u(2)⟩ are usually performed by neutron scattering, which is not conducive to rapid formulation screening in early development. Here, we present a benchtop technique to derive a ⟨u(2)⟩ surrogate based on the fluorescence red edge effect. Glycerol, lyophilized trehalose, and lyophilized sucrose were used as model systems. Samples containing 10(-6) mole fraction of rhodamine 6G, a fluorophore, were excited at either 532 nm (main peak) or 566 nm (red edge), and the ⟨u(2)⟩ surrogate was determined based the corresponding Stokes shifts. Results showed reasonable agreement between ⟨u(2)⟩ from neutron scattering and the surrogate from fluorescence, although deviations were observed at very low temperatures. We discuss the sources of the deviations and suggest technique improvements to ameliorate these. We expect that this method will be a valuable tool to evaluate lyophilized sugar matrices with respect to their ability to protect proteins from diffusion-limited degradation processes during long-term storage. Additionally, the method may have broader applications in amorphous pharmaceutical solids.
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- 2015
11. MiR-873 regulates ERα transcriptional activity and tamoxifen resistance via targeting CDK3 in breast cancer cells
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J Cui, Y Yang, H Li, Y Leng, K Qian, Q Huang, C Zhang, Z Lu, J Chen, T Sun, R Wu, Y Sun, H Song, X Wei, P Jing, and X Yang
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Transcriptional Activation ,Cancer Research ,medicine.medical_specialty ,Antineoplastic Agents, Hormonal ,Mice, Nude ,Estrogen receptor ,Breast Neoplasms ,Biology ,Gene Expression Regulation, Enzymologic ,Breast cancer ,Internal medicine ,microRNA ,Genetics ,medicine ,Animals ,Humans ,Phosphorylation ,skin and connective tissue diseases ,Molecular Biology ,Cell Proliferation ,Binding Sites ,Base Sequence ,Cell growth ,Kinase ,Cyclin-Dependent Kinase 3 ,Estrogen Receptor alpha ,Cyclin-dependent kinase 3 ,medicine.disease ,Xenograft Model Antitumor Assays ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,Tamoxifen ,Endocrinology ,Drug Resistance, Neoplasm ,MCF-7 Cells ,Cancer research ,Female ,RNA Interference ,Protein Processing, Post-Translational ,Estrogen receptor alpha ,medicine.drug - Abstract
miRNAs (microRNAs) are frequently and aberrantly expressed in many cancers. MiR-873 has been revealed to be downregulated in colorectal cancer and glioblastoma. However, its function remains unclear. Here we report that miR-873 is downregulated in breast tumor compared with normal tissue. Enforced expression of miR-873 decreases the transcriptional activity of ER (estrogen receptor)-α but not ERβ through the modulation of ERα phosphorylation in ER-positive breast cancer cells. We also found that miR-873 inhibits breast cancer cell proliferation and tumor growth in nude mice. Reporter gene assays revealed cyclin-dependent kinase 3 (CDK3) as a direct target of miR-873. CDK3 was shown to be overexpressed in breast cancer and phosphorylate ERα at Ser104/116 and Ser118. Furthermore, we found that Mir-873 inhibits ER activity and cell growth via targeting CDK3. Interestingly, miR-873 was observed to be downregulated in tamoxifen-resistant MCF-7/TamR cells, while CDK3 is overexpressed in these cells. More importantly, re-expression of miR-873 reversed tamoxifen resistance in MCF-7/TamR cells. Our data demonstrate that miR-873 is a novel tumor suppressor in ER-positive breast cancer and a potential therapeutic approach for treatment of tamoxifen-resistant breast cancer.
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- 2014
12. TGF-β1 promotes human hepatic carcinoma HepG2 cells invasion by upregulating autophagy
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C-L, Ma, S, Qiao, Y-C, Li, X-F, Wang, R-J, Sun, X, Zhang, R-K, Qian, and S-D, Song
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Transforming Growth Factor beta1 ,Carcinoma, Hepatocellular ,Dose-Response Relationship, Drug ,Adenine ,Liver Neoplasms ,Autophagy ,Humans ,Beclin-1 ,Neoplasm Invasiveness ,Hep G2 Cells ,Microtubule-Associated Proteins ,Up-Regulation - Abstract
To study the role of TGF-β1 in autophagy and invasion ability of human hepatic carcinoma HepG2 cells.Cultured HepG2 cells were treated with different concentrations of TGF-β1 for 24 h. The protein expression levels of autophagy relative marker LC3 and Beclin1 were detected by Western blot. The effect of TGF-β1 on invasion ability of HepG2 cells was detected with transwell method.The results demonstrated that TGF-β1 was able to activate autophagy of HepG2 cells in a dose-dependent manner. Autophagy inhibitor 3-methyladenine (3-MA) could reverse TGF-β1 induced autophagy process. Also, TGF-β1 significantly promotes the invasion ability of HepG2 cells; however, this process could effectively reverse by autophagy inhibitor 3-MA.TGF-β1 enhances HepG2 cells invasion by upregulating autophagy.
- Published
- 2017
13. [Retrospective comparison of screening criteria for active surveillance for papillary thyroid microcarcinoma]
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K, Qian, T Q, Sun, K, Guo, X K, Zheng, D S, Li, W W, Wei, Y, Wu, Q H, Ji, and Z Y, Wang
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Male ,China ,Consensus ,Kaplan-Meier Estimate ,Prognosis ,Carcinoma, Papillary ,Disease-Free Survival ,Lymphatic Metastasis ,Population Surveillance ,Humans ,Female ,Lymph Nodes ,Thyroid Neoplasms ,Neoplasm Recurrence, Local ,Neck ,Retrospective Studies - Published
- 2017
14. Perceptual individuation training (but not mere exposure) reduces implicit racial bias in preschool children
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Paul C. Quinn, Genyue Fu, Gail D. Heyman, Miao K. Qian, Olivier Pascalis, Kang Lee, Hangzhou Normal University, University of Delaware [Newark], University of California [San Diego] (UC San Diego), University of California, Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire de Psychologie et NeuroCognition (LPNC ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and University of Toronto
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Male ,Face perception ,media_common.quotation_subject ,education ,Child Behavior ,[SHS.PSY]Humanities and Social Sciences/Psychology ,050109 social psychology ,PsycINFO ,050105 experimental psychology ,Article ,Developmental psychology ,Individuation ,Racism ,Perception ,Developmental and Educational Psychology ,Humans ,Learning ,0501 psychology and cognitive sciences ,Life-span and Life-course Studies ,Child ,Demography ,media_common ,Social perception ,05 social sciences ,Social Perception ,Child, Preschool ,Racial bias ,Causal link ,Female ,Implicit attitude ,Psychology ,Facial Recognition - Abstract
International audience; Two studies with preschool-age children examined the effectiveness of perceptual individuation training at reducing racial bias (Study 1, N = 32; Study 2, N = 56). We found that training preschool-age children to individuate other-race faces resulted in a reduction in implicit racial bias while mere exposure to other-race faces produced no such effect. We also showed that neither individuation training nor mere exposure reduced explicit racial bias. Theoretically, our findings provide strong evidence for a causal link between individual-level face processing and implicit racial bias, and are consistent with the newly proposed perceptual-social linkage hypothesis. Practically, our findings suggest that offering children experiences that allow them to increase their expertise in processing individual other-race faces will help reduce their implicit racial bias. (PsycINFO Database Record
- Published
- 2017
15. A Long-Term Effect of Perceptual Individuation Training on Reducing Implicit Racial Bias in Preschool Children
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Paul C. Quinn, Kang Lee, Gail D. Heyman, Genyue Fu, Miao K. Qian, Olivier Pascalis, Hangzhou Normal University, University of Toronto, Department of Psychological and Brain Sciences, University of Delaware [Newark], University of California [San Diego] (UC San Diego), University of California, Zhejiang Normal University, Laboratoire de Psychologie et NeuroCognition (LPNC ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Department of Psychology
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Male ,China ,media_common.quotation_subject ,Personal Satisfaction ,Training (civil) ,Racism ,050105 experimental psychology ,White People ,Article ,Education ,Developmental psychology ,Individuation ,Discrimination, Psychological ,Asian People ,Intervention (counseling) ,Phenomenon ,Perception ,Developmental and Educational Psychology ,Humans ,0501 psychology and cognitive sciences ,10. No inequality ,media_common ,05 social sciences ,Contrast (statistics) ,Black or African American ,Social Perception ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,[SCCO.PSYC]Cognitive science/Psychology ,Racial bias ,Female ,Psychology ,Facial Recognition ,050104 developmental & child psychology ,Cognitive psychology - Abstract
International audience; This study tracked the long-term effect of perceptual individuation training on reducing 5-year-old Chinese children's (N = 95, M age = 5.64 years) implicit pro-Asian/anti-Black racial bias. Initial training to individuate other-race Black faces, followed by supplementary training occurring 1 week later, resulted in a long-term reduction of pro-Asian/anti-Black bias (70 days). In contrast, training Chinese children to recognize White or Asian faces had no effect on pro-Asian/anti-Black bias. Theoretically, the finding that individuation training can have a long-term effect on reducing implicit racial bias in preschoolers suggests that a developmentally early causal linkage between perceptual and social processing of faces is not a transitory phenomenon. Practically , the data point to an effective intervention method for reducing implicit racism in young children.
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- 2017
16. [miR-34b-3p regulates the angiogenesis of senescent endothelial cell]
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J W, Wang, P, Chen, X K, Qian, Y H, Li, J, Cui, X N, Zhu, Y, Wang, S M, Wang, and J S, Wang
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MicroRNAs ,Human Umbilical Vein Endothelial Cells ,Humans ,Neovascularization, Physiologic ,Real-Time Polymerase Chain Reaction ,Transfection ,Cells, Cultured ,Cell Proliferation ,Up-Regulation - Abstract
To investigate the effect of miR-34b-3p on the proliferation, migration and tube formation of senescent endothelial cell.Primary human umbilical vein endothelial cells (HUVECs) were cultured in vitro, and population doubling levels (PDLs) were calculated by passage. The young endothelial cell was defined as PDL8. The senescent endothelial cell was defined as PDL44. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was applied to detect the expression of miR-34b-3p in PDL8 and PDL44 HUVECs. miR-34b-3p mimic and inhibitor were transfected into PDL8 and PDL44 HUVECs. Then, cell counting kit-8 (CCK-8), transwell and tube formation assays were used to determine the proliferation, migration and tube formation of HUVECs, respectively.miR-34b-3p was significantly up-regulated approximately 4.3 times in PDL44 HUVECs than that in PDL44 HUVECs (t=-4.528, P0.05). The proliferation, migration, total tube length and branch points of miR-34b-3p in PDL8 HUVECs group were significantly higher approximately 1.2 (0.67/0.57), 1.2 (106/86), 1.4 (10 605/7 735) and 1.3 (41/31) times than that in PDL44 HUVECs group, respectively (t=3.237, 3.564, 5.165, 3.487, P0.05 or P0.01). Overexpression of miR-34b-3p had significantly inhibited proliferation, migration, total tube length and branch points approximately 2.2 (0.67/0.30), 2.3 (106/46), 1.6 (10 605/6 652) and 1.9 (41/22) times in PDL8 HUVECs, respectively (F=145.898, 53.026, 41.997, 36.341, all P0.01). Repression of miR-34b-3p had significantly increased proliferation, migration, total tube length and branch points approximately 1.4 (0.77/0.57), 2.3 (198/86), 1.7 (13 073/7 735) and 2.3 (71/31) times in PDL44 HUVECs, respectively (F=14.815, 42.970, 167.063, 258.340, all P0.01).The high expression of miR-34b-3p in senescent HUVECs could impair the proliferation, migration and tube formation of senescent endothelial cell.
- Published
- 2016
17. Skin compatibility and efficacy of a cosmetic skin care regimen with licochalcone A and 4-t-butylcyclohexanol in patients with rosacea subtype I
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K. Qian, Andrea M. Schoelermann, MJ Babcock, Ronald L. Rizer, C E Arrowitz, and T.M. Weber
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0301 basic medicine ,Adult ,medicine.medical_specialty ,Erythema ,Detergents ,Skin Cream ,TRPV Cation Channels ,Dermatology ,medicine.disease_cause ,Severity of Illness Index ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Chalcones ,Cleanser ,Surveys and Questionnaires ,Severity of illness ,medicine ,Humans ,Telangiectasis ,business.industry ,Anti-Inflammatory Agents, Non-Steroidal ,Middle Aged ,medicine.disease ,Cyclohexanols ,Skin Care ,Regimen ,030104 developmental biology ,Infectious Diseases ,Tolerability ,Rosacea ,Quality of Life ,Drug Therapy, Combination ,Female ,Irritation ,medicine.symptom ,business ,Sunscreening Agents - Abstract
Background Patients with rosacea often show facial sensitivity to cosmetics or skin care products that can influence the severity of symptoms and exacerbate erythema and inflammation. Nevertheless, special skin care is necessary to address cosmetic concerns and reduce the potential side-effects of topical or oral treatment of the disease. Appropriate skin care should comprise gentle cleansing, effective moisturization, soothing actives, UV protection and concealing pigments to help neutralize the appearance of redness. Objective To determine the compatibility and efficacy of a skin care regimen (consisting of a cleanser, a day care with SPF25 and a night care) containing licochalcone A (Lic A), an anti-irritant from the licorice plant Glycyrrhiza inflata, and 4-t-butylcyclohexanol (SymSitive®), a substance which acts as a sensitivity regulator, in female subjects with clinically determined subtype I rosacea. Methods Thirty-two test subjects with mild to moderate rosacea used the skin care regimen daily for 8 weeks. Clinical assessment of erythema, subjective irritation and clinical photography were performed at baseline and after 4 and 8 weeks. Additionally, a quality-of-life questionnaire was filled out by the test subjects at baseline and week 8. The subjects completed a self-assessment questionnaire on product properties after 4 and 8 weeks of product use. Results Clinical assessments and subject response confirmed very good tolerability of the regimen, a statistically significant improvement in clinical grading for erythema and tactile roughness at weeks 4 and 8 and on telangiectasia at week 8 when compared to baseline scores. A statistically significant improvement in facial redness (a*) values, based on the L*a*b* colorimetric system, was determined at week 4 and 8 in comparison to baseline. No difference in corneometric measurement was detected at week 4 and 8 compared to baseline. Conclusion The skin care regimen was found to be highly compatible with the sensitive facial skin of patients with rosacea subtype I and effective in improving signs of rosacea. Therefore, the daily use of skin care products containing LicA and SymSitive® in patients with rosacea improves the overall skin appearance and the quality of life of these patients.
- Published
- 2015
18. Addition of Monovalent Electrolytes to Improve Storage Stability of Freeze-Dried Protein Formulations
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Marcus T. Cicerone, Ming Liu, Hiroshika Goshima, Ken K. Qian, Michael J. Pikal, Madhusudan Tyagi, and Kelly M. Forney-Stevens
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Sucrose ,Chemistry, Pharmaceutical ,Pharmaceutical Science ,Halide ,02 engineering and technology ,Electrolyte ,Protein aggregation ,030226 pharmacology & pharmacy ,03 medical and health sciences ,Freeze-drying ,chemistry.chemical_compound ,Electrolytes ,0302 clinical medicine ,Drug Stability ,medicine ,Animals ,Humans ,Bovine serum albumin ,Molality ,Chromatography ,biology ,Chemistry ,Proteins ,Serum Albumin, Bovine ,021001 nanoscience & nanotechnology ,Human serum albumin ,Freeze Drying ,biology.protein ,Cattle ,0210 nano-technology ,medicine.drug - Abstract
This study investigates the effect of low levels of electrolytes on storage stability in freeze-dried sucrose-based protein formulations. Both bovine serum albumin and recombinant human serum albumin were freeze dried with sucrose and alkali halides (LiCl, NaCl, KCl, RbCl, and CsCl) at selected low levels. All formulations were stored at 50 °C and 65 °C up to 2 months and then assayed for protein aggregation. The data demonstrate that low levels of LiCl and NaCl enhance stability. No obvious correlations with either protein secondary structure or global dynamics (structural relaxation time) were found. However, good correlations were found between stability and both free-volume hole size via positron annihilation lifetime spectroscopy (PALS) and fast dynamics by neutron scattering. Volume changes on mixing and the partial molal volume of salt were also studied in an effort to detect decreases in free volume. These data did not support the hypothesis that reduction in free volume was the primary mechanism for salt-induced stabilization. Finally, a positive effect of postlyophilization annealing on stability was demonstrated. In summary, we find that small amounts of LiCl and NaCl significantly stabilize these proteins, which is a result at variance with conventional formulation wisdom.
- Published
- 2015
19. Stabilization of proteins in solid form
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Michael J. Pikal, Ken K. Qian, and Marcus T. Cicerone
- Subjects
Strongly coupled ,Chemistry ,Chemistry, Pharmaceutical ,Pharmaceutical Science ,Proteins ,Nanotechnology ,Active protein ,Stability (probability) ,Article ,Hydrobromic Acid ,Protein stability ,Biopharmaceutical ,Drug Delivery Systems ,Drug Stability ,Delayed-Action Preparations ,Degradation (geology) ,Humans ,Biological system - Abstract
Immunogenicity of aggregated or otherwise degraded protein delivered from depots or other biopharmaceutical products is an increasing concern, and the ability to deliver stable, active protein is of central importance. We review characterization approaches for solid protein dosage forms with respect to metrics that are intended to be predictive of protein stability against aggregation and other degradation processes. Each of these approaches is ultimately motivated by hypothetical connections between protein stability and the material property being measured. We critically evaluate correlations between these properties and stability outcomes, and use these evaluations to revise the currently standing hypotheses. Based on this we provide simple physical principles that are necessary (and possibly sufficient) for generating solid delivery vehicles with stable protein loads. Essentially, proteins should be strongly coupled (typically through H-bonds) to the bulk regions of a phase-homogeneous matrix with suppressed β relaxation. We also provide a framework for reliable characterization of solid protein forms with respect to stability.
- Published
- 2014
20. [The animal experiments and clinical trial of impeller pump used as left ventricular or biventricular assist device]
- Author
-
K, Qian, P, Zeng, W, Ru, H, Yuan, and M, Zheng
- Subjects
Male ,Clinical Trials as Topic ,Animals ,Humans ,Trilogy of Fallot ,Cattle ,Equipment Failure ,Equipment Design ,Heart-Assist Devices ,Child - Abstract
The authors' impeller pump as a left ventricular or biventricular assist device was evaluated in animal experiments and clinical trial. Three calves survived over 6 weeks in left ventricular assist experiments and neither blood damage nor organ dysfunction of the animals was detected. In clinical trial, the pump supported both the greater and lesser circulation of a 6-year-old child with trilogy of Fallot and low output syndrome after open heart surgery. In 43 hours the pump worked properly. The pump weighing 240 g can perform either in pulsatile or in nonpulsatile mode. In pulsatile pumping, the impeller changes its rotating speed periodically by introducing a square wave form voltage into the motor coil.
- Published
- 2003
21. [The application of neural network to output estimation of an impeller artificial heart]
- Author
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L, Li, P, Zeng, W, Ru, H, Yuan, and K, Qian
- Subjects
Models, Cardiovascular ,Humans ,Heart, Artificial ,Neural Networks, Computer ,Cardiac Output ,In Vitro Techniques ,Algorithms - Abstract
In this paper, several methods of output estimation of artificial heart are introduced briefly, and the authors put forward a method for the application of neural network to the output estimation of an impeller artificial heart. According to the laboratory results, the application of neural network can solve the problem successfully.
- Published
- 2002
22. Infections caused by Flavimonas oryzihabitans
- Author
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K, Qian and S, Wang
- Subjects
Adult ,Male ,Microbial Sensitivity Tests ,Middle Aged ,Anti-Bacterial Agents ,Killer Cells, Natural ,T-Lymphocyte Subsets ,Child, Preschool ,Pseudomonas ,Humans ,Female ,Pseudomonas Infections ,Aged ,Retrospective Studies - Abstract
To assess retrospectively the clinical characteristics and cell immune function of infections caused by Flavimonas oryzihabitans (F. oryzihabitans).We indentified 11 cases of F. oryzihabitans positive cultures from all microbial cultures collected in our hospital from November 1994 to December 1998. Relevant clinical information was collected, including demographic data, underlying disease, and clinical manifestations of the F. oryzihabitans infections. Minimal inhibitory concentrations (MICs) of 15 antimicrobial agents against the 11 F. oryzihabitans isolates were determined. Cell immune function tests were determined by flow cytometry including T lymphocyte subsets (CD3, CD4, CD8 and ratio CD4/CD8) and NK cells (CD16 + 56) from peripheral blood.Six of these patients with infections caused by F. oryzihabitans were male, 5 were female and the mean age was 47.64 years (range, 5 to 69 years). All but 1 patients had severe underlying diseases. 9 (81.8%) of these patients developed infection while hospitalization and 2 (18.2%) before hospitalization (Cases 2 and 5). 8 (72.7%) of these patients manifested primary F. oryzihabitans bacteremia and one each (9.1%) had pleurisy, soft tissue infection and peritonitis. All these isolates were susceptible to amikacin, gentamicin and ciprofloxacin, but resistance to cefazolin, nitrofurantoin, penicillin and piperacillin. CD3, CD4, CD4/CD8 and CD16 + 56 value (mean +/- s) of these patients were significantly lower than normal values (P0.01). The mean time of body temperature fellor = 37 degrees C after antibiotic treatment in these patients was 3.5 days (range, 1 to 6 days). All clinical symptom caused F. oryzihabitans after antibiotic treatment disappeared and all patients recovered.Infections caused by F. oryzihabitans was very few clinically, and relative to underlying diseases and the presence of foreign material. Immune function abnormality was among mostly factor for the F. oryzihabitans infections.
- Published
- 2002
23. [Counteracting effect of Chinese herbs-compounds on 'blood stasis' induced by bed rest]
- Author
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B Z, Wang, H Z, Shi, J Y, Gao, Q C, Fan, Z M, Xu, and J K, Qian
- Subjects
Adult ,Head-Down Tilt ,Adolescent ,Blood Circulation ,Aerospace Medicine ,Humans ,Blood Pressure ,Urine ,Pulse ,Weightlessness Countermeasures ,Bed Rest ,Weightlessness Simulation ,Drugs, Chinese Herbal - Abstract
Objective. To observe the improved effect of syndromes of blood stasis by taking Chinese medicine during bed-rest simulated weightlessness. Method. Ten subjects were randomly divided into two groups: Chinese medicine group and control group. Both of them were exposed to HDBR -6 degrees for a week. The Chinese medicine group took Chinese medicine during the bed rest, and the control group took sugar water. Result. Syndromes of blood stasis of Chinese medicine group had a significant relief. And some physiological parameters, such as blood pressure, pulse graph, and amount of urine, maintained the level of pre-bed rest. While the control group was more severe than the Chinese medicine group in syndromes of blood stasis. Conclusion. Chinese medicine can be a measure in preventing the effect of weightlessness.
- Published
- 2002
24. [Counteracting effect of Chinese herbs on 'insufficiency of spleen qi' induced by simulated weightlessness]
- Author
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H Z, Shi, B Z, Wang, J Y, Gao, J K, Qian, and Q C, Fan
- Subjects
Qi ,Body Weight ,Thymus Gland ,Rats ,Hindlimb Suspension ,Aerospace Medicine ,Animals ,Humans ,Rats, Wistar ,Muscle, Skeletal ,Weightlessness Countermeasures ,Spleen ,Weightlessness Simulation ,Drugs, Chinese Herbal - Abstract
Objective. To observe the counteracting effect of a Chinese herb-compound on "insufficiency of spleen qi" induced by simulated weightlessness. Methods. Animal and human experiment were carried out to the Chinese herb-compound (Dangshen, Baizhu, Fuling etc). Result. This compound protected the tail suspended rats from atrophy of spleen, thymus, soleus and gastrocnemius muscles, prevented excessive decrease of body weight effectively; at the same time it relieved the symptoms of the subjects greatly. Conclusion. It demonstrated that the compound decreased the "insufficiency of spleen qi" of both animals and human subjects.
- Published
- 2002
25. [Clinical implications of HCV quasispecies heterogeneity in patients with hepatitis C]
- Author
-
X, Tang, K, Qian, and J Y, Lau
- Subjects
Adult ,Male ,Adolescent ,Humans ,Female ,Hepacivirus ,Middle Aged ,Hepatitis C ,Polymorphism, Single-Stranded Conformational ,Aged - Abstract
To determine the heterogeneity of viral quasispecies and its clinical significance in patients with hepatitis C.Quasispecies in the sera from 76 patients infected with hepatitis C virus were detected using single stranded conformational polymorphism (SSCP) analysis of the HCV E2 hypervariable region 1 (HVR1).HVR1 was amplified in 72 (94.7%) of the 76 patients. The average number of SSCP bands was 5.8, with a range from 2 to 11. The numbers of quasispecies in acute hepatitis, chronic hepatitis and liver cirrhosis and/or primary hepatocellular carcinoma were 3.1 +/- 1.2, 6.0 +/- 2.3 and 8.4 +/- 4.1, respectively. There was a statistically significant difference among them (P0.01). Patients with infection acquired by blood transfusion and i.v. drug use had greater number of quasispecies than those acquired by other transmission pathway (sporadic) (P0.05). Patients with genotype 1 a and 1 b infection had increased quasispecies compared with those infected with HCV type 2 and 3(P0.05). Increased quasispecies heterogeneity was significantly correlated with serum HCV RNA levels (P0.01).SSCP is a simple, rapid and reliable method for the analysis of HCV viral quasispecies heterogeneity. Quasispecies heterogeneity plays an important role in HCV persistent infection and in the progress of hepatitis C. The duration of HCV infection, HCV genotype and HCV viremia are important determinants for the evolution of HCV quasispecies heterogeneity.
- Published
- 2001
26. [Determination of chloramphenicol in chloramphenicol and dexamethasone sodium phosphate ear drops by first derivative spectrometry]
- Author
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H, Ma, G, Tan, Z, Zhang, J, Yang, K, Qian, J, Ding, and B, Xie
- Subjects
Drug Combinations ,Pharmaceutical Solutions ,Chloramphenicol ,Humans ,Spectrophotometry, Ultraviolet ,Ear Diseases ,Dexamethasone ,Anti-Bacterial Agents - Abstract
Determination of chloramphenicol in the ear drops by first derivative spectrometry was studied. The detecting wavelength was 303.0 nm. The linear range was 0-65.2 micrograms.ml-1 (r = 0.9999). The average recovery was 99.84%, RSD = 0.37% (n = 8). The method is simple and accurate.
- Published
- 2001
27. Dialectic classification of syndrome diagnosis in traditional Chinese medicine used as new criterion for evaluating prognosis of patients with cervical cancer
- Author
-
Yang Jx, Peng Yw, Le Zhang, S Yu, and Z K Qian
- Subjects
medicine.medical_specialty ,Pathology ,medicine.medical_treatment ,Uterine Cervical Neoplasms ,Disease ,Traditional Chinese medicine ,Tongue ,Management of Technology and Innovation ,Internal medicine ,Statistical significance ,Humans ,Medicine ,Medicine, Chinese Traditional ,Survival rate ,Cervical cancer ,business.industry ,Prognosis ,medicine.disease ,Survival Rate ,Radiation therapy ,Yin Deficiency ,Yang Deficiency ,medicine.anatomical_structure ,Medicine public health ,Carcinoma, Squamous Cell ,Female ,business - Abstract
254 patients with cervical cancer were treated by radiotherapy from Jan 1979 to Dec 1984. All the patients were followed up at least for more than 3 years, of them 180 for over 5 years. According to various symptoms, picture of the tongue and pulse condition, the disease was classified into 4 types, namely: 1) deficiency of liver-yin and kidney-yin, 2) deficiency of splenic qi, 3) internal retention of damp-heat, and 4) stagnation of qi and blood or stagnation of liver qi. The survival rate of the various types was quite different. The patients of type 4 had the worst prognosis. The prognosis of patients with type 1 was significantly better than that of patients with type 4. The difference was of statistical significance (P less than 0.01).
- Published
- 1991
28. Detection of GB virus-C/hepatitis G virus RNA in serum by reverse transcription polymerase chain reaction
- Author
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B, Bhardwaj, K, Qian, J, Detmer, M, Mizokami, J A, Kolberg, M S, Urdea, G, Schlauder, J M, Linnen, J P, Kim, G L, Davis, and J Y, Lau
- Subjects
Adult ,Male ,Base Sequence ,Hepatitis, Viral, Human ,Flaviviridae ,Molecular Sequence Data ,Hepacivirus ,Middle Aged ,Polymerase Chain Reaction ,Humans ,RNA, Viral ,Female ,Serologic Tests ,Promoter Regions, Genetic ,Aged - Abstract
Three PCR methods based on the GB virus-C/hepatitis G virus (GBV-C/HGV) 5'UTR and NS3 genomic region were used for the detection of GBV-C/HGV RNA in serum of 62 patients with chronic hepatitis C virus (HCV) infection. Ten of 62 (16%) patients were found to have GBV-C/HGV RNA, which was confirmed by sequence analysis of the 5'UTR PCR amplicon. All methods appear to be specific, but methods based on the 5'UTR appear to be more sensitive.
- Published
- 1997
29. [Simultaneous determination of eight kinds of conjunct bile acids in human bile by R-HPLC]
- Author
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Z, Dai, G, Tan, K, Qian, and X, Chen
- Subjects
Bile Acids and Salts ,Cholelithiasis ,Bile ,Humans ,Chromatography, High Pressure Liquid - Abstract
A method for the simultaneous determination of eight kinds of conjunct bile acids in human bile was developed by HPLC. They were separated on a YWG-C18 (3 microns) column at 30 degrees C, with methanol/water (65/35, V/V, pH3.0) as mobile phase, and detection wavelength at UV 210 nm. The linear ranges were 50-1,000 microns.ml-1, the recoveries were 91.2%-108.6%. The biles of 30 cases with cholelithiasis cholecystolithiasis and 20 cases without gallstone were detected by HPLC. The results showed that the constitution of bile acids was different between patients with cholelithiasis cholecystolithiasis and patients without gallstone.
- Published
- 1997
30. Clinical implications of viral quasispecies heterogeneity in chronic hepatitis C
- Author
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R P, González-Peralta, K, Qian, J Y, She, G L, Davis, T, Ohno, M, Mizokami, and J Y, Lau
- Subjects
Adult ,Male ,Reproducibility of Results ,Hepacivirus ,Middle Aged ,Hepatitis C ,Polymerase Chain Reaction ,Genetic Heterogeneity ,Viral Envelope Proteins ,Chronic Disease ,Humans ,RNA, Viral ,Female ,Polymorphism, Single-Stranded Conformational ,Aged - Abstract
To determine the clinical significance of viral quasispecies heterogeneity, 59 patients with chronic hepatitis C were studied using singlestranded conformational polymorphism (SSCP) analysis of the HCV E2 hypervariable region 1 (HVR1); of these, 48 were subsequently treated with interferon-alpha. The SSCP method was validated using clones of known nucleotide sequence. HVR1 was amplified in 54 of 59 (92%) patients. The median number of SSCP bands per sample was 6 (range: 2-12). Increased quasispecies heterogeneity correlated with the estimated duration of HCV infection (P0.05), parenteral-acquired HCV infection (vs. sporadic, P0.05), serum HCV RNA levels (P0.05), and HCV genotype 1 infection (P0.05), but not with age, serum AST, ALT, or Knodell score. Patients who had complete and sustained response to interferon-alpha (n = 11) had lower pre-treatment quasispecies heterogeneity compared to patients who had complete response with relapse (n = 18, P0.05) or no complete response (n = 16, P0.01). However, multivariate analysis revealed that HCV viremia was a stronger predictor of response to interferon-alpha. These findings indicate that the estimated duration of HCV carriage, serum HCV RNA levels, and HCV type 1 are important determinants for the evolution of HCV quasispecies heterogeneity; and that increased HCV quasispecies heterogeneity is another marker associated with a poor subsequent response to interferon-alpha.
- Published
- 1996
31. Medicinal protection with Chinese herb-compound against radiation damage
- Author
-
R J, Zhang, J K, Qian, G H, Yang, B Z, Wang, and X L, Wen
- Subjects
Phenylpropionates ,Radiotherapy ,Incidence ,Leukopenia ,Sitosterols ,Hemostatics ,Mice ,Radiation Injuries, Experimental ,Glucosides ,Neoplasms ,Animals ,Humans ,Asparagine ,Drugs, Chinese Herbal - Abstract
Experiments were carried out on mice and the subjects irradiated for cancer therapy to evaluate the protective efficacy of a Chinese medicinal herb-compound (CMHC). The lethality and the degree of leucopenia caused by radiation in mice medicated with CMHC were significantly less in comparison with control mice (p less than 0.01 and p less than 0.001, respectively). CMHC significantly improved the WBC and the thrombocytes in irradiated workers (p less than 0.01 and p less than 0.001, respectively). The WBC count of 40 patients under radiotherapy while treated with CMHC recovered from 3450 +/- 77/c.mm to 5425 +/- 264/c.mm (p less than 0.001); whereas, in the control group, without any medication, the WBC count dropped significantly (p less than 0.001). Our results revealed the applicabilities of CMHC in protection against radiation damage in spaceflight and in other fields.
- Published
- 1990
32. [Application of the bian zhen lun zhi principle to special environmental medicine]
- Author
-
R J, Zhang, G H, Yang, and J K, Qian
- Subjects
Radioisotopes ,X-Rays ,Humans ,Environmental Exposure ,Medicine, Chinese Traditional ,Microwaves ,Noise - Published
- 1987
33. The function of Shp2 tyrosine phosphatase in the dispersal of acetylcholine receptor clusters
- Author
-
H. Benjamin Peng, Yueping K. Qian, Ariel W.S. Chan, and Raghavan Madhavan
- Subjects
animal structures ,Microinjections ,Xenopus ,Phosphatase ,Green Fluorescent Proteins ,Immunoblotting ,Muscle Fibers, Skeletal ,Neuromuscular Junction ,Protein Tyrosine Phosphatase, Non-Receptor Type 11 ,Protein tyrosine phosphatase ,Biology ,Neuromuscular junction ,lcsh:RC321-571 ,Cell Line ,RNA, Complementary ,Myoblasts ,Cellular and Molecular Neuroscience ,Catalytic Domain ,medicine ,Myocyte ,Animals ,Humans ,Receptors, Cholinergic ,Tyrosine ,Receptors, Immunologic ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Cells, Cultured ,In Situ Hybridization ,Acetylcholine receptor ,Agrin ,Rhodamines ,General Neuroscience ,lcsh:QP351-495 ,Receptor Protein-Tyrosine Kinases ,Bungarotoxins ,Molecular biology ,Antigens, Differentiation ,Cell biology ,lcsh:Neurophysiology and neuropsychology ,medicine.anatomical_structure ,Microscopy, Fluorescence ,Quinolines ,Signal transduction ,Research Article ,Signal Transduction - Abstract
Background A crucial event in the development of the vertebrate neuromuscular junction (NMJ) is the postsynaptic enrichment of muscle acetylcholine (ACh) receptors (AChRs). This process involves two distinct steps: the local clustering of AChRs at synapses, which depends on the activation of the muscle-specific receptor tyrosine kinase MuSK by neural agrin, and the global dispersal of aneural or "pre-patterned" AChR aggregates, which is triggered by ACh or by synaptogenic stimuli. We and others have previously shown that tyrosine phosphatases, such as the SH2 domain-containing phosphatase Shp2, regulate AChR cluster formation in muscle cells, and that tyrosine phosphatases also mediate the dispersal of pre-patterned AChR clusters by synaptogenic stimuli, although the specific phosphatases involved in this latter step remain unknown. Results Using an assay system that allows AChR cluster assembly and disassembly to be studied separately and quantitatively, we describe a previously unrecognized role of the tyrosine phosphatase Shp2 in AChR cluster disassembly. Shp2 was robustly expressed in embryonic Xenopus muscle in vivo and in cultured myotomal muscle cells, and treatment of the muscle cultures with an inhibitor of Shp2 (NSC-87877) blocked the dispersal of pre-patterned AChR clusters by synaptogenic stimuli. In contrast, over-expression in muscle cells of either wild-type or constitutively active Shp2 accelerated cluster dispersal. Significantly, forced expression in muscle of the Shp2-activator SIRPα1 (signal regulatory protein α1) also enhanced the disassembly of AChR clusters, whereas the expression of a truncated SIRPα1 mutant that suppresses Shp2 signaling inhibited cluster disassembly. Conclusion Our results suggest that Shp2 activation by synaptogenic stimuli, through signaling intermediates such as SIRPα1, promotes the dispersal of pre-patterned AChR clusters to facilitate the selective accumulation of AChRs at developing NMJs.
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