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1.  Application of immediate breast reconstruction with silicon prosthetic implantation following bilateral mammary gland excision in treatment of young patients with early breast cancer 
Journal of Thoracic Disease  2013;5(3):278-282.
To evaluate the application of immediate breast reconstruction (IBR) with silicon prosthetic implantation following bilateral nipple-preserving subcutaneous mammary gland excision in the treatment of young patients with early breast cancer.
We retrospectively analyzed the clinical data of 21 patients with breast cancer who were performed on IBR following bilateral nipple-preserving subcutaneous mammary gland excision in our hospital from January 2006 to March 2011.
The operations were successful in all the 21 patients. Also, the treatment provided a good cosmetic effect. No local recurrence or distant metastasis was found in these 21 patients during the 6-66-month follow-up.
For the young patients with early breast cancer, mammary gland excision on the affected side along with prophylactic excision of the contralateral side, namely IBR following bilateral nipple-preserving subcutaneous mammary gland excision, provides good clinical effectiveness and cosmetological effects.
PMCID: PMC3698255  PMID: 23825759
Breast cancer; prophylactic mastectomy; immediate breast reconstruction
2.  Resolving DNA at Efficiencies of More than A Million Plates per Meter Using Bare Narrow Open Capillary without Sieving Matrix 
We report a novel approach for effectively separating DNA molecules in free solution. The method uses a bare narrow open capillary without any sieving matrices to resolve a wide size-range of DNA fragments at efficiencies of more than a million plates per meter routinely.
PMCID: PMC3711670  PMID: 23459665
3.  Design of stapled α-helical peptides to specifically activate Wnt/β-catenin signaling 
Cell Research  2013;23(4):581-584.
PMCID: PMC3616433  PMID: 23439249
4.  Mononuclear nickel(II)-superoxo and nickel(III)-peroxo complexes bearing a common macrocyclic TMC ligand 
Mononuclear metal-dioxygen adducts, such as metal-superoxo and -peroxo species, are generated as key intermediates in the catalytic cycles of dioxygen activation by heme and non-heme metalloenzymes. We have shown recently that the geometric and electronic structure of the Ni-O2 core in [Ni(n-TMC)(O2)]+ (n = 12 and 14) varies depending on the ring size of the supporting TMC ligand. In this study, mononuclear Ni(II)-superoxo and Ni(III)-peroxo complexes bearing a common macrocylic 13-TMC ligand, such as [NiII(13-TMC)(O2)]+ and [NiIII(13-TMC)(O2)]+, were synthesized in the reaction of [NiII(13-TMC)(CH3CN)]2+ and H2O2 in the presence of tetramethylammonium hydroxide (TMAH) and triethylamine (TEA), respectively. The Ni(II)-superoxo and Ni(III)-peroxo complexes bearing the common 13-TMC ligand were successfully characterized by various spectroscopic methods, X-ray crystallography, and DFT calculations. Based on the combined experimental and theoretical studies, we conclude that the superoxo ligand in [NiII(13-TMC)(O2)]+ is bound in an end-on fashion to the nickel(II) center, whereas the peroxo ligand in [NiIII(13-TMC)(O2)]+ is bound in a side-on fashion to the nickel(III) center. Reactivity studies performed with the Ni(II)-superoxo and Ni(III)-peroxo complexes toward organic substrates reveal that the former possesses an electrophilic character, whereas the latter is an active oxidant in nucleophilic reaction.
PMCID: PMC3646059  PMID: 23662168
5.  Combination Therapy of Sorafenib and TACE for Unresectable HCC: A Systematic Review and Meta-Analysis 
PLoS ONE  2014;9(3):e91124.
Background and Aim
A large number of studies have tried to combine sorafenib with TACE for patients with unresectable hepatocellular carcinoma (HCC) and the results were controversial. We conducted this systematic review and meta-analysis to evaluate the safety and efficacy of combination therapy of sorafenib and TACE in the management of unresectable HCC.
MEDLINE, PsycINFO, Scopus, EMBASE, and the Cochrane Library were searched from January 1990 to October 2013 and these databases were searched for appropriate studies combining TACE and sorafenib in treatment of HCC. Two authors independently reviewed the databases and extracted the data and disagreements were resolved by discussion. Effective value and safety were analyzed. Effective value included disease control rate (DCR), time to progression (TTP) and overall survival (OS).
17 studies were included in the study. In the 10 noncomparative studies, DCR ranged from 18.4 to 91.2%. Median TTP ranged from 7.1 to 9.0 months, and median OS ranged from 12 to 27 months. In the 7 comparative studies, the hazard ratio (HR) for TTP was found to be 0.76 (95% CI 0.66–0.89; P<0.001) with low heterogeneity among studies (P = 0.243; I2 = 25.5%). However, the HR for OS was found to be 0.81 (95% CI 0.65–1.01; P = 0.061) with low heterogeneity among studies (P = 0.259; I2 = 25.4%). The common toxicities included fatigue, diarrhea, nausea, hand foot skin reaction (HFSR), hematological events, hepatotoxicity, alopecia, hepatotoxicity, hypertension and rash/desquamation. AEs are generally manageable with dose reductions.
Combination therapy may bring benefits for unresectable HCC patients in terms of TTP but not OS. Further well-designed randomized controlled studies are needed to confirm the efficacy of combination therapy.
PMCID: PMC3961236  PMID: 24651044
6.  Lack of Association of the TP53BP1 Glu353Asp Polymorphism with Risk of Cancer: A Systematic Review and Meta-Analysis 
PLoS ONE  2014;9(3):e90931.
The TP53BP1 gene may be involved in the development of cancer through disrupting DNA repair. However, studies investigating the relationship between TP53BP1 Glu353Asp (rs560191) polymorphism and cancer yielded contradictory and inconclusive outcomes. In order to realize these ambiguous findings, a meta-analysis was performed to assess the association between the TP53BP1 Glu353Asp (rs560191) polymorphism and susceptibility to cancer.
We conducted a search of all English reports on studies for the association between the TP53BP1 Asp353Glu (rs560191) polymorphism and susceptibility to cancer using Medline, the Cochrane Library, EMbase, Web of Science, Google (scholar), and all Chinese reports were identified manually and on-line using CBMDisc, Chongqing VIP database, and CNKI database. The strict selection criteria and exclusion criteria were determined, and odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. The fixed or random effect model was selected based on the heterogeneity test among studies. Publication bias was estimated using funnel plots and Egger’s regression test.
A total of seven studies were included in the meta-analysis including 3,213 cases and 3,849 controls. The results indicated that the Glu353Asp (rs560191) polymorphism in TP53BP1 gene had no association with cancer risk for all genetic models. In the subgroup analysis, the results suggested that Glu353Asp polymorphism was not associated with the risk of cancer according to ethnicity, cancer type, genotyping method, adjusted with control or not, HWE and quality score.
This meta-analysis suggested that the Glu353Asp (rs560191) polymorphism in TP53BP1 gene was not associated with risk of cancer.
PMCID: PMC3946247  PMID: 24603722
7.  Comparison of High-Spin and Low-Spin Non-heme FeIII–OOH Complexes in O–O Bond Homolysis and H-atom Abstraction Reactivities 
The geometric and electronic structures and reactivity of an S = 5/2 (HS) mononuclear non-heme (TMC)FeIII–OOH complex are studied by spectroscopies, calculations, and kinetics and compared with the results of previous studies of S = 1/2 (LS) FeIII–OOH complexes to understand parallels and differences in mechanisms of O–O bond homolysis and electrophilic H-atom abstraction reactions. The homolysis reaction of the HS [(TMC)FeIII–OOH]2+ complex is found to involve axial ligand coordination and a crossing to the LS surface for O–O bond homolysis. Both HS and LS FeIII–OOH complexes are found to perform direct H-atom abstraction reactions but with very different reaction coordinates. For the LS FeIII–OOH, the transition state is late in O–O and early in C–H coordinates. However, for the HS FeIII–OOH, the transition state is early in O–O and further along in the C–H coordinate. In addition, there is a significant amount of electron transfer from the substrate to the HS FeIII–OOH at transition state, but that does not occur in the LS transition state. Thus, in contrast to the behavior of LS FeIII–OOH, the H-atom abstraction reactivity of HS FeIII–OOH is found to be highly dependent on both the ionization potential and C–H bond strength of the substrate. LS FeIII–OOH is found to be more effective in H-atom abstraction for strong C–H bonds, while the higher reduction potential of HS FeIII–OOH allows it to be active in electrophilic reactions without the requirement of O–O bond cleavage. This is relevant to the Rieske dioxygenases, which are proposed to use a HS FeIII–OOH to catalyze cis-dihydroxylation of a wide range of aromatic compounds.
PMCID: PMC3614352  PMID: 23368958
8.  Stem Cell-Based Therapies for Ischemic Stroke 
BioMed Research International  2014;2014:468748.
In recent years, stem cell-based approaches have attracted more attention from scientists and clinicians due to their possible therapeutical effect on stroke. Animal studies have demonstrated that the beneficial effects of stem cells including embryonic stem cells (ESCs), inducible pluripotent stem cells (iPSCs), neural stem cells (NSCs), and mesenchymal stem cell (MSCs) might be due to cell replacement, neuroprotection, endogenous neurogenesis, angiogenesis, and modulation on inflammation and immune response. Although several clinical studies have shown the high efficiency and safety of stem cell in stroke management, mainly MSCs, some issues regarding to cell homing, survival, tracking, safety, and optimal cell transplantation protocol, such as cell dose and time window, should be addressed. Undoubtably, stem cell-based gene therapy represents a novel potential therapeutic strategy for stroke in future.
PMCID: PMC3955655  PMID: 24719869
9.  Comparison of Therapeutic Effects of Laparoscopic and Open Operation for Congenital Choledochal Cysts in Adults 
Background. Laparoscopic cyst excision and Roux-en-Y hepaticojejunostomy for treating congenital choledochal cysts (CCCs) have proved to be efficacious in children. Its safety and efficacy in adult patients remain unknown. The purpose of this study was to determine whether the laparoscopic procedure was feasible and safe in adult patients. Methods. We reviewed 35 patients who underwent laparoscopic operation (laparoscopic group) and 39 patients who underwent an open procedure (open group). The operative time, intraoperative blood loss, time until bowel motion recovery, duration of drainage, postoperative stay, time until resumption of diet, postoperative complications, and perioperative laboratory values were recorded and analyzed in both groups. Results. The operative time was longer in the laparoscopic group and decreased significantly with accumulating surgical experience (P < 0.01). The mean intraoperative blood loss was significantly lower in the laparoscopic group (P < 0.01). The time until bowel peristalsis recovery, time until resumption of diet, abdominal drainage, and postoperative stay were significantly shorter in the laparoscopic group (P < 0.01). The postoperative complication rate was not higher in the laparoscopic group than in the open group (P > 0.05). Conclusions. Laparoscopic cyst excision and hepaticojejunostomy are a feasible, effective, and safe method for treating CCCs in adult patients.
PMCID: PMC3955616  PMID: 24719612
10.  Decreased Seizure Threshold in an Eclampsia-Like Model Induced in Pregnant Rats with Lipopolysaccharide and Pentylenetetrazol Treatments 
PLoS ONE  2014;9(2):e89333.
Eclampsia is a poorly understood but potentially fatal complication of pregnancy. Research to date on this disorder has been hampered by the lack of a suitable animal model. To correct this deficiency, this report describes the generation of a rat eclampsia-like model using pentylenetetrazol (PTZ) in a previously established rat preeclampsia model.
Rats were administered lipopolysaccharide (1.0 µg/kg) by tail vein injection on gestational day 14 to establish preeclampsia (PE). PE and control rats (non-pregnant, NP; normal-pregnant, P) were injected intraperitoneally (i.p.) with PTZ (40 mg/kg) to induce seizures. In separate experiments, MgSO4 (270 mg/kg IP) was injected in advance of PTZ into PE rats to observe its effect on PTZ-induced seizures.
PE conditions were verified in rats after LPS administration by significantly higher blood pressure (P<0.01) and urinary albumin excretion (P<0.05), elevated sFlt-1 (P<0.05) and decreased PlGF serum levels (P<0.05), and evidence of hepatic dysfunction compared to control groups. PTZ successfully induced seizure activity in all groups studied. Latency to seizure was significantly (P<0.01) less in the PE-PTZ group (73.2±6.6 sec.) than in PTZ-treated controls (107.0±7.4 sec.). Pretreatment with MgSO4 prolonged (P<0.05) latency to seizure, shortened seizure duration and decreased seizure rates. Significant increased (P<0.05) in the serum levels of the inflammatory cytokines TNF-α and IL-1β in PE and PE-PTZ groups, and decreased (P<0.05) in their levels following MgSO4 administration.
This PTZ-induced eclampsia-like rat model is comparable to the human condition of eclampsia and may serve as a useful research tool for future studies of this disease. The increased inflammatory cytokines in preeclampsia are coincident with a decreased threshold for PTZ-induced seizures, suggesting that an inflammatory mechanism may contribute to the susceptibility to seizure activity and inflammation might have an important role in eclampsia.
PMCID: PMC3930732  PMID: 24586695
11.  The Self-Assembled Behavior of DNA Bases on the Interface 
A successful example of self-assembly in a biological system is that DNA can be an excellent agent to self-assemble into desirable two and three-dimensional nanostructures in a well-ordered manner by specific hydrogen bonding interactions between the DNA bases. The self-assembly of DNA bases have played a significant role in constructing the hierarchical nanostructures. In this review article we will introduce the study of nucleic acid base self-assembly by scanning tunneling microscopy (STM) at vacuum and ambient condition (the liquid/solid interface), respectively. From the ideal condition to a more realistic environment, the self-assembled behaviors of DNA bases are introduced. In a vacuum system, the energetic advantages will dominate the assembly formation of DNA bases, while at ambient condition, more factors such as conformational freedom and the biochemical environment will be considered. Therefore, the assemblies of DNA bases at ambient condition are different from the ones obtained under vacuum. We present the ordered nanostructures formed by DNA bases at both vacuum and ambient condition. To construct and tailor the nanostructure through the interaction between DNA bases, it is important to understand the assembly behavior and features of DNA bases and their derivatives at ambient condition. The utilization of STM offers the advantage of investigating DNA base self-assembly with sub-molecular level resolution at the surface.
PMCID: PMC3958828  PMID: 24473140
DNA base; self-assembly; interface chemistry; scanning tunneling microscopy
12.  Prognostic Role of MicroRNA-210 in Various Carcinomas: A Systematic Review and Meta-Analysis 
Disease Markers  2014;2014:106197.
Objective. Many studies have shown that microRNAs (miRNAs) could play a potential role as prognostic biomarkers of tumors. The aim of this study is to summarize the global predicting role of microRNA-210 (miR-210) for survival in patients with a variety of carcinomas. Methods. Relevant literature was identified using PubMed and the information in eligible studies has been extracted. Then meta-analysis of hazard ratio (HR) was performed to evaluate the prognostic role of the miR-210 in different tumors. Results. This meta-analysis included 9 published studies dealing with various carcinomas. For recurrence free survival or disease free survival (RFS/DFS), the combined hazard ratio (HR) and 95% confidence interval (95% CI) of higher miR-210 expression were 2.47 [1.36, 4.46], which could significantly predict poor survival in general carcinomas. MicroRNA-210 was also a significant predictor for overall survival (OS), metastasis free survival or distant relapse free survival (MFS/DRFS), and disease specific survival (DSS). Importantly, subgroup analysis suggested that higher expression of miR-210 correlated with worse RFS/DFS, OS, and MFS/DRFS, especially in breast cancer, which were 3.36 [2.30, 4.93], 3.29 [1.65, 6.58], and 2.85 [1.76, 4.62] separately. Conclusion. Our studies suggested that microRNA-210 could predict the outcome of patients with varieties of tumors, especially in breast cancers.
PMCID: PMC3925626  PMID: 24591754
13.  MicroRNA-143 Regulates Adipogenesis by Modulating the MAP2K5–ERK5 Signaling 
Scientific Reports  2014;4:3819.
A better understanding of the molecular mechanisms that regulate adipose tissue-derived stromal cell (ADSC) differentiation could provide new insight into some adipose-tissue-related disease. The differentiation of ADSCs into adipocytes is a complex physiological process that includes clonal expansion, growth arrest, and terminal differentiation. Here the role of microRNA-143 (miR-143) during ADSC adipogenic differentiation was systematically investigated. We found that miR-143 expression was transiently decreased after adipogenic induction while increased from day 3 and peaked on day 7 after induction. We show for the first time that the role of miR-143 is not consistent in the differentiation process. The regulatory role depends on the differentiation stage that miR-143 acts on. When miR-143 is overexpressed during the clonal expansion stage, the adipogenic differentiation of ADSCs is inhibited, whereas the overexpression of miR-143 during the growth arrest stage or terminal differentiation stage promotes differentiation. Further we firstly demonstrate that miR-143 plays the modulational role by directly repressing MAP2K5, a key member of the MAPKK family in the MAPK signaling pathway. These findings suggest that miR-143 plays an important role in adipose tissue formation, with special implications for some metabolic disease in which the amount and/or function of adipose tissue is altered.
PMCID: PMC3897956  PMID: 24448661
14.  Olig2 Targets Chromatin Remodelers To Enhancers To Initiate Oligodendrocyte Differentiation 
Cell  2013;152(1-2):248-261.
Establishment of oligodendrocyte identity is crucial for subsequent events of myelination in the central nervous system (CNS). Here, we demonstrate that activation of ATP-dependent SWI/SNF chromatin-remodeling enzyme Smarca4/Brg1 at the differentiation onset is necessary and sufficient to initiate and promote oligodendrocyte lineage progression and maturation. Genome-wide multistage studies by ChIP-seq reveal that oligodendrocyte-lineage determination factor Olig2 functions as a pre-patterning factor to direct Smarca4/Brg1 to oligodendrocyte-specific enhancers. Recruitment of Smarca4/Brg1 to distinct subsets of myelination regulatory genes is developmentally regulated. Functional analyses of Smarca4/Brg1 and Olig2 co-occupancy relative to chromatin epigenetic marking uncover novel stage-specific cis-regulatory elements that predict sets of transcriptional regulators controlling oligodendrocyte differentiation. Together, our results demonstrate that regulation of the functional specificity and activity of a Smarca4/Brg1-dependent chromatin-remodeling complex by Olig2, coupled with transcriptionally-linked chromatin modifications, is critical to precisely initiate and establish the transcriptional program that promotes oligodendrocyte differentiation and subsequent myelination of the CNS.
PMCID: PMC3553550  PMID: 23332759
16.  Comparison of Riboflavin/Ultraviolet-A Cross-Linking in Porcine, Rabbit, and Human Sclera 
BioMed Research International  2014;2014:194204.
Purpose. To compare the biomechanical properties of porcine, rabbit, and human sclera before and after riboflavin/ultraviolet-A (UVA) collagen cross-linking (CXL). Methods. Eight rabbits, 8 porcine eyeballs, and 8 human eyeballs were included. One rabbit eye and half of each bisected human and porcine eyeball were treated with riboflavin/UVA CXL. Untreated fellow rabbit eyes and eyeball halves served as controls. A 10 mm × 20 mm scleral band was harvested from each specimen. From this band, two 3.5 mm × 15.0 mm strips were prepared for biomechanical testing. The biomechanical parameters were ultimate stress, stress and Young's modulus. Results. Values of stress, and Young's modulus showed that human sclera was 4 times stiffer than porcine sclera and 3 times stiffer than rabbit sclera. In rabbit sclera, both the stress and Young's modulus were significantly increased by CXL (P < 0.05). In porcine sclera, only the ultimate stress was significantly increased by CXL (P < 0.05). The biomechanical properties of human sclera were not statistically affected by CXL (P > 0.05). Conclusions. Human sclera has higher biomechanical stiffness than porcine and rabbit sclera. With the same irradiation dose, riboflavin/UVA CXL increases the biomechanical stiffness of rabbit sclera but not porcine or human sclera.
PMCID: PMC3910020  PMID: 24527438
17.  Limited Gene Expression Variation in Human Embryonic Stem Cell and Induced Pluripotent Stem Cell Derived Endothelial Cells 
Stem cells (Dayton, Ohio)  2013;31(1):92-103.
Recent evidence suggests human embryonic stem (ES) and induced pluripotent stem (iPS) cell lines have differences in their epigenetics marks and transcriptomes, yet the impact of these differences on subsequent terminally differentiated cells is less well understood. Comparison of purified, homogeneous populations of somatic cells derived from multiple independent human iPS and ES lines will be required to address this critical question. Here, we report a differentiation protocol based on embryonic development that consistently yields large numbers of endothelial cells (EC) derived from multiple human ES or iPS cells. Mesoderm differentiation of embryoid bodies was maximized and defined growth factors were used to generate KDR+ EC progenitors. Magnetic purification of a KDR+ progenitor subpopulation resulted in an expanding, homogeneous pool of ECs that expressed EC markers and had functional properties of ECs. Comparison of the transcriptomes revealed limited gene expression variability between multiple lines of human iPS–derived ECs, or between lines of ES– and iPS–derived ECs. These results demonstrate a method to generate large numbers of pure human EC progenitors and differentiated ECs from pluripotent stem cells, and suggest individual lineages derived from human iPS cells may have significantly less variance than their pluripotent founders.
PMCID: PMC3528812  PMID: 23079999
Endothelial Cells; Stem Cells; Induced Pluripotent Stem Cells; Cell Differentiation
18.  Effects of Experimental Nitrogen and Phosphorus Addition on Litter Decomposition in an Old-Growth Tropical Forest 
PLoS ONE  2013;8(12):e84101.
The responses of litter decomposition to nitrogen (N) and phosphorus (P) additions were examined in an old-growth tropical forest in southern China to test the following hypotheses: (1) N addition would decrease litter decomposition; (2) P addition would increase litter decomposition, and (3) P addition would mitigate the inhibitive effect of N addition. Two kinds of leaf litter, Schima superba Chardn. & Champ. (S.S.) and Castanopsis chinensis Hance (C.C.), were studied using the litterbag technique. Four treatments were conducted at the following levels: control, N-addition (150 kg N ha−1 yr−1), P-addition (150 kg P ha−1 yr−1) and NP-addition (150 kg N ha−1 yr−1 plus 150 kg P ha−1 yr−1). While N addition significantly decreased the decomposition of both litters, P addition significantly inhibited decomposition of C.C., but did not affect the decomposition of S.S. The negative effect of N addition on litter decomposition might be related to the high N-saturation in this old-growth tropical forest; however, the negative effect of P addition might be due to the suppression of “microbial P mining”. Significant interaction between N and P addition was found on litter decomposition, which was reflected by the less negative effect in NP-addition plots than those in N-addition plots. Our results suggest that P addition may also have negative effect on litter decomposition and that P addition would mitigate the negative effect of N deposition on litter decomposition in tropical forests.
PMCID: PMC3877223  PMID: 24391895
19.  Oxidative stress induces gastric submucosal arteriolar dysfunction in the elderly 
AIM: To evaluate human gastric submucosal vascular dysfunction and its mechanism during the aging process.
METHODS: Twenty male patients undergoing subtotal gastrectomy were enrolled in this study. Young and elderly patient groups aged 25-40 years and 60-85 years, respectively, were included. Inclusion criteria were: no clinical evidence of cardiovascular, renal or diabetic diseases. Conventional clinical examinations were carried out. After surgery, gastric submucosal arteries were immediately dissected free of fat and connective tissue. Vascular responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were measured by isolated vascular perfusion. Morphological changes in the gastric mucosal vessels were observed by hematoxylin and eosin (HE) staining and Verhoeff van Gieson (EVG) staining. The expression of xanthine oxidase (XO) and manganese-superoxide dismutase (Mn-SOD) was assessed by Western blotting analysis. The malondialdehyde (MDA) and hydrogen peroxide (H2O2) content and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined according to commercial kits.
RESULTS: The overall structure of vessel walls was shown by HE and EVG staining, respectively. Disruption of the internal elastic lamina or neointimal layers was not observed in vessels from young or elderly patients; however, cell layer number in the vessel wall increased significantly in the elderly group. Compared with submucosal arteries in young patients, the amount of vascular collagen fibers, lumen diameter and media cross-sectional area were significantly increased in elderly patients. Ach- and SNP-induced vasodilatation in elderly arterioles was significantly decreased compared with that of gastric submucosal arterioles from young patients. Compared with the young group, the expression of XO and the contents of MDA and H2O2 in gastric submucosal arterioles were increased in the elderly group. In addition, the expression of Mn-SOD and the activities of SOD and GSH-Px in the elderly group decreased significantly compared with those in the young group.
CONCLUSION: Gastric vascular dysfunction and senescence may be associated with increased oxidative stress and decreased antioxidative defense in the aging process.
PMCID: PMC3882420  PMID: 24409074
Aging; Vascular dysfunction; Gastric blood flow; Oxidative stress; Human
20.  Prevalence of ocular fundus pathology with type 2 diabetes in a Chinese urban community as assessed by telescreening 
BMJ Open  2013;3(12):e004146.
To describe the telescreening model and assess the prevalence of ocular fundus pathology in patients with type 2 diabetes within a Chinese urban community.
Community-based cross-sectional study.
Healthcare centre of Fengyutan Community, Shenyang, China.
A total 528 patients (287 females) with type 2 diabetes mellitus (DM) were randomly recruited using health files from the healthcare centre of Fengyutan community between 8 October and 20 November 2012.
Main outcome measures
Signs of any diabetic retinopathy (DR), signs of glaucoma and signs of age-related macular degeneration (AMD).
The main ocular fundus pathologies were DR (75 patients, 14.20%), 65 (86.67%) cases of which were newly detected, AMD (57 patients, 10.79%) and glaucoma (63 patients, 11.93%). The risk factors for fundus pathology were long duration of diabetes (OR 2.31, 95% CI 1.87 to 2.56), and higher fasting plasma glucose (OR 3.64, 95% CI 1.81 to 5.21) and glycated haemoglobin (HbA1c) levels (OR 3.83, 95% CI 1.87 to 6.35).
There was a high prevalence of fundus pathology among patients with type 2 diabetes, and in most of the cases, this was newly detected. Community screening for fundus pathology among patients with a long duration of type 2 diabetes and high fasting plasma glucose and HbA1c levels using a telescreening model will provide an effective strategy for the prevention and treatment of fundus pathology.
PMCID: PMC3884592  PMID: 24381259
21.  MicroRNA-217 Promotes Angiogenesis of Human Cytomegalovirus-Infected Endothelial Cells through Downregulation of SIRT1 and FOXO3A 
PLoS ONE  2013;8(12):e83620.
Human cytomegalovirus(HCMV) infection has been shown to contribute to vascular disease through the induction of angiogenesis. However, the role of microRNA in angiogenesis induced by HCMV infection remains unclear. The present study was thus designed to explore the potential effect of miR-1217 on angiogenesis and to disclose the underlying mechanism in endothelial cells. We found that HCMV infection of endothelial cells(ECs) enhanced expression of miR-217 and reduced SIRT1 and FOXO3A protein level in 24 hours post infection(hpi). Transfection of miR-217 inhibitor not only depressed cellular migration and tube formation induced by HCMV infection, but also enhanced SIRT1 and FOXO3A protein expression. Additionally, luciferase assay confirmed that miR-217 directly targeted FOXO3A mRNA 3`UTR. Furthermore, pretreatment with resveratrol depressed motility and tube formation of HCMV-infected ECs, which could be reversed by SIRT1 siRNA. Similarly, delivery of FOXO3A overexpression lentivirus suppressed proliferative rate, migration and tube formation of HCMV-infected ECs, which reversed by transfection of FOXO3A siRNA. In summary, HCMV infection of endothelial cells induces angiogenesis by both of miR-217/SIRT1 and miR-217/FOXO3A axis.
PMCID: PMC3869804  PMID: 24376725
22.  The Value of Emotion: How Does Episodic Prospection Modulate Delay Discounting? 
PLoS ONE  2013;8(11):e81717.
Humans often show impatience when making intertemporal choice for monetary rewards, preferring small rewards delivered immediately to larger rewards delivered after a delay, which reflects a fundamental psychological principle: delay discounting. However, we propose that episodic prospection humans can vividly envisage exerts a strong and broad influence on individuals' delay discounting. Specifically, episodic prospection may affect individuals' intertemporal choice by the negative or positive emotion of prospection.
Methodology/Principal Findings
The present study explored how episodic prospection modulated delay discounting by emotion. Study 1 showed that participants were more inclined to choose the delayed but larger rewards when they imaged positive future events than when they did not image events; Study 2 showed that participants were more inclined to choose the immediate but smaller rewards when they imaged negative future events than when they did not image events; In contrast, study 3 showed that choice preferences of participants when they imaged neutral future events were the same as when they did not image events.
By manipulating the emotion valence of episodic prospection, our findings suggested that positive emotion made individuals tend to choose delayed rewards, while negative emotion made individuals tend to choose immediate rewards. Only imaging events with neutral emotion did not affect individuals' choice preference. Thus, the valence of imaged future events' emotion might play an important role in individuals' intertemporal choice. It is possible that the valence of emotion may affect the changed direction (promote or inhibit) of individuals' delay discounting, while the ability to image future events affects the changed degree of individuals' delay discounting.
PMCID: PMC3842935  PMID: 24312341
23.  A New Biomarkers Feature Pattern Consisting of TNF-α, IL-10, and IL-8 for Blood Stasis Syndrome with Myocardial Ischemia 
Objective. To explore new diagnostic patterns for syndromes to overcome the insufficiency of obtainable macrocharacteristics and specific biomarkers. Methods. Chinese miniswines were subjected to Ameroid constrictor, placed around the proximal left anterior descending branch. On the 4th week, macrocharacteristics, coronary angiography, echocardiography, and hemorheology indices were detected for diagnosis. IL-1, IL-6, IL-8, IL-10, TNF-α, and hsCRP in serum were detected, and Decision Tree was built. Results. According to current official-issued standard, model animals matched the diagnosis of blood stasis syndrome with myocardial ischemia based on findings, including >90% occlusion, attenuated left ventricular segmental motion, dark red or purple tongues, and higher blood viscosity. Significant decrease of IL-10 and increase of TNF-α were found in model animals. However, in the Decision Tree, besides IL-10 and TNF-α, IL-8 helped to increase the accuracy of classification to 86%. Conclusions. The Decision Tree building with TNF-α, IL-10, and IL-8 is helpful for the diagnosis of blood stasis syndrome in myocardial ischemia animals. What is more is that our data set up a new path to the differentiation of syndrome by feature patterns consisting of multiple biomarkers not only for animals but also for patients. We believe that it will contribute to the standardization and international application of syndromes.
PMCID: PMC3859256  PMID: 24371451
24.  DCGL v2.0: An R Package for Unveiling Differential Regulation from Differential Co-expression 
PLoS ONE  2013;8(11):e79729.
Differential co-expression analysis (DCEA) has emerged in recent years as a novel, systematic investigation into gene expression data. While most DCEA studies or tools focus on the co-expression relationships among genes, some are developing a potentially more promising research domain, differential regulation analysis (DRA). In our previously proposed R package DCGL v1.0, we provided functions to facilitate basic differential co-expression analyses; however, the output from DCGL v1.0 could not be translated into differential regulation mechanisms in a straightforward manner.
To advance from DCEA to DRA, we upgraded the DCGL package from v1.0 to v2.0. A new module named “Differential Regulation Analysis” (DRA) was designed, which consists of three major functions: DRsort, DRplot, and DRrank. DRsort selects differentially regulated genes (DRGs) and differentially regulated links (DRLs) according to the transcription factor (TF)-to-target information. DRrank prioritizes the TFs in terms of their potential relevance to the phenotype of interest. DRplot graphically visualizes differentially co-expressed links (DCLs) and/or TF-to-target links in a network context. In addition to these new modules, we streamlined the codes from v1.0. The evaluation results proved that our differential regulation analysis is able to capture the regulators relevant to the biological subject.
With ample functions to facilitate differential regulation analysis, DCGL v2.0 was upgraded from a DCEA tool to a DRA tool, which may unveil the underlying differential regulation from the observed differential co-expression. DCGL v2.0 can be applied to a wide range of gene expression data in order to systematically identify novel regulators that have not yet been documented as critical.
DCGL v2.0 package is available at or at our project home page
PMCID: PMC3835854  PMID: 24278165
25.  Geographical prevalence and risk factors for pterygium: a systematic review and meta-analysis 
BMJ Open  2013;3(11):e003787.
Pterygium is considered to be a proliferative overgrowth of bulbar conjunctiva that can induce significant astigmatism and cause visual impairment; this is the first meta-analysis to investigate the pooled prevalence and risk factors for pterygium in the global world.
A systematic review and meta-analysis of population-based studies.
A total of 20 studies with 900 545 samples were included.
Primary outcome measure
The pooled prevalence and risk factors for pterygium.
20 studies were included. The pooled prevalence of pterygium was 10.2% (95% CI 6.3% to 16.1%). The pooled prevalence among men was higher than that among women (14.5% vs 13.6%). The proportion of participants with unilateral cases of pterygium was higher than that of participants with bilateral cases of pterygium. We found a trend that the higher pooled prevalence of pterygium was associated with increasing geographical latitude and age in the world. The pooled OR was 2.32 (95% CI 1.66 to 3.23) for the male gender and 1.76 (95% CI 1.55 to 2.00) for outdoor activity, respectively.
The pooled prevalence of pterygium was relatively high, especially for low latitude regions and the elderly. There were many modifiable risk factors associated with pterygium to which healthcare providers should pay more attention.
PMCID: PMC3840351  PMID: 24253031
Epidemiology; Ophthalmology

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