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1.  Association between alpha-fetoprotein and metabolic syndrome in a Chinese asymptomatic population: a cross-sectional study 
Metabolic syndrome is closely associated with an increased risk for fatty liver disease morbidity and mortality. Recently, studies have reported that participants with fatty liver disease have higher serum alpha-fetoprotein levels than those without. We investigated the association between alpha-fetoprotein levels and the prevalence of metabolic syndrome in a Chinese asymptomatic population.
A cross-sectional study was performed with 7 755 participants who underwent individual health examinations. Clinical and anthropometric parameters were collected and serum alpha-fetoprotein levels and other clinical and laboratory parameters were measured. Logistic regression analysis was used to examine associations between alpha-fetoprotein and metabolic syndrome.
Participants with metabolic syndrome had significantly higher (p < 0.001) alpha-fetoprotein levels than those without, though all alpha-fetoprotein levels were within the reference interval. The association between the components of metabolic syndrome (central obesity, elevated blood pressure, elevated triglycerides, reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose) and alpha-fetoprotein levels was evaluated. Alpha-fetoprotein levels in the elevated triglycerides, reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose groups were significantly different (p=0.002, p < 0.001, p=0.020) compared with alpha-fetoprotein in the normal triglycerides, high-density lipoprotein cholesterol, and fasting plasma glucose groups. Logistic regression analyses showed an association between alpha-fetoprotein levels and increased risk for metabolic syndrome, the presence of reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose, but not with obesity, elevated blood pressure, or triglycerides.
These results suggest a significant association between alpha-fetoprotein and metabolic syndrome.
PMCID: PMC4848775  PMID: 27121855
Alpha-fetoprotein; Metabolic syndrome; Fatty liver disease
2.  Finding Communities by Their Centers 
Scientific Reports  2016;6:24017.
Detecting communities or clusters in a real-world, networked system is of considerable interest in various fields such as sociology, biology, physics, engineering science, and interdisciplinary subjects, with significant efforts devoted in recent years. Many existing algorithms are only designed to identify the composition of communities, but not the structures. Whereas we believe that the local structures of communities can also shed important light on their detection. In this work, we develop a simple yet effective approach that simultaneously uncovers communities and their centers. The idea is based on the premise that organization of a community generally can be viewed as a high-density node surrounded by neighbors with lower densities, and community centers reside far apart from each other. We propose so-called “community centrality” to quantify likelihood of a node being the community centers in such a landscape, and then propagate multiple, significant center likelihood throughout the network via a diffusion process. Our approach is an efficient linear algorithm, and has demonstrated superior performance on a wide spectrum of synthetic and real world networks especially those with sparse connections amongst the community centers.
PMCID: PMC4823754  PMID: 27053090
3.  Insomnia Symptom, Mental Disorder and Suicide: A Case-Control Study in Chinese Rural Youths 1 
Sleep and biological rhythms  2015;13(2):181-188.
Insomnia has been reported as a risk factor of suicidal behaviors, but few studies have examined the association among insomnia, mental disorder and suicide, especially among Chinese populations. In this study, we examined the effect of insomnia symptoms on completed suicide in a large sample of suicides and their controls in Chinese rural youths. Subjects were 388 consecutively recruited suicides and 416 community living controls aged 15–34 years in the rural areas of three provinces in China. Established psychological autopsy method was used for the data collection. Insomnia symptoms were assessed with sleep questions in the Hamilton Depression Rating Scale (HAMD) about insomnia, including difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS) and early morning awakening (EMA). The results showed that DIS (OR=12.01, p<0.001), DMS (OR=12.82, p<0.001) or EMA (OR=12.08, p<0.001) was significantly associated with increased risk of suicide even after mental disorder was controlled for. Our study showed that insomnia can be an independent risk factor for suicide. Mental disorders mediated the association between insomnia and suicide. Insomnia should be assessed and treated for individuals at risk of suicide.
PMCID: PMC4405250  PMID: 25914606
Insomnia; mental disorder; suicide; case-control study; China
4.  DXA utilization between 2006 and 2012 in commercially insured younger postmenopausal women 
Reimbursement for dual energy x-ray absorptiometry (DXA) scans in the outpatient setting has declined significantly since 2006. Research through 2011 has suggested reimbursement reductions for DXA scans have corresponded with an overall decreased utilization of DXA. This study updates utilization estimates for DXAs through 2012 in patients with commercial insurance and compares DXA rates before and after reimbursement changes.
We evaluated DXA utilization for women age 50–64 from Marketscan Commercial Claims and Encounter database between January 2006 and December 2012 based on CPT codes. We estimated utilization rates per 1,000 person years. We also employed segmented regression analysis of monthly rates to evaluate the change in utilization rates after a proposed reimbursement reduction in July 2009.
In women aged 50–64; 451,656 DXAs were performed in 2006, a rate of 144 DXAs per 1,000 person years. This rate increased to 149 DXAs per 1,000 person years in 2009 before decreasing to 110 DXAs per 1,000 person years or 667,982 scans in 2012. DXA utilization increased by 2.24 per 1,000 person years until July 2009 then declined by 12.98 DXAs per 1,000 persons, resulting in 37.5 DXAs per person year fewer performed in 2012 compared to 2006.
Since July 2009 a significant decline in DXA utilization occurred in a younger postmenopausal commercially insured population. This decline corresponds with a time period of reductions in Medicare DXA reimbursement.
PMCID: PMC4420644  PMID: 25700662
Dual energy x-ray absorptiometry (DXA); Reimbursement; Utilization; Osteoporosis
5.  The Relationship between Impulsivity and Suicide Among Rural Youths Aged 15–35 Years: A Case-Control Psychological Autopsy Study1 
Psychology, health & medicine  2015;21(3):330-337.
In China, the gender ratio of suicide rates did not match the Western patterns, which was higher for females than males. However, the rural men were at relatively high risk of suicide in Liaoning province. Impulsivity was an important factor of suicide behaviors, but there was a lack of studies in China. This research aimed to study the relationship between impulsive personality traits and suicidal behavior among Chinese rural youths. Suicides were consecutively sampled from six randomly selected counties in Liaoning Province in China. Between 2005 and 2007, a total of 162 suicide victims were enrolled in the study along with 162 community controls matched for age, gender, and location. The psychological autopsy method was used to collect data from informants knowledgeable about the selected suicide victims and controls. The results showed the suicide victims in the study were more likely to demonstrate dysfunctional impulsivity and less likely to demonstrate functional impulsivity compared with the controls. Mental disorders, acute negative life events and dysfunctional impulsivity contributed to the risk of suicide; educational and functional impulsivity were protective factors. Suicide prevention efforts in rural China may address impulsivity.
PMCID: PMC4691212  PMID: 26110614
Suicide; Impulsivity; Life Events; Mental Disorder; Psychological Autopsy; China
6.  Cleaning up after ICH: the role of Nrf2 in modulating microglia function and hematoma clearance 
Journal of neurochemistry  2014;133(1):144-152.
As a consequence of intracerebral hemorrhage (ICH), blood components enter brain parenchyma causing progressive damage to the surrounding brain. Unless hematoma is cleared, the reservoirs of blood continue to inflict injury to neurovascular structures and blunt the brain repair processes. Microglia/macrophages (MM Φ) represent the primary phagocytic system that mediates the cleanup of hematoma. Thus the efficacy of phagocytic function by MM Φ is an essential step in limiting ICH-mediated damage. By using primary microglia to model red blood cell (main component of hematoma) clearance, we studied the role of transcription factor Nrf2, a master-regulator of anti-oxidative defense, in the hematoma clearance process. We showed that in cultured microglia, activators of Nrf2 1) induce anti-oxidative defense components, 2) reduce peroxide formation, 3) upregulate phagocytosis-mediating scavenger receptor CD36, and 4) enhance RBC phagocytosis. Through inhibiting Nrf2 or CD36 in microglia, by DNA-decoy or neutralizing antibody, we documented the important role of Nrf2 and CD36 in RBC phagocytosis. Using autologous blood injection ICH model to measure hematoma resolution, we showed that Nrf2 activator, sulforaphane, injected to animals after the onset of ICH, induced CD36 expression in ICH-affected brain and improved hematoma clearance in rats and wild-type mice, but expectedly not in Nrf2-knockout-(KO) mice. Normal hematoma clearance was impaired in Nrf2-KO mice. Our experiments suggest that Nrf2 in microglia play an important role in augmenting the anti-oxidative capacity, phagocytosis and hematoma clearance after ICH.
PMCID: PMC4361377  PMID: 25328080
intracerebral hemorrhage; Nrf2; sulforaphane; microglia; phagocytosis; hematoma
7.  Identification of bacterial communities in sediments of Poyang Lake, the largest freshwater lake in China 
SpringerPlus  2016;5:401.
Bacteria play a vital role in various biogeochemical processes in lacustrine sediment ecosystems. This study is among the first to investigate the spatial distribution patterns of bacterial community composition in the sediments of Poyang Lake, the largest freshwater lake of China. Sediment samples were collected from the main basins and mouths of major rivers that discharge into the Poyang Lake in May 2011. Quantitative PCR assay and pyrosequencing analysis of 16S rRNA genes showed that the bacteria community abundance and compositions of Poyang Lake sediment varied largely among sampling sites. A total of 25 phyla and 68 bacterial orders were distinguished. Burkholderiales, Gallionellales (Beta-proteobacteria), Myxococcales, Desulfuromonadales (Delta-proteobacteria), Sphingobacteriales (Bacteroidetes), Nitrospirales (Nitrospirae), Xanthomonadales (Gamma-proteobacteria) were identified as the major taxa and collectively accounted for over half of annotated sequences. Moreover, correlation analyses suggested that higher loads of total phosphorus and heavy metals (copper, zinc and cadmium) could enhance bacterial abundance in the sediment.
Electronic supplementary material
The online version of this article (doi:10.1186/s40064-016-2026-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4816951  PMID: 27047727
Bacterial community; Sediment; Poyang Lake; High-throughput sequencing
8.  Community Size Effects on Epidemic Spreading in Multiplex Social Networks 
PLoS ONE  2016;11(3):e0152021.
The dynamical process of epidemic spreading has drawn much attention of the complex network community. In the network paradigm, diseases spread from one person to another through the social ties amongst the population. There are a variety of factors that govern the processes of disease spreading on the networks. A common but not negligible factor is people’s reaction to the outbreak of epidemics. Such reaction can be related information dissemination or self-protection. In this work, we explore the interactions between disease spreading and population response in terms of information diffusion and individuals’ alertness. We model the system by mapping multiplex networks into two-layer networks and incorporating individuals’ risk awareness, on the assumption that their response to the disease spreading depends on the size of the community they belong to. By comparing the final incidence of diseases in multiplex networks, we find that there is considerable mitigation of diseases spreading for full phase of spreading speed when individuals’ protection responses are introduced. Interestingly, the degree of community overlap between the two layers is found to be critical factor that affects the final incidence. We also analyze the consequences of the epidemic incidence in communities with different sizes and the impacts of community overlap between two layers. Specifically, as the diseases information makes individuals alert and take measures to prevent the diseases, the effective protection is more striking in small community. These phenomena can be explained by the multiplexity of the networked system and the competition between two spreading processes.
PMCID: PMC4805200  PMID: 27007112
9.  Altered function of monocytes/macrophages in patients with autoimmune hepatitis 
Molecular Medicine Reports  2016;13(5):3874-3880.
The pathogenesis of autoimmune hepatitis (AIH) involves the intervention of the innate and adaptive immune responses. In the current study, the alterations in monocytes/Kupffer cells (KCs) were investigated in patients with AIH. A total of 21 patients with AIH at different stages of the disease, and 7 controls with non-alcoholic fatty liver disease were selected. The abundance of VAV1 and p21-activated kinase 1 (PAK1) in the liver and KCs was analyzed. In addition, the expression levels of HLA-DR and CD80 in the peripheral blood monocytes (PBMs) were measured, and phagocytosis of PBMs was assessed. KCs of AIH patients exhibited higher expression levels of VAV1 and PAK1. This upregulated expression was associated with disease progression. A reduced expression of HLA-DR and CD80, and reduced capacity of E. coli phagocytosis in PBMs was observed for patients with AIH. This downregulated expression was associated with disease progression. The results of the current study indicated that defective function of KCs and PBMs may be involved in the pathogenesis of AIH.
PMCID: PMC4838131  PMID: 26986756
autoimmune hepatitis; Kupffer cells; peripheral blood monocytes; VAV1
10.  Self-assembled hydrophobin for producing water-soluble and membrane permeable fluorescent dye 
Scientific Reports  2016;6:23061.
Low water solubility and poor membrane permeability are major disadvantages that compromise applications of most fluorescent dyes. To resolve these problems, herein, using Boron-dipyrromethene (BODIPY) as a model fluorescent dye, for the first time, we provide a new strategy for the rapid and efficient production of a water-soluble and membrane-permeable dye by mixing with an amphiphilic protein named hydrophobin. Data shows BODIPY could be effectively solubilized and dispersed in 200 μg/mL hydrophobin by simple mixing and sonication. Subsequent experiments indicated that hydrophobin self-assembled into a protein film on the surface of BODIPY forming stable hydrophobin-BODIPY complexes with a size range of 10–30 nm. Furthermore, we demonstrated hydrophobin-functionalized BODIPY are toxicity free to cells. The hydrophobin-BODIPY complex could pass through both the cell plasma membrane and nuclear membrane efficiently. Our work opens a novel route to modify and functionalize fluorescent dyes and may be developed as a general strategy for broadening their applications.
PMCID: PMC4791660  PMID: 26976627
11.  Prevalence of diabetes and determinants: evidence from a minority region in People’s Republic of China 
This study aimed to examine the prevalence of diabetes mellitus and other categories of glucose intolerance (impaired glucose tolerance and impaired fasting glucose) and explore the risk factors in an ethnic minority region, Guangxi Zhuang Autonomous Region, People’s Republic of China.
A population-based study enrolled 53,270 residents older than 5 years in Guangxi, People’s Republic of China. The prevalence of diabetes was calculated using the 1999 World Health Organization (WHO) oral glucose tolerance test diagnostic criteria.
Among 53,270 individuals, the prevalence of diabetes, impaired glucose tolerance, and impaired fasting glucose was 5.96%, 7.36%, and 2.62%, respectively. Of the 3,173 individuals with diabetes mellitus, 696 (21.94%) were found to have a history of diabetes and 2,477 (78.06%) were newly diagnosed. A lower prevalence was found in Zhuang ethnic minority people compared with the majority of Han people. The prevalence was significantly associated with age, body mass index, waist-to-hip ratio, dyslipidemia, medical history of hypertension, and family history of diabetes.
Guangxi shows a rapidly rising prevalence of diabetes. Weight control and blood lipid control are important to decrease the rapidly increasing prevalence of diabetes in Guangxi, an ethnic minority region.
PMCID: PMC4798220  PMID: 27042084
diabetes mellitus; ethnic minority; OGTT; diagnosis; factors; prevalence
12.  Growth of high quality and uniformity AlGaN/GaN heterostructures on Si substrates using a single AlGaN layer with low Al composition 
Scientific Reports  2016;6:23020.
By employing a single AlGaN layer with low Al composition, high quality and uniformity AlGaN/GaN heterostructures have been successfully grown on Si substrates by metal-organic chemical vapor deposition (MOCVD). The heterostructures exhibit a high electron mobility of 2150 cm2/Vs with an electron density of 9.3 × 1012 cm−2. The sheet resistance is 313 ± 4 Ω/◻ with ±1.3% variation. The high uniformity is attributed to the reduced wafer bow resulting from the balance of the compressive stress induced and consumed during the growth, and the thermal tensile stress induced during the cooling down process. By a combination of theoretical calculations and in situ wafer curvature measurements, we find that the compressive stress consumed by the dislocation relaxation (~1.2 GPa) is comparable to the value of the thermal tensile stress (~1.4 GPa) and we should pay more attention to it during growth of GaN on Si substrates. Our results demonstrate a promising approach to simplifying the growth processes of GaN-on-Si to reduce the wafer bow and lower the cost while maintaining high material quality.
PMCID: PMC4785338  PMID: 26960730
13.  Dynamic gene expression profiles during postnatal development of porcine subcutaneous adipose 
PeerJ  2016;4:e1768.
A better understanding of the control of lipogenesis is of critical importance for both human and animal physiology. This requires a better knowledge of the changes of gene expression during the process of adipose tissue development. Thus, the objective of the current study was to determine the effects of development on subcutaneous adipose tissue gene expression in growing and adult pigs. Here, we present a comprehensive investigation of mRNA transcriptomes in porcine subcutaneous adipose tissue across four developmental stages using digital gene expression profiling. We identified 3,274 differential expressed genes associated with oxidative stress, immune processes, apoptosis, energy metabolism, insulin stimulus, cell cycle, angiogenesis and translation. A set of universally abundant genes (ATP8, COX2, COX3, ND1, ND2, SCD and TUBA1B) was found across all four developmental stages. This set of genes may play important roles in lipogenesis and development. We also identified development-related gene expression patterns that are linked to the different adipose phenotypes. We showed that genes enriched in significantly up-regulated profiles were associated with phosphorylation and angiogenesis. In contrast, genes enriched in significantly down-regulated profiles were related to cell cycle and cytoskeleton organization, suggesting an important role for these biological processes in adipose growth and development. These results provide a resource for studying adipose development and promote the pig as a model organism for researching the development of human obesity, as well as being used in the pig industry.
PMCID: PMC4793310  PMID: 26989614
Pig; Subcutaneous adipose; Development; Gene expression
14.  The efficacy of iodine-125 permanent brachytherapy versus intensity-modulated radiation for inoperable salivary gland malignancies: study protocol of a randomised controlled trial 
BMC Cancer  2016;16:193.
Radiation therapy is the method of choice for subjects with inoperable salivary gland malignancies. I-125 brachytherapy, delivering a high radiation dose to a tumor but sparing surrounding normal tissues, is supposed to be ideal modality for the treatment of salivary gland malignancies. We designed a randomised controlled clinical trial to compare the efficacy of I-125 permanent brachytherapy (PBT) versus intensity-modulated radiation therapy (IMRT) for inoperable salivary gland malignancies.
In this study, inclusion criteria are subjects with inoperable salivary gland malignancies, aged 18–80 years, have provided informed consent, with at least one measurable tumor focus, be able to survive ≥3 months, Karnofsky performance status ≥60, have adequate hematopoietic function of bone marrow, have normal liver and kidney function, and are willing to prevent pregnancy.
Exclusion criteria include a history of radiation or chemotherapy, a history of other malignant tumors in the past 5 years, receiving other effective treatments, participating in other clinical trials, with circulatory metastasis, cognitive impairment, severe cardiovascular and cerebrovascular diseases, acute infection, uncontrolled systemic disease, history of interstitial lungdisease, and being pregnant or breast feeding.
The study will be conducted as a clinical, prospective, randomised controlled trial with balanced randomisation (1:1). The planned sample size is 90 subjects. Subjects with inoperable salivary gland malignancies are randomised to receive either I-125 PBT or IMRT, with stratification by tumor size and neck lymph node metastasis. Participants in both groups will be followed up at 2, 4, 6, 9, 12, 15, 18, 21 and 24 months after randomization. The primary outcome is local control rate of the primary site (based on imaging findings and clinical examination, RECIST criteria) in 1 year. Secondary outcomes are progression-free survival, overall survival, quality of life (QOL) measured with the European Organization for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30 and QLQ-H&N35) of Chinese version, and safety of treatment. Chi-squared test is used to compare the local control rates in both groups. The survival curves are estimated by the Kaplan-Meier method, and log-rank test is used to test the significant difference.
Only few observational studies have investigated the effect of I-125 PBT on inoperable salivary gland malignancies. To our knowledge, this is the first randomised controlled trial to investigate the efficacy of I-125 PBT for subjects with inoperable salivary gland malignancies, and will add to the knowledge base for the treatment of these subjects.
Trial registration
The study is registered to Clinical (NCT02048254) on Jan 29, 2014.
PMCID: PMC4782516  PMID: 26951097
I-125 permanent brachytherapy; Intensity-modulated radiation therapy; Inoperable salivary gland malignancy; Local control rate; Quality of life
15.  Steroidal Saponins from the Rhizomes of Aspidistra typica 
PLoS ONE  2016;11(3):e0150595.
Eleven new furostanol saponins, typaspidosides B-L (1–11), one new spirostanol saponin, typaspidoside M (12), and five known spirostanol saponins, 25S-atropuroside (13), neoaspidistrin (14), (25S)-pratioside D1 (15), 25S-aspidistrin (16) and 25S-neosibiricoside (17) were isolated from the rhizomes of Aspidistra typica Baill. The structures of the new compounds were established using 1D and 2D NMR (1H-1H COSY, HMQC, HMBC and ROESY) spectroscopy, high resolution mass spectrometry, and chemical methods. The aglycones of 1–3 (unusual furostanol saponins with opened E ring type), 9 and 10 (the methoxyl substituent at C-23 position) were found, identified from natural products for the first time. Moreover, the anti-HIV activities of the isolated steroidal glycosides were assessed, and compounds 13, 14, 16 and 17 exhibited high active against HIV-1.
PMCID: PMC4777403  PMID: 26937954
16.  A Retrospective Study on the Significance of Liver Biopsy and Hepatitis B Surface Antigen in Chronic Hepatitis B Infection 
Medicine  2016;95(8):e2503.
Supplemental Digital Content is available in the text
To investigate changes in the HBV replication level along with the natural course of chronic HBV infection and to examine the accuracy of the immune tolerant phase defined by the serological profile.
A total of 390 chronic HBV-infected patients were retrospectively recruited for this study. They were classified into immune-tolerance (IT), immune-clearance (IC), low-replicative (LR), and HBeAg-negative hepatitis (ENH) phases according to serological profiles (single-standard, SS) or dual-standard (DS) with the inclusion of liver histology. Serum HBV DNA and HBsAg were quantitatively measured, and liver histology was quantitatively analyzed.
The accuracy of the SS-defined IT phase was low, and active pathological changes were detected in 56 of 112 SS-defined IT patients. DS-defined IT patients had higher HBsAg levels (P = 0.0002) than the SS-defined patients. The quantitative HBsAg level can help identify SS-defined IT patients with potential liver injury. The area under the received operating characteristic curve for predicting the DS-defined IT phase was 0.831 (HBsAg 4.398 log IU/mL; sensitivity 87.5%; specificity 73.2%). HBV DNA was reduced by 4 logs, whereas HBsAg was only decreased by 2 logs with HBeAg positive to negative phase conversion.
Approximately half of IT patients defined by SS may have medium or severe liver injury. Quantitative measurement of the HBsAg level can help identify SS-defined IT patients with potential liver injury.
PMCID: PMC4778991  PMID: 26937895
17.  Amygdala NRG1–ErbB4 Is Critical for the Modulation of Anxiety-Like Behaviors 
Neuropsychopharmacology  2014;40(4):974-986.
Anxiety disorder is related to the pathophysiology of psychiatric diseases, including major depression, substance abuse, and schizophrenia. The amygdala is important for manifestation and modulation of anxiety. However, relatively little is known regarding the mechanisms that control the amygdala inhibitory activity that is involved in anxiety. We found that almost all ErbB4, which is the only autonomous receptor of neuregulin 1 (NRG1) in the basolateral amygdala (BLA), was expressed in GABAergic neurons. Endogenous NRG1–ErbB4 signaling pathway in the BLA could modulate anxiety-like behaviors and GABA release, whereas it had no effect on glutamatergic transmission. The administration of NRG1 into the BLA of high-anxiety mice alleviated their anxiety and enhanced GABAergic neurotransmission. Moreover, exogenous NRG1 also produced an anxiolytic effect in the stressed mice. Together, these observations indicated that NRG1–ErbB4 signaling is critical to maintaining GABAergic activity in the amygdala and thus to modulating anxiety-like behaviors. Because NRG1 and ErbB4 are susceptibility genes of schizophrenia, our findings might also help to explain the potential mechanism of emotional abnormality in schizophrenia.
PMCID: PMC4330511  PMID: 25308353
18.  Peroxisome proliferator-activated receptor γ inhibits pulmonary hypertension targeting store-operated calcium entry 
In this study, we investigated the role of peroxisome proliferator-activated receptor γ (PPARγ) on store-operated calcium entry (SOCE) and expression of the main store-operated calcium channels (SOCCs) components, canonical transient receptor potential (TRPC) in chronic hypoxia (CH) and monocrotaline (MCT)-induced PH rat models. siRNA knockdown and adenoviral overexpression strategies were constructed for both loss-of-function and gain-of-function experiments. PPARγ agonist rosiglitazone attenuates the pathogenesis of both CHPH and MCT-PH, suppresses Hif-1α, TRPC1, TRPC6 expression in the distal pulmonary artery (PA) and SOCE in freshly isolated rat distal pulmonary arterial smooth muscle cells (PASMCs). By comprehensive use of knockdown and overexpression studies, bioinformatically analysis of the TRPC gene promoter and luciferase reporter assay, we demonstrated that PPARγ exerts roles of anti-proliferation, anti-migration, and pro-apoptosis in PASMCs, likely by inhibiting the elevated SOCE and TRPC expression. These effects were inhibited under the conditions of hypoxia or Hif-1α accumulation. We also found that under hypoxia, accumulated Hif-1α protein acts as upstream of suppressed PPARγ level, however, targeted PPARγ rescue acts negative feedback on suppressing Hif-1α level and Hif-1α mediated signaling pathway. PPARγ inhibits PH by targeting SOCE and TRPC via inhibiting Hif-1α expression and signaling transduction.
PMCID: PMC4334731  PMID: 25391250
pulmonary hypertension; PPARγ; TRPC; Hif-1α
19.  Probabilistic map of language regions: challenge and implication 
Brain  2014;138(3):e337.
PMCID: PMC4408421  PMID: 25190682
20.  LSD1n is a H4K20 demethylase regulating memory formation via transcriptional elongation control 
Nature neuroscience  2015;18(9):1256-1264.
We report that a neuron-specific isoform of LSD1, LSD1n, resulting from an alternative splicing event, acquires a novel substrate specificity targeting histone H4 K20 methylation, both in vitro and in vivo. Selective genetic ablation of LSD1n leads to deficits in spatial learning and memory, revealing the functional importance of LSD1n in the regulation of neuronal activity-regulated transcription in a fashion indispensable for long-term memory formation. LSD1n occupies neuronal gene enhancers, promoters and transcribed coding regions, and is required for transcription initiation and elongation steps in response to neuronal activity, indicating the crucial role of H4K20 methylation in coordinating gene transcription with neuronal function. This study reveals that the alternative splicing of LSD1 in neurons, associated with altered substrate specificity, serves as an underlying mechanism acquired by neurons to achieve more precise control of gene expression in the complex processes underlying learning and memory.
PMCID: PMC4625987  PMID: 26214369
21.  Fabrication of Gelatin/PCL Electrospun Fiber Mat with Bone Powder and the Study of Its Biocompatibility 
Fabricating ideal scaffolds for bone tissue engineering is a great challenge to researchers. To better mimic the mineral component and the microstructure of natural bone, several kinds of materials were adopted in our study, namely gelatin, polycaprolactone (PCL), nanohydroxyapatite (nHA), and bone powder. Three types of scaffolds were fabricated using electrospinning; gelatin/PCL, gelatin/PCL/nHA, and gelatin/PCL/bone powder. Scaffolds were examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations. Then, Adipose-derived Stem Cells (ADSCs) were seeded on these scaffolds to study cell morphology, cell viability, and proliferation. Through this study, we found that nHA and bone powder can be successfully united in gelatin/PCL fibers. When compared with gelatin/PCL and gelatin/PCL/nHA, the gelatin/PCL/bone powder scaffolds could provide a better environment to increase ADSCs’ growth, adhesion, and proliferation. Thus, we think that gelatin/PCL/bone powder has good biocompatibility, and, when compared with nHA, bone powder may be more effective in bone tissue engineering due to the bioactive factors contained in it.
PMCID: PMC4810065  PMID: 26959071
gelatin; polycaprolactone; electrospinning; bone tissue engineering; scaffold
22.  Overexpression of RBM5 induces autophagy in human lung adenocarcinoma cells 
Dysfunctions in autophagy and apoptosis are closely interacted and play an important role in cancer development. RNA binding motif 5 (RBM5) is a tumor suppressor gene, which inhibits tumor cells’ growth and enhances chemosensitivity through inducing apoptosis in our previous studies. In this study, we investigated the relationship between RBM5 overexpression and autophagy in human lung adenocarcinoma cells.
Human lung adenocarcinoma cancer (A549) cells were cultured in vitro and were transiently transfected with a RBM5 expressing plasmid (GV287-RBM5) or plasmid with scrambled control sequence. RBM5 expression was determined by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Intracellular LC-3 I/II, Beclin-1, lysosome associated membrane protein-1 (LAMP1), Bcl-2, and NF-κB/p65 protein levels were detected by Western blot. Chemical staining with monodansylcadaverine (MDC) and acridine orange (AO) was applied to detect acidic vesicular organelles (AVOs). The ultrastructure changes were observed under transmission electron microscope (TEM). Then, transplanted tumor models of A549 cells on BALB/c nude mice were established and treated with the recombinant plasmids carried by attenuated Salmonella to induce RBM5 overexpression in tumor tissues. RBM5, LC-3, LAMP1, and Beclin1 expression was determined by immunohistochemistry staining in plasmids-treated A549 xenografts.
Our study demonstrated that overexpression of RBM5 caused an increase in the autophagy-related proteins including LC3-I, LC3-II, LC3-II/LC3-I ratio, Beclin1, and LAMP1 in A549 cells. A large number of autophagosomes with double-membrane structure and AVOs were detected in the cytoplasm of A549 cells transfected with GV287-RBM5 at 24 h. We observed that the protein level of NF-κB/P65 was increased and the protein level of Bcl-2 decreased by RBM5 overexpression. Furthermore, treatment with an autophagy inhibitor, 3-MA, enhanced RBM5-induced cell death and chemosensitivity in A549 cells. Furthermore, we successfully established the lung adenocarcinoma animal model using A549 cells. Overexpression of RBM5 enhanced the LC-3, LAMP1, and Beclin1 expression in the A549 xenografts.
Our findings showed for the first time that RBM5 overexpression induced autophagy in human lung adenocarcinoma cells, which might be driven by upregulation of Beclin1, NF-κB/P65, and downregulation of Bcl-2. RBM5-enhanced autophagy acts in a cytoprotective way and inhibition of autophagy may improve the anti-tumor efficacy of RBM5 in lung cancer.
PMCID: PMC4770605  PMID: 26923134
RNA binding motif 5; Autophagy; Non-small cell lung cancer; A549 xenograft; Gene expression
23.  Association of Hyperlipidemia, Inflammation and Serologic Status and Coronary Heart Disease among Patients with Rheumatoid Arthritis: Data from the National Veterans Health Administration 
Annals of the rheumatic diseases  2015;75(2):341-347.
To examine the association of serum lipids, inflammation and seropositivity on coronary heart disease (CHD) and stroke in rheumatoid arthritis (RA) patients.
The incidence of hospitalized myocardial infarction (MI) or stroke were calculated in a cohort of RA patients receiving care within the national Veterans Health Administration (VHA) from 1998–2011. Cox proportional hazard models were used to examine the association between these outcomes and low (LDL) cholesterol (C), high (HDL) density lipoprotein-C, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) as time-varying variables, divided into quintiles.
There were 37,568 RA patients in the cohort with mean age of 63 years (12.1 SD), 90% men. There was a no clear association between LDL-C and CHD/stroke. Compared to lower HDL-C (<34mg/dL), higher HDL-C (≥54 mg/dL) was inversely associated with MI (hazard ratio [HR] = 0.68, 95% CI 0.55, 0.85) and stroke HR = 0.69 (95% CI 0.50, 0.96). Higher CRP > 2.17 mg/dL (vs. CRP < 0.26 mg/dL) was associated with increased risk (HR= 2.43, =95% CI 1.77, 3.33) for MI and 2.02 (95% CI 1.32, 3.08) for stroke. ESR > 47 mm/hr compared to <8 mm/hr had a HR 1.87 (95% CI 1.39, 2.52) for MI and 2.00 (95% CI 1.26, 3.18) for stroke. The association between MI was significant for RA seroposotivity (HR=1.23, 95% CI 1.03, 1.48)
In this predominantly older male RA cohort, there was no clear association between LDL-C and CHD while higher HDL-C was inversely associated with MI and stroke. CRP and ESR were similarly associated with increase MI risk and stroke, reflecting the prominent role of inflammation in CHD risk in RA.
PMCID: PMC4752663  PMID: 25609412
rheumatoid arthritis; cardiovascular disease; C-reactive protein; cholesterol; lipoprotein; cardiovascular
24.  Expression of S100B during the innate immune of corneal epithelium against fungi invasion 
To explore the expression of S100B in corneal epithelial cells under Aspergillus stimulation both in vivo and in vitro.
Immortalized human corneal epithelial cells (HCECs) were exposed to inactive Aspergillus fumigatus (A. fumigatus) conidia at 0, 4, 8, 12, 16, and 24h respectively. The corneas of Wistar rats were exposed to active A. fumigatus at 0, 12, 24, 48h and the normal rat corneas were used for normal control. The mRNA level of S100B was evaluated by real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). S100B protein expression in cornea epithelium was detected by immunohistochemical/immunocytochemical staining (IHC/ICC).
Histopathology revealed a significant inflammatory cell infiltration in fungal keratitis human and rat cornea. Corneal epithelial cells didn't express or rarely express S100B at baseline. A. fumigatus significantly induced S100B mRNA expression in cultured corneal epithelial cells in a time depended manner in vitro, the mRNA began to rise significantly at 8h in vitro (P<0.05) and continue to rise as time prolonged (P<0.01). In vivo, S100B mRNA level was low in the normal corneas. However, it was increased in keratitis corneas from 12h after infection (P<0.05) and reached to a peak at 24h (P<0.001). Immunochemistry revealed an obvious staining in fungal keratitis corneas as well as immortalized HCECs compared to the normal ones respectively, indicating an increased expression of S100B protein.
S100B exists in corneal epithelial cells and is over-expressed under A. fumigatus stimulation. S100B may play an important role in the innate immune response of the corneal epithelium during A. fumigatus infection.
PMCID: PMC4761726  PMID: 26949634
S100B; cornea; Aspergillus fumigates; innate immunity
25.  Association of hyperlipidaemia, inflammation and serological status and coronary heart disease among patients with rheumatoid arthritis: data from the National Veterans Health Administration 
Annals of the Rheumatic Diseases  2015;75(2):341-347.
To examine the association of serum lipids, inflammation and seropositivity on coronary heart disease (CHD) and stroke in patients with rheumatoid arthritis (RA).
The incidence of hospitalised myocardial infarction (MI) or stroke was calculated in a cohort of patients with RA receiving care within the national Veterans Health Administration from 1998 to 2011. Cox proportional hazard models were used to examine the association between these outcomes and low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as time-varying variables, divided into quintiles.
There were 37 568 patients with RA in the cohort with mean age of 63 years (SD 12.1); 90% were men. There was a no clear association between LDL-C and CHD/stroke. Compared with lower HDL-C (<34 mg/dL), higher HDL-C (≥54 mg/dL) was inversely associated with MI (hazard ratio (HR)=0.68, 95% CI 0.55 to 0.85) and stroke (HR=0.69, 95% CI 0.50 to 0.96). Higher CRP >2.17 mg/dL (vs CRP <0.26 mg/dL) was associated with increased risk (HR=2.43, 95% CI 1.77 to 3.33) for MI and 2.02 (95% CI 1.32 to 3.08) for stroke. ESR >47 mm/h compared with <8 mm/h had an HR 1.87 (95% CI 1.39 to 2.52) for MI and 2.00 (95% CI 1.26 to 3.18) for stroke. The association between MI was significant for RA seropositivity (HR=1.23, 95% CI 1.03 to 1.48).
In this predominantly older male RA cohort, there was no clear association between LDL-C and CHD, whereas higher HDL-C was inversely associated with MI and stroke. CRP and ESR were similarly associated with increase MI risk and stroke, reflecting the prominent role of inflammation in CHD risk in RA.
PMCID: PMC4752663  PMID: 25609412
Rheumatoid Arthritis; Cardiovascular Disease; Inflammation

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