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1.
Nat Commun ; 14(1): 7369, 2023 Nov 14.
Article in English | MEDLINE | ID: mdl-37963911

ABSTRACT

Current techniques for visualizing and quantifying cellular forces have limitations in live cell imaging, throughput, and multi-scale analysis, which impede progress in cell force research and its practical applications. We developed a photonic crystal cellular force microscopy (PCCFM) to image vertical cell forces over a wide field of view (1.3 mm ⨯ 1.0 mm, a 10 ⨯ objective image) at high speed (about 20 frames per second) without references. The photonic crystal hydrogel substrate (PCS) converts micro-nano deformations into perceivable color changes, enabling in situ visualization and quantification of tiny vertical cell forces with high throughput. It enabled long-term, cross-scale monitoring from subcellular focal adhesions to tissue-level cell sheets and aggregates.


Subject(s)
Focal Adhesions , Photons , Microscopy, Atomic Force/methods
2.
Front Microbiol ; 13: 985308, 2022.
Article in English | MEDLINE | ID: mdl-36071965

ABSTRACT

Constipation is a common and typically multifactorial childhood complaint, and the clinical management of childhood functional constipation (FC) is challenging. A randomized, single-blind, placebo-controlled, multi-center clinical trial was conducted in 92 children (47 from Beijing, China and 45 from Shanghai, China) aged 4-12 with FC according to Rome III criteria. Children were assigned to receive a probiotic chewable tablet (5 × 109 CFU/day, n = 47), consisting of Lactobacillus acidophilus DDS-1® and Bifidobacterium animalis subsp. lactis UABla-12™ or placebo (n = 45), twice daily for 4 weeks, followed by a week follow-up period. Results suggested that the probiotic group showed a faster and more pronounced normalization of stool frequency over the intervention period (3.15 vs. 1.83) when compared to placebo group (2.51 vs. 1.87). Meanwhile, the percentage of subjects with hard defecation decreased from 43 to 14% in the probiotic group, while the percentage of subjects with normal defecation increased from 56 to 80% in the probiotic group, further confirming the normalization of stools habits. This randomized controlled trial demonstrated the potential of a probiotic chewable tablet containing L. acidophilus DDS-1® and B. Lactis UABla-12™ as a daily probiotic dosage form for children with FC.

3.
Technol Health Care ; 30(6): 1489-1502, 2022.
Article in English | MEDLINE | ID: mdl-35599513

ABSTRACT

BACKGROUND: The injury of the knee joint is found to be directly related to the fatigue caused by excessive exercise. Many previous studies used wearable devices to measure the angle of knee joint during activities, but did not pay enough attention to the load of knee joint related to the fatigue degree of it. OBJECTIVE: A wearable embedded system was designed to sense the motion state and load of knee joint and uses the sensoring data to estimate and predict the fatigue degree of knee joint during exercise in real time, so as to prevent it from being injured. METHODS: An economical wearable system is designed to measure the parameters of the knee joint during exercises. Then the warning message and recommended healthy lasting time are able to be sent to users to avoid excessive exercise. 24 healthy volunteers aged 20-25 years were involved in the experiments. Two famous evaluation scales for knee joint from Department of Orthopedics (Lysholm score and IKDC score) were adopted to evaluate the protective effect. RESULTS: After 14 days of the first stage testing, all the participants with wearable devices reported healthy knee joint state to verify the effectiveness of the system. For the second stage, the testing group equipped with wearable warning devices did not receive obvious change in the two scales. However, Lysholm score of control group dropped by at least 7.4 and IKDC score dropped by at least 11.1 which were significantly reduced. CONCLUSION: Only using human perception to prevent knee joint fatigue had a risk of failure while the designed wearable system could protect the knee successfully from injuries during exercises, such as running, badminton, table tennis and basketball. Moreover, female gender and a high BMI value may be two factors that increase the risk of knee injuries during sports.


Subject(s)
Knee Injuries , Sports , Wearable Electronic Devices , Female , Humans , Knee Joint , Fatigue
4.
Molecules ; 27(3)2022 Jan 20.
Article in English | MEDLINE | ID: mdl-35163930

ABSTRACT

A number of studies have confirmed the relationship between constipation and gut microbiota. Additionally, many human and animal experiments have identified probiotics as effectors for the relief of constipation symptoms. In this study, probiotic compounds, including Lactobacillus acidophilus LA11-Onlly, Lacticaseibacillus rhamnosus LR22, Limosilactobacillus reuteri LE16, Lactiplantibacillus plantarum LP-Onlly, and Bifidobacterium animalis subsp. lactis BI516, were administered to mice with loperamide-induced constipation, and the impacts of these strains on constipation-related indicators and gut microbiota were evaluated. The effects of probiotic compounds on constipation relief were associated with various aspects, including gastrointestinal transit rate, number and weight of stools, serum and intestinal gastrointestinal regulatory hormones, and serum cytokines. Some of the probiotic compounds, including Limosilactobacillus reuteri, Lactiplantibacillus plantarum, and Lacticaseibacillus rhamnosus, were found to colonize the intestinal tract. Furthermore, higher dosages promoted the colonization of specific strains. This study yields a new perspective for the clinical use of probiotics to improve constipation symptoms by combining strains with different mechanisms for the alleviation of constipation.


Subject(s)
Constipation/drug therapy , Gastrointestinal Microbiome , Gastrointestinal Tract/drug effects , Probiotics/pharmacology , Animals , Constipation/microbiology , Cytokines/metabolism , Feces/microbiology , Gastrointestinal Tract/microbiology , Lactobacillus acidophilus/chemistry , Lacticaseibacillus rhamnosus/chemistry , Male , Mice , Mice, Inbred BALB C
5.
Analyst ; 145(22): 7186-7190, 2020 Nov 09.
Article in English | MEDLINE | ID: mdl-33026362

ABSTRACT

A highly compressible and all-solid-state polydimethylsiloxane (PDMS) sponge-based flexible capacitance sensor modified with polypyrrole (PPy) was designed as the signal readout for the sensitive immunoassay of prostate-specific antigen (PSA). This system mainly consisted of a compressible capacitance sensor, immunoreaction protocol and gas delivery channel. The capacitance sensor was connected to a single microplate by a syringe, whereas the immunoreaction was carried out in the microplate. The conjugated catalase with the detection antibody via biotin-streptavidin interaction could trigger gas generation to cause a pressure change, thus resulting in the increase in the capacitance of the PPy-PDMS sponge observed with an LCR-6100 digital bridge capacitance meter. By coupling with the capacitance sensor, the capacitance change could be monitored in real time to achieve portable detection of PSA. Under the optimal conditions, the compressible supercapacitor PPy-PDMS sponge showed great electrochemical performance and remained stable under compressive strains. The capacitance increased with increasing target PSA concentration within a dynamic working range of 0.1-50 ng mL-1 at a detection limit of 57 pg mL-1. Moreover, acceptable reproducibility, precision and high specificity were obtained from PSA analysis, and were in good accordance with the commercial PSA ELISA kit.


Subject(s)
Polymers , Pyrroles , Dimethylpolysiloxanes , Humans , Immunoassay , Male , Point-of-Care Systems , Prostate-Specific Antigen , Reproducibility of Results
6.
Anal Chem ; 92(3): 2809-2814, 2020 02 04.
Article in English | MEDLINE | ID: mdl-31939295

ABSTRACT

A self-powered temperature sensor based on Seebeck effect transduction was designed for photothermal-thermoelectric coupled immunoassay of α-fetoprotein (AFP). In this system, glucose oxidase (GOx)-conjugated detection antibody was first captured onto the microplate by target-induced sandwich-type immunoreaction. Thereafter, the as-generated hydrogen peroxide via the GOx-glucose system oxidized 3,3',5,5'-tetrametylbenzidine (TMB) into photothermal product oxidized TMB (ox-TMB). Under near-infrared (NIR) laser irradiation, the temperature change of ox-TMB was read out in an electrical signal by the flexible thermoelectric module in a 3D-printed integrated detection device. Under optimal conditions, the photothermal-thermoelectric coupled immunoassay exhibited a limit of detection of 0.39 ng mL-1 AFP over a dynamic linear range from 0.5 to 60 ng mL-1. Impressively, such a strategy presented herein offers tremendous potentials for applying many other high-efficiency thermoelectric materials in ultrasensitive biosensors.


Subject(s)
Biosensing Techniques , Electrochemical Techniques , Immunoassay , Temperature , alpha-Fetoproteins/analysis , Biosensing Techniques/instrumentation , Electrochemical Techniques/instrumentation , Immunoassay/instrumentation , Photochemical Processes
7.
ACS Appl Bio Mater ; 3(12): 9156-9163, 2020 Dec 21.
Article in English | MEDLINE | ID: mdl-35019593

ABSTRACT

An effective signal amplification strategy based on temperature-amplification synergistic pressure was designed for the sensitive detection of carcinoembryonic antigen (CEA) by using a noncontact point-of-care testing (POCT) aptasensor with a flexible pressure sensor based on a poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)-modified sponge (PEDOT:PSS-sponge). In the biological recognition system, target analyte triggered the release of platinum nanoparticle-labeled complementary DNA (Pt-cDNA) from CEA aptamer-conjugated magnetic beads. On the basis of the unique characteristics of platinum nanoparticles (e.g., catalytic ability for H2O2 decomposition, peroxidase-like catalytic activity, and photothermal characteristics), the platinum nanoparticles (PtNPs) could not only catalyze hydrogen peroxide (H2O2) to produce a large amount of oxygen (O2) but could also assist the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to a photothermal agent ox-TMB with the increasing temperature. Under 808 nm near-infrared (NIR) laser irradiation, an increase in the pressure and temperature occurred simultaneously in the closed detection cell. Meanwhile, the increasing temperature could be helpful for further increasing the pressure. The flexible pressure sensor was compressed in a closed system to cause a decrease in contact resistance, thereby establishing a correlation between the concentration and the resistance-readable analysis. Under optimum conditions, the dynamic detection range of this detection strategy for target CEA was between 0.2 and 80 ng mL-1, and the limit of detection (LOD) was 0.15 ng mL-1. Overall, the signal amplification strategy of temperature coordination provides possibilities for the future development of sensitive and portable POCT protocols.

8.
JAMA Netw Open ; 2(5): e193348, 2019 05 03.
Article in English | MEDLINE | ID: mdl-31050781

ABSTRACT

Importance: Thyrotoxic periodic paralysis (TPP) is a potentially lethal complication of hyperthyroidism. However, only 1 specific susceptibility locus for TPP has been identified. Additional genetic determinants should be detected so that a prediction model can be constructed. Objective: To investigate the genetic architecture of TPP and distinguish TPP from Graves disease cohorts. Design, Setting, and Participants: This population-based case-control study used a 2-stage genome-wide association study to investigate the risk loci of TPP and weighted genetic risk score to construct a TPP prediction model with data from a Chinese Han population recruited in hospitals in China from March 2003 to December 2015. The analysis was conducted from November 2014 to August 2016. Main Outcomes and Measures: Loci specifically associated with TPP risk and those shared with Graves disease and prediction model of joint effects of TPP-specific loci. Results: A total of 537 patients with TPP (mean [SD] age, 35 [11] years; 458 male) 1519 patients with Graves disease and no history of TPP (mean [SD] age, 38 [13] years; 366 male), and 3249 healthy participants (mean [SD] age, 46 [10] years; 1648 male) were recruited from the Han population by hospitals throughout China. Two new TPP-specific susceptibility loci were identified: DCHS2 on 4q31.3 (rs1352714: odds ratio [OR], 1.58; 95% CI, 1.35-1.85; P = 1.24 × 10-8) and C11orf67 on 11q14.1 (rs2186564: OR, 1.50; 95% CI, 1.29-1.74; P = 2.80 × 10-7). One previously reported specific locus was confirmed on 17q24.3 near KCNJ2 (rs312729: OR, 2.08; 95% CI, 1.83-2.38; P = 8.02 × 10-29). Meanwhile, 2 risk loci (MHC and Xq21.1) were shared by Graves disease and TPP. After 2 years of treatment, the ratio of persistent thyrotropin receptor antibody positivity was higher in patients with TPP than in patients with Graves disease and no history of TPP (OR, 3.82; 95% CI, 2.04-7.16; P = 7.05 × 10-6). The prediction model using a weighted genetic risk score and 11 candidate TPP-specific single-nucleotide polymorphisms had an area under the curve of 0.80. Conclusions and Relevance: These findings provide evidence that TPP is a novel molecular subtype of Graves disease. The newly identified loci, along with other previously reported loci, demonstrate the growing complexity of the heritable contribution to TPP pathogenesis. A complete genetic architecture will be helpful to understand the pathophysiology of TPP, and a useful prediction model could prevent the onset of TPP.


Subject(s)
Graves Disease/genetics , Thyroid Crisis/genetics , Adult , Asian People/genetics , Case-Control Studies , China , Cross-Sectional Studies , Female , Genome-Wide Association Study , Humans , Male , Middle Aged , Paralysis/genetics , Polymorphism, Single Nucleotide
9.
J Mater Chem B ; 7(6): 908-914, 2019 02 14.
Article in English | MEDLINE | ID: mdl-32255096

ABSTRACT

Enhanced efficiency for generating molecular ions is essential for high-throughput and sensitive detection using mass spectrometry in clinical diagnostics and biomarker discovery. In this study, we developed a novel strategy to promote laser desorption and ionization by using photonic crystals as substrates. The WO3-TiO2 inverse opal photonic crystal, with a coupling stop band and laser wavelength, significantly enhanced the efficiency of laser desorption and ionization owing to the slow light effect and the porous structure of the inverse opal, which increased the interaction between the laser and WO3-TiO2. Furthermore, stress biomarkers were conveniently measured under atmospheric pressure by using WO3-TiO2 inverse opal as an enhanced substrate to evaluate the impact of chronic unpredictable mild stress. The universal and highly sensitive substrate has promised for application in the highly sensitive detection and quantification of biomarkers.


Subject(s)
Biomarkers/analysis , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Animals , Atmospheric Pressure , Biomarkers/blood , Depressive Disorder/diagnosis , Disease Models, Animal , Light , Male , Mice , Mice, Inbred C57BL , Oxides/chemistry , Porosity , Serotonin/blood , Stress, Physiological , Stress, Psychological , Titanium/chemistry , Tungsten/chemistry
10.
Langmuir ; 34(44): 13219-13224, 2018 11 06.
Article in English | MEDLINE | ID: mdl-30352513

ABSTRACT

Patterning colloidal photonic crystals have broad important applications in optical devices, functional coatings, full color displays, and colorimetric sensors. In this paper, a clickable colloidal photonic crystal using vinyl-modified sub-micrometer silica particles as building blocks was proposed to pattern photonic crystals. By click chemistry, different chemical groups were simply grafted to the clickable photonic crystals film and obtained wettability-encoded structure color patterns. The clickable photonic crystals provide a simple, controllable, and rapid path to pattern photonic crystals.

11.
ACS Appl Mater Interfaces ; 10(40): 34611-34617, 2018 Oct 10.
Article in English | MEDLINE | ID: mdl-30211539

ABSTRACT

As a prospective ophthalmic drug delivery device, contact lenses attract a lot of attention because of the improved drug residence time and bioavailability. Herein, we proposed and fabricated a molecular imprinted structural color contact lens for sustained timolol release which could self-report the release process by color change. The specific recognition of target timolol by molecular imprinted sites can not only increase the loading amount and the residence time of the drug but also endow the structure color of lens remarkable blue shift with the accumulative release of timolol. The fascinating contact lens can be further used for controlling release of a large number of ophthalmic drugs and has high potential to be a new generation of functional contact lenses.


Subject(s)
Contact Lenses, Hydrophilic , Drug Delivery Systems/methods , Light , Timolol , Colorimetry/methods , Humans , Timolol/chemistry , Timolol/pharmacokinetics
12.
ACS Appl Mater Interfaces ; 10(35): 29378-29384, 2018 Sep 05.
Article in English | MEDLINE | ID: mdl-30094987

ABSTRACT

High mechanical strength, highly visible, and admirable grafting molecular ability is the key challenge for colloidal photonic crystal (CPC) barcode beads in multiplex analysis fields. To achieve this goal, we proposed self-adhesion particles, polydopamine-coated SiO2 nanoparticles (PDA@SiO2), to construct CPC barcode beads by droplet-based microfluidic approach. Because of the adhesion, broad absorption of light, and "active" functional groups of PDA, the beads are endowed with high robustness, visibility, and excellent biomolecule immobilization. Ultrasonic treatment and compression experiments demonstrated that PDA@SiO2 CPC barcode beads have a high mechanical strength. Color analysis illustrated that PDA@SiO2 CPC beads exhibited a high visibility in color. The verification of fluorescent-tagged biomolecule conjugation together with the antigen detection stated that PDA@SiO2 CPC beads are capable of immobilizing biomolecule by covalent binding. With a sandwich format, the beads were applied to analyze the tumor makers including alpha fetal protein, carcinoembryonic antigen, and prostate specific antigen from practical clinical serum. The proposed suspension arrays using PDA@SiO2 CPC beads as a barcode showed acceptable accuracy and detection reproducibility.


Subject(s)
Biological Assay/methods , Blood Chemical Analysis/methods , Microfluidics , Carcinoembryonic Antigen/analysis , Carcinoembryonic Antigen/blood , Crystallization , Nanoparticles/chemistry , Prostate-Specific Antigen/analysis , Prostate-Specific Antigen/blood , Reproducibility of Results , Silicon Dioxide/chemistry , alpha-Fetoproteins/analysis
13.
Clin Biochem ; 53: 77-80, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29382470

ABSTRACT

BACKGROUND: Modern serum protein electrophoresis (SPE) resolves serum proteins in 6 major fractions, splitting beta (B) into beta1 (B1) and beta2 (B2). Beta-migrating monoclonal immunoglobulins (B-MC) commonly integrate into normal-looking peak shape(s) but may increase the fraction value, forming the basis for reflex testing. The objectives of this study were (1) to ascertain the value of beta fraction(s) reporting, and (2) to compare the diagnostic performance between different beta-flagging approaches, particularly ↑B versus ↑B1 and/or ↑B2. METHODS: We retrospectively studied 22,900 consecutive SPEs, and identified 3974 paired SPE and immunofixation electrophoresis (IFE) results obtained from the Sebia Capillarys™ 2 and Hydrasys™ electrophoresis systems respectively. ↑B, ↑B1 and ↑B2 were defined as fraction concentrations >11, 6 and 5 g/L respectively, and their respective diagnostic metrics calculated using IFE as the reference standard. RESULTS: 32 beta-gamma bridges were B-MC negative and thus excluded. Of 3942 cases, 142, 18, 285 and 300 had ↑B, ↑B1, ↑B2 and ↑B1 and/or ↑B2 respectively, while their corresponding sensitivities for B-MC were 0.38, 0.09, 0.45 and 0.54 respectively. Comparing ↑B and ↑B1 and/or ↑B2, ↑B had significantly lower sensitivity but higher specificity (0.98 Vs 0.95) and positive predictive value (0.47 Vs 0.31). All 4 beta fraction increases had odds ratios ranged from 14 to 118. CONCLUSION: Beta increases were associated with increased odds for B-MC, hence providing value and justification for their reporting and reflex testing. ↑B1 and/or ↑B2 detected more B-MC than ↑B, supporting separate reporting of B1 and B2.


Subject(s)
Antibodies, Monoclonal/blood , Blood Protein Electrophoresis , Female , Humans , Male , Retrospective Studies
14.
Nanoscale ; 10(8): 3673-3679, 2018 Feb 22.
Article in English | MEDLINE | ID: mdl-29327029

ABSTRACT

Here we propose a new method for constructing highly color fast non-iridescent structural color materials by assembling self-adhesive poly-dopamine coated SiO2 nanoparticles (PDA@SiO2) for amorphous colloidal arrays through a "spraying" process. Simply by alkaline vapor treatment, the adhesive forces and fastness of the amorphous colloidal arrays were significantly improved. This was demonstrated by lap shear tests of tape tearing and cohesive failure as well as a series of fastness tests like sandpaper abrasion, finger wiping and ultrasonic cleaning. Besides, the strengthening fastness reaction could occur on different substrates, including glass, metals, polymers and paper, regardless of their chemical and physical properties. Moreover, the structural color of the PDA@SiO2 arrays was bright due to the broadband absorption of PDA, and was tunable according to the size, PDA content and arrangement of the PDA@SiO2 arrays.

15.
Alzheimers Dement (Amst) ; 7: 56-60, 2017.
Article in English | MEDLINE | ID: mdl-28275700

ABSTRACT

INTRODUCTION: White matter hyperintensities (WMH) presumed to reflect cerebral small vessel disease and increased peripheral inflammatory markers are found commonly in Alzheimer's disease (AD), but their interrelationships remain unclear. METHODS: Inflammatory markers were assayed in 54 elderly participants (n = 16 with AD). Periventricular WMH were delineated from T1, T2/proton density, and fluid-attenuated magnetic resonance imaging using semiautomated fuzzy lesion extraction and coregistered with maps of fractional anisotropy (FA), a measure of microstructural integrity assessed using diffusion tensor imaging. RESULTS: Mean FA within periventricular WMH was associated with an inflammatory factor consisting of interleukin (IL)-1ß, tumor necrosis factor, IL-10, IL-21, and IL-23 in patients with AD (ρ = -0.703, P = .002) but not in healthy elderly (ρ = 0.217, P = .190). Inflammation was associated with greater FA in deep WMH in healthy elderly (ρ = 0.425, P = .008) but not in patients with AD (ρ = 0.174, P = .520). DISCUSSION: Peripheral inflammatory markers may be differentially related to microstructural characteristics within the white matter affected by cerebral small vessel disease in elders with and without AD.

16.
J Agric Food Chem ; 64(16): 3206-14, 2016 Apr 27.
Article in English | MEDLINE | ID: mdl-27054263

ABSTRACT

A novel water-soluble polysaccharide-protein complex (PRW1) isolated from the sclerotia of an edible mushroom Polyporus rhinocerus which was purified by membrane ultrafiltration could significantly activate murine macrophages RAW264.7 in vitro. PRW1 had a molecular weight of less than 50 kDa and was found to be a highly branched heteropolysaccharide-protein complex composed of 45.7 ± 0.97% polysaccharide and 44.2 ± 0.41% protein. Based on the results of total acid hydrolysis, methylation analysis, and Fourier transform infrared spectroscopy, the carbohydrate moiety of PRW1 was found to be a ß-d-mannoglucan with its backbone containing →1)-d-Glcp-(4→, →1)-d-Glcp-(6→, and →1)-d-Manp-(2→ residues (molar ratio of 5:4:6) and having terminal d-Glcp as side chain (degree of branching of 0.62). In vitro studies showed that PRW1 significantly induced NO production and enhanced the release of a variety of cytokines including G-CSF, GM-CSF, IL-6, IL12p40/70, MCP-1, MCP-5, MIP-1-α, MIP-2, RANTES, sTNFRI, and TNF-α. Mechanistically, PRW1 treatment triggered ERK phosphorylation to activate macrophages within 15 min and significantly increased the expression level of inducible NOS after 6 h. In summary, this study indicates that PRW1 derived from the sclerotia of P. rhinocerus is a potential immunomodulatory agent for cancer immunotherapy.


Subject(s)
Adjuvants, Immunologic/pharmacology , Fungal Proteins/pharmacology , Macrophages/drug effects , Polyporus/chemistry , Polysaccharides/pharmacology , Animals , Blotting, Western , Cell Line , Chromatography, Gel , Chromatography, High Pressure Liquid , Electrophoresis, Polyacrylamide Gel , Fungal Proteins/chemistry , Macrophages/immunology , Mice , Polysaccharides/chemistry , Spectroscopy, Fourier Transform Infrared
17.
Clin Biochem ; 48(10-11): 674-8, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25828046

ABSTRACT

OBJECTIVES: Hypo-gammaglobulinemia (hypoGG) in serum protein electrophoresis (SPE) reflects, variably, reduced serum immunoglobulin (Ig) concentrations, which may be caused by hematological neoplasms, among other causes. HypoGG in the absence of a discernible M-spike (MC) has been the basis of reflexive testing e.g., by immunofixation electrophoresis (IFE). However, the utility of this practice has not been fully evaluated. Thus, we aimed to (1) determine the predictive power of hypoGG for reduced Ig levels, (2) compare the IFE positive rates and sensitivity between hypoGG and non-hypoGG patients, and (3) examine the M-protein isotype distributions. METHODS: We retrospectively analyzed 3974 matched SPE and IFE results at the Sunnybrook Health Sciences Centre from January 2010 to June 2013. SPE and IFE were performed on the Sebia Capillarys™ 2 and Hydrasys™ systems respectively. RESULTS: 2723/3974 (68.5%) patients were SPE negative, 246/2723 (9%) had hypoGG and 192 (7.1%) were IFE positive. HypoGG predicted 93.1% cases with at least one Ig reduction. Among SPE-negative patients, the IFE positive rate and sensitivity in hypoGG were 12.2% and 15.6% respectively, compared to 6.4% and 77.1% in normo-GG. Proportion of non-IgG isotypes in both groups were comparable but fewer MC were detected in hypoGG. CONCLUSIONS: Both the 7% false negative rate of SPE and the poor sensitivity (16%) of reflex testing based on hypoGG should be taken into consideration when devising a screening strategy based on SPE.


Subject(s)
Agammaglobulinemia/blood , Agammaglobulinemia/diagnosis , Blood Protein Electrophoresis/standards , Hemoglobins/analysis , Blood Protein Electrophoresis/methods , Cohort Studies , Female , Humans , Immunoglobulin G/blood , Male , Retrospective Studies
18.
Hum Mol Genet ; 23(20): 5505-17, 2014 Oct 15.
Article in English | MEDLINE | ID: mdl-24852370

ABSTRACT

Thyroid-stimulating hormone (TSH) is a sensitive indicator of thyroid function. High and low TSH levels reflect hypothyroidism and hyperthyroidism, respectively. Even within the normal range, small differences in TSH levels, on the order of 0.5-1.0 mU/l, are associated with significant differences in blood pressure, BMI, dyslipidemia, risk of atrial fibrillation and atherosclerosis. Most of the variance in TSH levels is thought to be genetically influenced. We conducted a genome-wide association study of TSH levels in 1346 Chinese Han individuals. In the replication study, we genotyped four candidate SNPs with the top association signals in an independent isolated Chinese She cohort (n = 3235). We identified a novel serum TSH susceptibility locus within XKR4 at 8q12.1 (rs2622590, Pcombined = 2.21 × 10(-10)), and we confirmed two previously reported TSH susceptibility loci near FOXE1 at 9q22.33 and near CAPZB at 1p36.13, respectively. The rs2622590_T allele at XKR4 and the rs925489_C allele near FOXE1 were correlated with low TSH levels and were found to be nominally associated to patients with papillary thyroid carcinoma (PTC) (OR = 1.41, P= 0.014 for rs2622590_T, and OR = 1.61, P= 0.030 for rs925489_C). The rs2622590 and rs925489 genotypes were also correlated with the expression levels of FOXE1 and XKR4, respectively, in PTC tissues (P = 2.41 × 10(-4) and P= 0.02). Our findings suggest that the SNPs in XKR4 and near FOXE1 are involved in the regulation of TSH levels.


Subject(s)
Carcinoma/genetics , Forkhead Transcription Factors/genetics , Hypothyroidism/genetics , Membrane Transport Proteins/genetics , Thyroid Neoplasms/genetics , Thyrotropin/blood , Apoptosis Regulatory Proteins , Asian People/genetics , CapZ Actin Capping Protein/genetics , Carcinoma, Papillary , China , Chromosomes, Human, Pair 8/genetics , Chromosomes, Human, Pair 9/genetics , Gene Expression Profiling , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Membrane Proteins , Polymorphism, Single Nucleotide , Thyroid Cancer, Papillary , Thyrotropin/genetics
19.
JAMA ; 310(9): 948-59, 2013 Sep 04.
Article in English | MEDLINE | ID: mdl-24002281

ABSTRACT

IMPORTANCE: Noncommunicable chronic diseases have become the leading causes of mortality and disease burden worldwide. OBJECTIVE: To investigate the prevalence of diabetes and glycemic control in the Chinese adult population. DESIGN, SETTING, AND PARTICIPANTS: Using a complex, multistage, probability sampling design, we conducted a cross-sectional survey in a nationally representative sample of 98,658 Chinese adults in 2010. MAIN OUTCOMES AND MEASURES: Plasma glucose and hemoglobin A1c levels were measured after at least a 10-hour overnight fast among all study participants, and a 2-hour oral glucose tolerance test was conducted among participants without a self-reported history of diagnosed diabetes. Diabetes and prediabetes were defined according to the 2010 American Diabetes Association criteria; whereas, a hemoglobin A1c level of <7.0% was considered adequate glycemic control. RESULTS: The overall prevalence of diabetes was estimated to be 11.6% (95% CI, 11.3%-11.8%) in the Chinese adult population. The prevalence among men was 12.1% (95% CI, 11.7%-12.5%) and among women was 11.0% (95% CI, 10.7%-11.4%). The prevalence of previously diagnosed diabetes was estimated to be 3.5% (95% CI, 3.4%-3.6%) in the Chinese population: 3.6% (95% CI, 3.4%-3.8%) in men and 3.4% (95% CI, 3.2%-3.5%) in women. The prevalence of undiagnosed diabetes was 8.1% (95% CI, 7.9%-8.3%) in the Chinese population: 8.5% (95% CI, 8.2%-8.8%) in men and 7.7% (95% CI, 7.4%-8.0%) in women. In addition, the prevalence of prediabetes was estimated to be 50.1% (95% CI, 49.7%-50.6%) in Chinese adults: 52.1% (95% CI, 51.5%-52.7%) in men and 48.1% (95% CI, 47.6%-48.7%) in women. The prevalence of diabetes was higher in older age groups, in urban residents, and in persons living in economically developed regions. Among patients with diabetes, only 25.8% (95% CI, 24.9%-26.8%) received treatment for diabetes, and only 39.7% (95% CI, 37.6%-41.8%) of those treated had adequate glycemic control. CONCLUSIONS AND RELEVANCE: The estimated prevalence of diabetes among a representative sample of Chinese adults was 11.6% and the prevalence of prediabetes was 50.1%. Projections based on sample weighting suggest this may represent up to 113.9 million Chinese adults with diabetes and 493.4 million with prediabetes. These findings indicate the importance of diabetes as a public health problem in China.


Subject(s)
Blood Glucose/analysis , Diabetes Mellitus/epidemiology , Diabetes Mellitus/therapy , Adolescent , Adult , Age Factors , Aged , China/epidemiology , Cross-Sectional Studies , Data Collection , Diabetes Mellitus/blood , Diabetes Mellitus/diagnosis , Female , Glucose Tolerance Test , Glycated Hemoglobin/analysis , Humans , Male , Middle Aged , Prediabetic State/epidemiology , Prevalence , Rural Population , Urban Population , Young Adult
20.
Hum Mol Genet ; 22(16): 3347-62, 2013 Aug 15.
Article in English | MEDLINE | ID: mdl-23612905

ABSTRACT

Graves' disease (GD), characterized by autoantibodies targeting antigens specifically expressed in thyroid tissues causing hyperthyroidism, is triggered by a combination of genetic and environmental factors. However, only a few loci for GD risk were confirmed in the various ethnic groups, and additional genetic determinants have to be detected. In this study, we carried out a three-stage study in 9529 patients with GD and 9984 controls to identify new risk loci for GD and found genome-wide significant associations in the overall populations for five novel susceptibility loci: the GPR174-ITM2A at Xq21.1, C1QTNF6-RAC2 at 22q12.3-13.1, SLAMF6 at 1q23.2, ABO at 9q34.2 and an intergenic region harboring two non-coding RNAs at 14q32.2 and one previous indefinite locus, TG at 8q24.22 (Pcombined < 5 × 10(-8)). The genotypes of corresponding variants at 14q32.2 and 8q24.22 were correlated with the expression levels of C14orf64 and a TG transcript skipping exon 46, respectively. This study increased the number of GD loci with compelling evidence and indicated that non-coding RNAs might be potentially involved in the pathogenesis of GD.


Subject(s)
Genetic Predisposition to Disease , Graves Disease/genetics , RNA, Untranslated/genetics , Tumor Necrosis Factors/genetics , ABO Blood-Group System/genetics , Adult , Antigens, CD/genetics , Base Sequence , Case-Control Studies , Collagen , DNA, Intergenic , Female , Genetic Loci , Genome-Wide Association Study , Genotype , Humans , Male , Membrane Proteins/genetics , Middle Aged , Molecular Sequence Data , Polymorphism, Single Nucleotide , Receptors, Cell Surface/genetics , Receptors, G-Protein-Coupled/genetics , Signaling Lymphocytic Activation Molecule Family , Signaling Lymphocytic Activation Molecule Family Member 1
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