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1.  EPO improves the proliferation and inhibits apoptosis of trophoblast and decidual stromal cells through activating STAT-5 and inactivating p38 signal in human early pregnancy 
The erythropoietin (EPO) belongs to the family of angiogenic factors, which is regulated by Hypoxia-inducible factor- 1α (HIF-1α). As known, EPO are expressed in human villi and decidua, but the function is not clear. In this study, we investigated the expression and roles of HIF-1α, EPO and its receptor (EPOR) in the biological functions of trophoblast and decidual stromal cell (DSC) in human early pregnancy. The expression of EPO, EPOR and HIF-1α was evaluated in the villi and deciduas by RT-PCR and immunohistochemistry. Thereafter, we silenced HIF-1α expression in HTR-8/SVneo cell line and decidual stromal cells (DSCs). The effects of EPO on the proliferation and apoptosis of trophoblasts and DSCs, and activation of signal molecules were investigated by BrdU proliferation assay, flow cytometry and western blot, respectively. We have observed that the HIF-1α silence results in the lower expression of EPO in trophoblasts and DSCs. The anti-EPO neutralizing antibody can inactivate the phosphorylation of STAT5 and activate p38 of these cells in a dosage-dependent manner. Furthermore, the expressions of EPO, EPOR and HIF-1α in the villi and decidua from the unexplained miscarriage were significantly lower than that of the normal early pregnancy. This study suggests that HIF-1α may regulate the expression of EPO, which plays a favorable regulatory role in the proliferation and survival of human first-trimester trophoblast cells and DSCs via inactivating p38 and activating STAT5 in an autocrine manner, while the inadequate EPO expression at maternal-fetal interface may lead to pregnancy wastage in humans.
PMCID: PMC3225788  PMID: 22135724
EPO; HIF-1; trophoblast cell; decidual stromal cell; STAT5; p38
2.  Activated Scavenger Receptor A Promotes Glial Internalization of Aβ 
PLoS ONE  2014;9(4):e94197.
Beta-amyloid (Aβ) aggregates have a pivotal role in pathological processing of Alzheimer’s disease (AD). The clearance of Aβ monomer or aggregates is a causal strategy for AD treatment. Microglia and astrocytes are the main macrophages that exert critical neuroprotective roles in the brain. They may effectively clear the toxic accumulation of Aβ at the initial stage of AD, however, their functions are attenuated because of glial overactivation. In this study, we first showed that heptapeptide XD4 activates the class A scavenger receptor (SR-A) on the glia by increasing the binding of Aβ to SR-A, thereby promoting glial phagocytosis of Aβ oligomer in microglia and astrocytes and triggering intracellular mitogen-activated protein kinase (MAPK) signaling cascades. Moreover, XD4 enhances the internalization of Aβ monomers to microglia and astrocytes through macropinocytosis or SR-A-mediated phagocytosis. Furthermore, XD4 significantly inhibits Aβ oligomer-induced cytotoxicity to glial cells and decreases the production of proinflammatory cytokines, such as TNF-α and IL-1β, in vitro and in vivo. Our findings may provide a novel strategy for AD treatment by activating SR-A.
PMCID: PMC3981768  PMID: 24718459
3.  The adhesion of mussel foot protein-3 to TiO2 surfaces: the effect of pH 
Biomacromolecules  2013;14(4):1072-1077.
The underwater adhesion of marine mussels relies on mussel foot proteins (mfps) rich in the catecholic amino acid 3, 4-dihydroxyphenylalanine (Dopa). As a side-chain, Dopa is capable of strong bidentate interactions with a variety of surfaces, including many minerals and metal oxides. Titanium is among the most widely used medical implant material and quickly forms a TiO2 passivation layer under physiological conditions. Understanding the binding mechanism of Dopa to TiO2 surfaces is therefore of considerable theoretical and practical interest. Using a surface forces apparatus, we explored the force-distance profiles and adhesion energies of mussel foot protein 3 (mfp-3) to TiO2 surfaces at three different pHs (pH3, 5.5 and 7.5). At pH3, mfp-3 showed the strongest adhesion force on TiO2, with an adhesion energy of ~ −7.0 mJ/m2. Increasing the pH gives rise to two opposing effects: (1) increased oxidation of Dopa, thus decreasing availability for the Dopa-mediated adhesion, and (2) increased bidentate Dopa-Ti coordination, leading to the further stabilization of the Dopa group and thus an increasing of adhesion force. Both effects were reflected in the resonance-enhanced Raman spectra obtained at the three deposition pHs. The two competing effects give rise to a higher adhesion force of mfp-3 on TiO2 surface at pH 7.5 than at pH 5.5. Our results suggest that Dopa-containing proteins and synthetic polymers have great potential as coating materials for medical implant materials, particularly if redox activity can be controlled.
PMCID: PMC3635841  PMID: 23452271
4.  Anatomical Characteristics of Pulmonary Veins for the Prediction of Postoperative Recurrence after Radiofrequency Catheter Ablation of Atrial Fibrillation 
PLoS ONE  2014;9(4):e93817.
The relationship between focal pulmonary vein potential and atrial fibrillation (AF) has been confirmed. Pulmonary vein (PV) isolation and circumferential pulmonary vein ablation have been the most commonly used procedures of radiofrequency ablation. However, few studies have investigated the relationship between anatomical characteristics of PV and AF recurrences after radiofrequency ablation.
For 267 AF patients treated by radiofrequency catheter ablation, the anatomic structure characteristics of pulmonary veins were assessed by multi-slice spiral computed tomography while the values of left atrial diameter (LAD) were measured with transesophageal ultrasonic cardiogram. After radiofrequency catheter ablation, postoperative recurrence was evaluated during a 10-month term follow-up.
Principal Findings
During follow-up, postoperative recurrence occurred in 44 patients. The mean diameters of LAD, left superior PV, right superior PV, all left PV, and all superior PV were significantly larger in patients with postoperative recurrence (Recurrence vs. Non-recurrence group; 43.9 ± 6.4 mm vs. 40.7 ± 5.6 mm; 18.4 ± 2.1 mm vs. 17.1 ± 3.1 mm; 18.2 ± 2.8 mm vs. 17.2 mm ± 3.9 mm; 16.4 ± 1.5 mm vs. 15.6 ± 2.5 mm; 18.3 ± 2.1 mm vs. 17.1 ± 3.0 mm; respectively; all P < 0.05). Multivariable survival analysis showed that the type and the course of AF, LAD, and the diameters of all superior PV were the independent risk factors for the postoperative recurrence after radiofrequency catheter ablation.
The enlargements of all superior PV and LAD, long course of diseases, and persistent AF were the independent risk factors for the postoperative recurrence after radiofrequency catheter ablation.
PMCID: PMC3976314  PMID: 24705909
5.  Development of asymmetric inhibition underlying direction selectivity in the retina 
Nature  2010;469(7330):402-406.
Establishing precise synaptic connections is crucial to the development of functional neural circuits. The direction-selective circuit in the retina relies upon highly selective wiring of inhibitory inputs from starburst amacrine cells1 (SACs) onto four subtypes of on–off direction-selective ganglion cell (DSGC), each preferring motion in one of four cardinal directions2. It has been reported in rabbit that the SACs on the ‘null’ sides of DSGCs form functional GABA (γ-aminobutyric acid)-mediated synapses, whereas those on the preferred sides do not3. However, it is not known how the asymmetric wiring between SACs and DSGCs is established during development. Here we report that in transgenic mice with cell-type-specific labelling, the synaptic connections from SACs to DSGCs were of equal strength during the first postnatal week, regardless of whether the SAC was located on the preferred or null side of the DSGC. However, by the end of the second postnatal week, the strength of the synapses made from SACs on the null side of a DSGC significantly increased whereas those made from SACs located on the preferred side remained constant. Blocking retinal activity by intraocular injections of muscimol or gabazine during this period did not alter the development of direction selectivity. Hence, the asymmetric inhibition between the SACs and DSGCs is achieved by a developmental program that specifically strengthens the GABA-mediated inputs from SACs located on the null side, in a manner not dependent on neural activity.
PMCID: PMC3974627  PMID: 21131947
6.  The Absence of Longitudinal Data Limits the Accuracy of High-Throughput Clinical Phenotyping for Identifying Type 2 Diabetes Mellitus Subjects 
To evaluate the impact of insufficient longitudinal data on the accuracy of a high-throughput clinical phenotyping (HTCP) algorithm for identifying 1) patients with type 2 diabetes mellitus (T2DM) and 2) patients with no diabetes.
Retrospective study conducted at Mayo Clinic in Rochester, Minnesota. Eligible subjects were Olmsted County residents with ≥1 Mayo Clinic encounter in each of three time periods : 1) 2007, 2) from 1997 through 2006, and 3) before 1997 (N= 54,283). Diabetes relevant electronic medical record (EMR) data about diagnoses, laboratories, and medications were used. We employed the HTCP algorithm to categorize individuals as T2DM cases and non-diabetes controls. Considering the full 11 years (1997–2007) as the gold standard, we compared gold-standard categorizations with those using data for 10 subsequent intervals, ranging from 1998–2007 (10-year data) to 2007 (1-year data). Positive predictive values (PPVs) and false-negative rates (FNRs) were calculated. McNemar tests were used to determine whether categorizations using shorter time periods differed from the gold standard. Statistical significance was defined as P<.05.
We identified 2,770 T2DM cases and 21,005 controls when the algorithm was applied using 11-year data. Using 2007 data alone, PPVs and FNRs respectively were 70% and 25% for case identification and 59% and 67% for control identification. All time frames differed significantly from the gold standard, except for the 10-year period.
The accuracy of the algorithm reduced remarkably as data were limited to shorter observation periods. This impact should be considered carefully when designing/executing HTCP algorithms.
PMCID: PMC3478423  PMID: 22762862
diabetes mellitus; electronic medical record; phenotype; data aggregation; medical informatics; research subject selection
7.  ALOX5 Is Associated with Tuberculosis in a Subset of the Pediatric Population of North China 
Background: Genetic factors are involved in the etiology of Mycobacterium tuberculosis infection. Recently, ALOX5 has been identified as a candidate gene for tuberculosis (TB) susceptibility. We investigated whether an association between ALOX5 and TB exists in a Chinese pediatric population from northern China. Methods: We conducted a case–control study comprising 488 individuals aged 2 months to 17 years by genotyping 18 tag-single-nucleotide polymorphisms (SNPs) from the ALOX5 gene. The tag-SNPs were selected from the international HapMap project. An Illumina BeadXpress Scanner was utilized for genotyping, supported by the high-density BeadArray technology in combination with an allele-specific extension, adapter ligation, and amplification assay. Statistical analyses were performed to determine correlations between genetic variation and disease. Results: Our study is the first to show that ALOX5 is associated with susceptibility to pediatric TB in a subset of children in northern China. The rs2115819 T allele of ALOX5 presents a risk factor for childhood TB disease.
PMCID: PMC3609609  PMID: 23448388
8.  The role of VuMATE1 expression in aluminium-inducible citrate secretion in rice bean (Vigna umbellata) roots 
Journal of Experimental Botany  2013;64(7):1795-1804.
Aluminium (Al)-activated citrate secretion plays an important role in Al resistance in a number of plant species, such as rice bean (Vigna umbellata). This study further characterized the regulation of VuMATE1, an aluminium-activated citrate transporter. Al stress induced VuMATE1 expression, followed by the secretion of citrate. Citrate secretion was specific to Al stress, whereas VuMATE1 expression was not, which could be explained by a combined regulation of VuMATE1 expression and Al-specific activation of VuMATE1 protein. Pre-treatment with a protein translation inhibitor suppressed VuMATE1 expression, indicating that de novo biosynthesis of proteins is required for gene expression. Furthermore, post-treatment with a protein translation inhibitor inhibited citrate secretion, indicating that post-transcriptional regulation of VuMATE1 is critical for citrate secretion. Protein kinase and phosphatase inhibitor studies showed that reversible phosphorylation was important not only for transcriptional regulation of VuMATE1 expression but also for post-translational regulation of VuMATE1 protein activity. These results suggest that citrate secretion is dependent on both transcriptional and post-transcriptional regulation of VuMATE1. Additionally, VuMATE1 promoter–β-glucuronidase fusion lines revealed that VuMATE1 expression was restricted to the root apex and was entirely Al induced, indicating the presence of cis-acting elements regulating root tip-specific and Al-inducible gene expression, which will be an important resource for genetic improvement of plant Al resistance.
PMCID: PMC3638816  PMID: 23408830
aluminium toxicity; cis-acting element; promoter; reversible phosphorylation; signalling transduction; transcription factor.
9.  Identification and Analysis of Differential miRNAs in PK-15 Cells after Foot-and-Mouth Disease Virus Infection 
PLoS ONE  2014;9(3):e90865.
The alterations of MicroRNAs(miRNAs) in host cell after foot-and-mouth disease virus (FMDV) infection is still obscure. To increase our understanding of the pathogenesis of FMDV at the post-transcriptional regulation level, Solexa high-throu MicroRNAs (miRNAs) play an important role both in the post-transcriptional regulation of gene expression and host-virus interactions. Despite investigations of miRNA expression ghput sequencing and bioinformatic tools were used to identify differentially expressed miRNAs and analyze their functions during FMDV infection of PK-15cells. Results indicated that 9,165,674 and 9,230,378 clean reads were obtained, with 172 known and 72 novel miRNAs differently expressed in infected and uninfected groups respectively. Some of differently expressed miRNAs were validated using stem-loop real-time quantitative RT-PCR. The GO annotation and KEGG pathway analysis for target genes revealed that differently expressed miRNAs were involved in immune response and cell death pathways.
PMCID: PMC3968000  PMID: 24675746
10.  Heart Rate and Heart Rate Variability Assessment Identifies Individual Differences in Fear Response Magnitudes to Earthquake, Free Fall, and Air Puff in Mice 
PLoS ONE  2014;9(3):e93270.
Fear behaviors and fear memories in rodents have been traditionally assessed by the amount of freezing upon the presentation of conditioned cues or unconditioned stimuli. However, many experiences, such as encountering earthquakes or accidental fall from tree branches, may produce long-lasting fear memories but are behaviorally difficult to measure using freezing parameters. Here, we have examined changes in heartbeat interval dynamics as physiological readout for assessing fearful reactions as mice were subjected to sudden air puff, free-fall drop inside a small elevator, and a laboratory-version earthquake. We showed that these fearful events rapidly increased heart rate (HR) with simultaneous reduction of heart rate variability (HRV). Cardiac changes can be further analyzed in details by measuring three distinct phases: namely, the rapid rising phase in HR, the maximum plateau phase during which HRV is greatly decreased, and the recovery phase during which HR gradually recovers to baseline values. We showed that durations of the maximum plateau phase and HR recovery speed were quite sensitive to habituation over repeated trials. Moreover, we have developed the fear resistance index based on specific cardiac response features. We demonstrated that the fear resistance index remained largely consistent across distinct fearful events in a given animal, thereby enabling us to compare and rank individual mouse’s fear responsiveness among the group. Therefore, the fear resistance index described here can represent a useful parameter for measuring personality traits or individual differences in stress-susceptibility in both wild-type mice and post-traumatic stress disorder (PTSD) models.
PMCID: PMC3965551  PMID: 24667366
11.  Bismuthoxyiodide Nanoflakes/Titania Nanotubes Arrayed p-n Heterojunction and Its Application for Photoelectrochemical Bioanalysis 
Scientific Reports  2014;4:4426.
We have developed sensitive detection of cancer biomarker vascular endothelial growth factor (VEGF) using the p-n heterojunction comprised of p-type BiOI nanoflakes (NFs) array and n-type TiO2 nanotubes (NTs) array. Due to the unique arrayed structure and the synergy effect of photoelectrochemistry in the formed p-n junction, the synthesized configuration has superior excitation efficiency and thus excellent photoresponsibility. Then, the fabricated p-n heterojunction was integrated with an exquisite bioassay protocol for addressing VEGF using a sandwich immunoassay with glucosedehydrogenase (GDH) as the enzyme tags. Due to the excellent performance of BiOI NFs array/TiO2 NTs array and the ingenious signaling mechanism, the proposed system could achieve the sensitive and specific VEGF detection. This work not only presents a simple BiOI NFs array/TiO2 NTs array p-n heterojunction for general applications in the broad photochemistry areas, but also opens a different horizon for current development of advanced PEC biomolecular detection.
PMCID: PMC3961734  PMID: 24651880
12.  Effects of THAP11 on Erythroid Differentiation and Megakaryocytic Differentiation of K562 Cells 
PLoS ONE  2014;9(3):e91557.
Hematopoiesis is a complex process regulated by sets of transcription factors in a stage-specific and context-dependent manner. THAP11 is a transcription factor involved in cell growth, ES cell pluripotency, and embryogenesis. Here we showed that THAP11 was down-regulated during erythroid differentiation but up-regulated during megakaryocytic differentiation of cord blood CD34+ cells. Overexpression of THAP11 in K562 cells inhibited the erythroid differentiation induced by hemin with decreased numbers of benzidine-positive cells and decreased mRNA levels of α-globin (HBA) and glycophorin A (GPA), and knockdown of THAP11 enhanced the erythroid differentiation. Conversely, THAP11 overexpression accelerated the megakaryocytic differentiation induced by phorbol myristate acetate (PMA) with increased percentage of CD41+ cells, increased numbers of 4N cells, and elevated CD61 mRNA levels, and THAP11 knockdown attenuated the megakaryocytic differentiation. The expression levels of transcription factors such as c-Myc, c-Myb, GATA-2, and Fli1 were changed by THAP11 overexpression. In this way, our results suggested that THAP11 reversibly regulated erythroid and megakaryocytic differentiation.
PMCID: PMC3956667  PMID: 24637716
13.  Genetic Contribution of CISH Promoter Polymorphisms to Susceptibility to Tuberculosis in Chinese Children 
PLoS ONE  2014;9(3):e92020.
Tuberculosis (TB) is the leading cause of death due to an infectious disease worldwide, particularly in developing countries. A series of candidate genes have been suggested to be associated with development of TB disease. Among them, the human Cytokine-inducible Src homology 2(SH2) domain protein (CISH) gene has been very recently reported to be involved in T cell activation and differentiation in response to Mycobacterium tuberculosis infection. Here, we studied the association between CISH promoter polymorphisms and pediatric TB. A case-control study enrolled 352 TB patients and 527 healthy controls, who were of Han Chinese ethnicity and aged from 0.2 to 18 years. CISH gene promoter SNPs rs414171, rs622502 and rs809451 were genotyped in all subjects and transcriptional activity, mRNA level, and plasma cytokine level of subjects with different genotypes were further examined. Carriers with rs414171TT homozygotes and rs809451GC heterozygotes had a 1.78-fold (95% CI,1.16–2.74) and 1.86-fold (95% CI, 1.26–2.74) excess risk of developing TB compared to those with wild-type genotypes. A greater risk of TB disease was observed in population carrying C−809451-T−414171-C−622502 haplotype (OR 3.66, 95% CI:2.12–6.32). The G−809451-A−414171-C−622502-containing CISH promoter drove a 5.43-fold increased reporter expression compared to the C−809451-T−414171-C−622502-containing counterpart in Hela cell lines (P = 0.0009). PBMCs carrying rs414171TT homozygotes and rs809451GC heterozygotes showed a reduced CISH mRNA level compared to cells carrying wild type genotypes. Individuals with the rs414171TT genotype had significantly increased IL-12p40 and IL-10 production. In conclusion, CISH promoter rs414171 and rs809451 polymorphisms may play a vital role in mediating individual susceptibility to tuberculosis.
PMCID: PMC3954833  PMID: 24632804
14.  Dendritic Cells Pulsed with Leukemia Cell-Derived Exosomes More Efficiently Induce Antileukemic Immunities 
PLoS ONE  2014;9(3):e91463.
Dendritic cells (DCs) and tumor cell-derived exosomes have been used to develop antitumor vaccines. However, the biological properties and antileukemic effects of leukemia cell-derived exosomes (LEXs) are not well described. In this study, the biological properties and induction of antileukemic immunity of LEXs were investigated using transmission electron microscopy, western blot analysis, cytotoxicity assays, and animal studies. Similar to other tumor cells, leukemia cells release exosomes. Exosomes derived from K562 leukemia cells (LEXK562) are membrane-bound vesicles with diameters of approximately 50–100 μm and harbor adhesion molecules (e.g., intercellular adhesion molecule-1) and immunologically associated molecules (e.g., heat shock protein 70). In cytotoxicity assays and animal studies, LEXs-pulsed DCs induced an antileukemic cytotoxic T-lymphocyte immune response and antileukemic immunity more effectively than did LEXs and non-pulsed DCs (P<0.05). Therefore, LEXs may harbor antigens and immunological molecules associated with leukemia cells. As such, LEX-based vaccines may be a promising strategy for prolonging disease-free survival in patients with leukemia after chemotherapy or hematopoietic stem cell transplantation.
PMCID: PMC3951359  PMID: 24622345
15.  Combining Human and Rat Sequences in Her-2 DNA Vaccines Blunts Immune Tolerance and Drives Antitumor Immunity 
Cancer research  2010;70(1):119-128.
Immune tolerance to tumor-associated self-antigens poses a major challenge in the ability to mount an effective cancer vaccine response. To overcome immune tolerance to HER-2, we formulated DNA vaccines that express both human HER-2 and heterologous rat Neu sequences in separate plasmids or as single hybrid constructs that encode HER-2/Neu fusion proteins. Candidate vaccines were tested in Her-2 transgenic (Tg) mice of BALB/c (BALB), BALB/c × C57BL/6 F1 (F1), or C57BL/6 (B6) background, which exhibit decreasing immune responsiveness to HER-2. Analysis of various cocktails or hybrid vaccines defined a requirement for particular combination of HER/2/Neu sequences to effectively prime immune effector cells in HER-2 Tg mice. In B6 HER-2 Tg mice, rejection of HER-2–positive tumors protected mice from HER-2–negative tumors, providing evidence of epitope spreading. Our findings show that a strategy of combining heterologous antigen with self-antigens could produce a potent DNA vaccine that may be applicable to other tumor-associated antigens.
PMCID: PMC3947604  PMID: 20048073
16.  Characterization of Statin Dose-response within Electronic Medical Records 
Efforts to define the genetic architecture underlying variable statin response have met with limited success possibly because previous studies were limited to effect based on one-single-dose. We leveraged electronic medical records (EMRs) to extract potency (ED50) and efficacy (Emax) of statin dose-response curves and tested them for association with 144 pre-selected variants. Two large biobanks were used to construct dose-response curves for 2,026 (simvastatin) and 2,252 subjects (atorvastatin). Atorvastatin was more efficacious, more potent, and demonstrated less inter-individual variability than simvastatin. A pharmacodynamic variant emerging from randomized trials (PRDM16) was associated with Emax for both. For atorvastatin, Emax was 51.7 mg/dl in homozygous for the minor allele versus 75.0 mg/dl for those homozygous for the major allele. We also identified several loci associated with ED50. The extraction of rigorously defined traits from EMRs for pharmacogenetic studies represents a promising approach to further understand of genetic factors contributing to drug response.
PMCID: PMC3944214  PMID: 24096969
17.  Patients with Old Age or Proximal Tumors Benefit from Metabolic Syndrome in Early Stage Gastric Cancer 
PLoS ONE  2014;9(3):e89965.
Metabolic syndrome and/or its components have been demonstrated to be risk factors for several cancers. They are also found to influence survival in breast, colon and prostate cancer, but the prognostic value of metabolic syndrome in gastric cancer has not been investigated.
Clinical data and pre-treatment information of metabolic syndrome of 587 patients diagnosed with early stage gastric cancer were retrospectively collected. The associations of metabolic syndrome and/or its components with clinical characteristics and overall survival in early stage gastric cancer were analyzed.
Metabolic syndrome was identified to be associated with a higher tumor cell differentiation (P = 0.036). Metabolic syndrome was also demonstrated to be a significant and independent predictor for better survival in patients aged >50 years old (P = 0.009 in multivariate analysis) or patients with proximal gastric cancer (P = 0.047 in multivariate analysis). No association was found between single metabolic syndrome component and overall survival in early stage gastric cancer. In addition, patients with hypertension might have a trend of better survival through a good control of blood pressure (P = 0.052 in univariate analysis).
Metabolic syndrome was associated with a better tumor cell differentiation in patients with early stage gastric cancer. Moreover, metabolic syndrome was a significant and independent predictor for better survival in patients with old age or proximal tumors.
PMCID: PMC3943843  PMID: 24599168
18.  Evaluation of the Value of Fasting Plasma Glucose in the First Prenatal Visit to Diagnose Gestational Diabetes Mellitus in China 
Diabetes Care  2013;36(3):586-590.
To evaluate the value of fasting plasma glucose (FPG) value in the first prenatal visit to diagnose gestational diabetes mellitus (GDM).
Medical records of 17,186 pregnant women attending prenatal clinics in 13 hospitals in China, including the Peking University First Hospital (PUFH), were examined. Patients with pre-GDM were excluded; data for FPG at the first prenatal visit and one-step GDM screening with 75-g oral glucose tolerance test (OGTT) performed between 24 and 28 weeks of gestation were collected and analyzed.
The median ± SD FPG value was 4.58 ± 0.437. FPG decreased with increasing gestational age. FPG level at the first prenatal visit was strongly correlated with GDM diagnosed at 24–28 gestational weeks (χ2 = 959.3, P < 0.001). The incidences of GDM were 37.0, 52.7, and 66.2%, respectively, for women with FPG at the first prenatal visit between 5.10 and 5.59, 5.60 and 6.09, and 6.10–6.99 mmol/L. The data of PUFH were not statistically different from other hospitals.
Pregnant women (6.10 ≤ FPG < 7.00 mmol/L) should be considered and treated as GDM to improve outcomes; for women with FPG between 5.10 and 6.09 mmol/L, nutrition and exercise advice should be provided. An OGTT should be performed at 24–28 weeks to confirm or rule out GDM. Based on our data, we cannot support an FPG value ≥5.10 mmol/L at the first prenatal visit as the criterion for diagnosis of GDM.
PMCID: PMC3579369  PMID: 23193214
21.  A parthenogenetic maternal and double paternal contribution to an ovotesticular disorder of sex development 
An ovotesticular disorder of sex development (OT-DSD) was rarely found in human. The mechanism causing such condition is poorly understood. We hereby reported a 11-year-old child with OT-DSD and a karyotype 46,XX/46,XY, a single maternal and double paternal genetic contribution to the patient.
Fluorescence in situ hybridization (FISH), blood grouping, HLA (human leukocyte antigen) haplotyping and a genome-wide scanning of lymphocytes with 398 short tandem repeat microsatellite markers were performed to investigate the origin of the cell lines concerned. ABO typing revealed that two populations of red cells were in the patient, which were group A and group B, both from paternal alleles. HLA haplotyping showed the patient had three haplotypes. Haplotype 1 was inherited from maternity, haplotype 2 and 3 were from paternity. The STR microsatellite analysis showed 25 of the 74 fully informative markers in both parents, three alleles were inherited: one of them was from mother, another two were from father. Seventeen of the thirty-eight paternal markers, the patient inherited two paternal alleles. For 121 informative maternal markers, the patient had a single maternal allele. There were two distinct alleles in locus DXS6810 and DXS1073 on X-chromosome, in which one was from the mother and the other from the father.
The patient was a single maternal and double paternal genetic, which was a type of a parthenogenetic division of a maternal haploid nucleus into two identical nuclei, followed by fertilization by two spermatozoa and fusion of the two zygotes into a single individual at the early embryonic stage. To the best of our knowledge, this is the oldest OT-DSD case of parthenogenetic chimerism. These data provide additional evidence that a parthenogenetic maternal and double paternal contribution causes 46,XX/46,XY OT-DSD.
PMCID: PMC3974030  PMID: 24581244
Ovotesticular disorder of sex development; Parthenogenetic chimera; Molecular genetics
22.  The Prevalence and Molecular Spectrum of α- and β-Globin Gene Mutations in 14,332 Families of Guangdong Province, China 
PLoS ONE  2014;9(2):e89855.
To reveal the familial prevalence and molecular variation of α- and β-globin gene mutations in Guangdong Province.
A total of 40,808 blood samples from 14,332 families were obtained and analyzed for both hematological and molecular parameters.
A high prevalence of α- and β-globin gene mutations was found. Overall, 17.70% of pregnant women, 15.94% of their husbands, 16.03% of neonates, and 16.83% of couples (pregnant women and their husbands) were heterozygous carriers of α- or β-thalassemia. The regions with the highest prevalence were the mountainous and western regions, followed by the Pearl River Delta; the region with the lowest prevalence was Chaoshan. The total familial carrier rate (both spouses were α- or β-thalassemia carriers) was 1.87%, and the individual carrier rates of α- and β-thalassemia were 1.68% and 0.20%, respectively. The total rate of moderate-to-severe fetal thalassemia was 12.78% among couples in which both parents were carriers.
There was a high prevalence of α- and β-thalassemia in Guangdong Province. This study will contribute to the development of thalassemia prevention and control strategies in Guangdong Province.
PMCID: PMC3937408  PMID: 24587075
23.  Cystic breast lesions by conventional ultrasonography: sonographic subtype-pathologic correlation and BI-RADS Assessment 
Appropriate categorization is very important because the clinical management of each subtype of cystic breast lesions (CBLs) differs. The purpose was to evaluate the sonographic subtype-pathologic correlation, and to identify the effectiveness of the Breast Imaging Reporting and Data System (BI-RADS)-ultrasound (US) for differentiation of benign and malignant CBLs.
Material and methods
A database from December 1, 2007 and November 30, 2009 was identified in the Department of Diagnostic Ultrasound, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, China. Those patients with palpable or clinical symptomatic breast masses were associated with a cystic component in lesions on breast US. All patients underwent a subsequent fine-needle/core-needle biopsy or surgical excision. The sonographic findings were analyzed according to the BI-RADS-US, and were categorized by two different methods of subtype categorization compared with the pathologic results.
Ninety-nine breast cystic lesions in 83 women were included, among whom 16 patients were identified with bilateral cystic lesions. The total malignancy rate of CBLs was 14.1% (95% confidence interval 7.3–21.0%). Among 99 CBLs, 14 malignant lesions were associated with sonographic appearances of complex cystic lesions, while the remaining subtypes were benign. Shape, margin, echo pattern, orientation, calcification, and vascularity were statistically significantly different between the benign and malignant lesions (p = 0.010, p = 0.004, p < 0.001, p < 0.001, p = 0.036, and p < 0.001, respectively) (degrees of freedom = 1).
By comparison of the two different methods of subtype categorization of CBLs, the appropriate 5-variety classification should be suggested. The BI-RADS-US was useful for differentiating benign from malignant cystic lesions.
PMCID: PMC3953978
breast; ultrasonography; subtype; pathology; Breast Imaging Reporting and Data System
24.  Mechanical Stress Triggers Cardiomyocyte Autophagy through Angiotensin II Type 1 Receptor-Mediated p38MAP Kinase Independently of Angiotensin II 
PLoS ONE  2014;9(2):e89629.
Angiotensin II (Ang II) type 1 (AT1) receptor is known to mediate a variety of physiological actions of Ang II including autophagy. However, the role of AT1 receptor in cardiomyocyte autophagy triggered by mechanical stress still remains elusive. The aim of this study was therefore to examine whether and how AT1 receptor participates in cardiomyocyte autophagy induced by mechanical stresses. A 48-hour mechanical stretch and a 4-week transverse aorta constriction (TAC) were imposed to cultured cardiomyocytes of neonatal rats and adult male C57B/L6 mice, respectively, to induce cardiomyocyte hypertrophy prior to the assessment of cardiomyocyte autophagy using LC3b-II. Losartan, an AT1 receptor blocker, but not PD123319, the AT2 inhibitor, was found to significantly reduce mechanical stretch-induced LC3b-II upregulation. Moreover, inhibition of p38MAP kinase attenuated not only mechanical stretch-induced cardiomyocyte hypertrophy but also autophagy. To the contrary, inhibition of ERK and JNK suppressed cardiac hypertrophy but not autophagy. Intriguingly, mechanical stretch-induced autophagy was significantly inhibited by Losartan in the absence of Ang II. Taken together, our results indicate that mechanical stress triggers cardiomyocyte autophagy through AT1 receptor-mediated activation of p38MAP kinase independently of Ang II.
PMCID: PMC3931796  PMID: 24586922
25.  DNA-Gold Triangular Nanoprism Conjugates 
PMCID: PMC3930330  PMID: 19016498
anisotropic nanoparticles; DNA; gold; nanoparticle conjugates; nanoprisms

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