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1.  HIV-, HCV-, and Co-Infections and Associated Risk Factors among Drug Users in Southwestern China: A Township-Level Ecological Study Incorporating Spatial Regression 
PLoS ONE  2014;9(3):e93157.
Background
The human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are major public health problems. Many studies have been performed to investigate the association between demographic and behavioral factors and HIV or HCV infection. However, some of the results of these studies have been in conflict.
Methodology/Principal Findings
The data of all entrants in the 11 national methadone clinics in the Yi Autonomous Prefecture from March 2004 to December 2012 were collected from the national database. Several spatial regression models were used to analyze specific community characteristics associated with the prevalence of HIV and HCV infection at the township level. The study enrolled 6,417 adult patients. The prevalence of HIV infection, HCV infection and co-infection was 25.4%, 30.9%, and 11.0%, respectively. Prevalence exhibited stark geographical variations in the area studied. The four regression models showed Yi ethnicity to be associated with both the prevalence of HIV and of HIV/HCV co-infection. The male drug users in some northwestern counties had greater odds of being infected with HIV than female drug users, but the opposite was observed in some eastern counties. The ‘being in drug rehabilitation variable was found to be positively associated with prevalence of HCV infection in some southern townships, however, it was found to be negatively associated with it in some northern townships.
Conclusions/Significance
The spatial modeling creates better representations of data such that public health interventions must focus on areas with high frequency of HIV/HCV to prevent further transmission of both HIV and HCV.
doi:10.1371/journal.pone.0093157
PMCID: PMC3970964  PMID: 24687006
2.  The geographic distribution patterns of HIV-, HCV- and co-infections among drug users in a national methadone maintenance treatment program in Southwest China 
BMC Infectious Diseases  2014;14:134.
Background
HIV-, HCV- and HIV/HCV co-infections among drug users have become a rapidly emerging global public health problem. In order to constrain the dual epidemics of HIV/AIDS and drug use, China has adopted a methadone maintenance treatment program (MMTP) since 2004. Studies of the geographic heterogeneity of HIV and HCV infections at a local scale are sparse, which has critical implications for future MMTP implementation and health policies covering both HIV and HCV prevention among drug users in China. This study aimed to characterize geographic patterns of HIV and HCV prevalence at the township level among drug users in a Yi Autonomous Prefecture, Southwest of China.
Methods
Data on demographic and clinical characteristics of all clients in the 11 MMTP clinics of the Yi Autonomous Prefecture from March 2004 to December 2012 were collected. A GIS-based geographic analysis involving geographic autocorrelation analysis and geographic scan statistics were employed to identify the geographic distribution pattern of HIV-, HCV- and co-infections among drug users.
Results
A total of 6690 MMTP clients was analyzed. The prevalence of HIV-, HCV- and co-infections were 25.2%, 30.8%, and 10.9% respectively. There were significant global and local geographic autocorrelations for HIV-, HCV-, and co-infection. The Moran’s I was 0.3015, 0.3449, and 0.3155, respectively (P < 0.0001). Both the geographic autocorrelation analysis and the geographic scan statistical analysis showed that HIV-, HCV-, and co-infections in the prefecture exhibited significant geographic clustering at the township level. The geographic distribution pattern of each infection group was different.
Conclusion
HIV-, HCV-, and co-infections among drug users in the Yi Autonomous Prefecture all exhibited substantial geographic heterogeneity at the township level. The geographic distribution patterns of the three groups were different. These findings imply that it may be necessary to inform or invent site-specific intervention strategies to better devote currently limited resource to combat these two viruses.
doi:10.1186/1471-2334-14-134
PMCID: PMC3975583  PMID: 24612875
HIV; HCV; Co-infection; Geographic distribution; Geographic autocorrelation analysis; Geographic scan statistic
3.  A Replication Study for the Association of rs726252 in PAPPA2 with Developmental Dysplasia of the Hip in Chinese Han Population 
BioMed Research International  2014;2014:979520.
Developmental dysplasia of the hip (DDH) is a common developmental hip disorder, which ranges from mild acetabulum malformation to irreducible hip dislocation. A previous study suggested a significant association of pregnancy-associated plasma protein-A2 (PAPPA2) with DDH susceptibility in Chinese Han population. But with the consideration of the sample size, the association was still debatable. To confirm the association of the reported single nucleotide polymorphism (SNP) in PAPPA2, rs726252 with DDH, we conducted a case-control study in a larger number of subjects. We genotyped rs726252 in 697 DDH subjects and 707 control subjects by TaqMan assay. The association between this SNP and DDH was evaluated statistically. No significant difference was found in any comparison of genotype distribution nor allele frequency between cases and controls. Our replication study indicated that the association between rs726252 and DDH in Chinese Han population was debatable. The association between PAPPA2 and DDH should be evaluated by additional studies.
doi:10.1155/2014/979520
PMCID: PMC3930137  PMID: 24672801
4.  Case Report: Osteochondral Avulsion Fracture of the Posteromedial Bundle of the PCL in Knee Hyperflexion 
Background
Injury of the PCL of the knee in adults usually results in rupture rather than avulsion fracture and avulsions usually occur at the tibial insertion.
Case Description
We report an avulsion of the PCL with a femoral origin in a 22-year-old man who was injured by hyperflexion of the knee and was treated with arthroscopy. There were two parts in the partial osteochondral avulsion fracture of the PCL posteromedial (PM) bundle. One part was fixed with polydioxanone suture through drill holes and the other was removed. The fracture healed after 3 months and the knee was stable. At 11 months postoperatively the patient had returned to full-time work without pain or restrictions. The Lysholm II knee score was 95 points. Physical examination showed a negative posterior drawer sign.
Literature Review
We identified four other reported cases of PCL femoral origin avulsion fractures in adults. The subjects were 20 to 25 years old in four of five reports, including our patient. Three of the five patients had involvement of only the lateral cortex of the medial femoral condyle whereas two other patients including our patient, had an osteochondral fracture. The mechanism of PCL avulsion seems to be similar to that of a PCL rupture.
Purposes and Clinical Relevance
The hyperflexion injury may result in injury of the PM bundle of the PCL. Our case and one other in the literature suggest such avulsions need not involve the entire PCL.
doi:10.1007/s11999-012-2632-9
PMCID: PMC3492605  PMID: 23054525
5.  Chromatin-bound NLS proteins recruit membrane vesicles and nucleoporins for nuclear envelope assembly via importin-α/β 
Cell Research  2012;22(11):1562-1575.
The mechanism for nuclear envelope (NE) assembly is not fully understood. Importin-β and the small GTPase Ran have been implicated in the spatial regulation of NE assembly process. Here we report that chromatin-bound NLS (nuclear localization sequence) proteins provide docking sites for the NE precursor membrane vesicles and nucleoporins via importin-α and -β during NE assembly in Xenopus egg extracts. We show that along with the fast recruitment of the abundant NLS proteins such as nucleoplasmin and histones to the demembranated sperm chromatin in the extracts, importin-α binds the chromatin NLS proteins rapidly. Meanwhile, importin-β binds cytoplasmic NE precursor membrane vesicles and nucleoporins. Through interacting with importin-α on the chromatin NLS proteins, importin-β targets the membrane vesicles and nucleoporins to the chromatin surface. Once encountering Ran-GTP on the chromatin generated by RCC1, importin-β preferentially binds Ran-GTP and releases the membrane vesicles and nucleoporins for NE assembly. NE assembly is disrupted by blocking the interaction between importin-α and NLS proteins with excess soluble NLS proteins or by depletion of importin-β from the extract. Our findings reveal a novel molecular mechanism for NE assembly in Xenopus egg extracts.
doi:10.1038/cr.2012.113
PMCID: PMC3494395  PMID: 22847741
nuclear assembly; nucleoplasmin; Ran GTPase; nuclear pore complex; importin
6.  Hypolipidemic effect of gypenosides in experimentally induced hypercholesterolemic rats 
Background
To investigate the anti-hyperlipidemic effect of gynosaponins (GPs) in hyperlipidemic rats induced by high lipid diet.
Methods
Animal model of hyperlipidemia was established by high-fat and high-cholesterol diet. Rats were randomly divided into 6 groups, except the normal and model groups, rats in GPs groups were daily administered intragastrically with GPs (50, 100, and 200 mg/kg), and rats in simvastatin group were daily administered intragastrically with simvastatin (10 mg/kg). It was measured that the contents of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) in the serum, TG and TC in the liver during this experiment, respectively. The left lobe of liver was observed by histopathological staining, and the immunohistochemical staining was used to observe the effects on the effect of GPs on liver functions.
Results
Compared with the model group, GPs groups could remarkably decrease the content of lipids, GSH-Px, SOD, CAT and MDA in the serum and TC and TG in the liver of the hyperlipidemic rats. The pathomorphological results of hepatic tissue showed that fatty degeneration and inflammatory reaction of GPs groups were lightened compared with the model group.
Conclusions
The results show that GPs has good effects on the treatment of hyperlipidemia induced by high lipid diet in rats. The possible anti-hyperlipidemia mechanism maybe those GPs can regulate the disorder of lipid metabolism as well as ameliorate hepatic function.
doi:10.1186/1476-511X-12-154
PMCID: PMC3874657  PMID: 24160562
Gynosaponins; Hyperlipidemia; Lipid metabolism
7.  Lumbar disc degeneration is linked to a carbohydrate sulfotransferase 3 variant 
The Journal of Clinical Investigation  2013;123(11):4909-4917.
Lumbar disc degeneration (LDD) is associated with both genetic and environmental factors and affects many people worldwide. A hallmark of LDD is loss of proteoglycan and water content in the nucleus pulposus of intervertebral discs. While some genetic determinants have been reported, the etiology of LDD is largely unknown. Here we report the findings from linkage and association studies on a total of 32,642 subjects consisting of 4,043 LDD cases and 28,599 control subjects. We identified carbohydrate sulfotransferase 3 (CHST3), an enzyme that catalyzes proteoglycan sulfation, as a susceptibility gene for LDD. The strongest genome-wide linkage peak encompassed CHST3 from a Southern Chinese family–based data set, while a genome-wide association was observed at rs4148941 in the gene in a meta-analysis using multiethnic population cohorts. rs4148941 lies within a potential microRNA-513a-5p (miR-513a-5p) binding site. Interaction between miR-513a-5p and mRNA transcribed from the susceptibility allele (A allele) of rs4148941 was enhanced in vitro compared with transcripts from other alleles. Additionally, expression of CHST3 mRNA was significantly reduced in the intervertebral disc cells of human subjects carrying the A allele of rs4148941. Together, our data provide new insights into the etiology of LDD, implicating an interplay between genetic risk factors and miRNA.
doi:10.1172/JCI69277
PMCID: PMC3809787  PMID: 24216480
8.  Integrated Solid/Nanoporous Copper/Oxide Hybrid Bulk Electrodes for High-performance Lithium-Ion Batteries 
Scientific Reports  2013;3:2878.
Nanoarchitectured electroactive materials can boost rates of Li insertion/extraction, showing genuine potential to increase power output of Li-ion batteries. However, electrodes assembled with low-dimensional nanostructured transition metal oxides by conventional approach suffer from dramatic reductions in energy capacities owing to sluggish ion and electron transport kinetics. Here we report that flexible bulk electrodes, made of three-dimensional bicontinuous nanoporous Cu/MnO2 hybrid and seamlessly integrated with Cu solid current collector, substantially optimizes Li storage behavior of the constituent MnO2. As a result of the unique integration of solid/nanoporous hybrid architecture that simultaneously enhances the electron transport of MnO2, facilitates fast ion diffusion and accommodates large volume changes on Li insertion/extraction of MnO2, the supported MnO2 exhibits a stable capacity of as high as ~1100 mA h g−1 for 1000 cycles, and ultrahigh charge/discharge rates. It makes the environmentally friendly and low-cost electrode as a promising anode for high-performance Li-ion battery applications.
doi:10.1038/srep02878
PMCID: PMC3791456  PMID: 24096928
9.  Genetic Polymorphism of NOS3 with Susceptibility to Deep Vein Thrombosis after Orthopedic Surgery: A Case-Control Study in Chinese Han Population 
PLoS ONE  2013;8(7):e70033.
Deep vein thrombosis is one of the common complications of orthopedic surgery. Studies indicated that genetic factors played a considerable role in the pathogenesis of deep vein thrombosis. Endothelial nitric oxide synthase which encoded by nitric oxide synthase 3 (NOS3), can generate nitric oxide in endothelial cells. As a predominant regulator for vascular homeostasis, nitric oxide might be involved in the pathogenesis of thrombosis. It had been proved that the NOS3 polymorphism (rs1799983) was associated with the development of cardiovascular diseases. Our objective was to evaluate the association between the NOS3 polymorphism (rs1799983) and deep vein thrombosis after orthopedic surgery in Chinese Han population. The polymorphism was genotyped in 224 subjects with deep vein thrombosis after orthopedic surgery and 580 controls. Allele and genotype frequencies were compared between subjects with deep vein thrombosis and control subjects. The allele and genotype frequencies of the NOS3 polymorphism (rs1799983) were significantly different between subjects with deep vein thrombosis and control subjects. There were also significant differences when the subjects were stratified by gender, surgery type and hypertension status. These findings suggested that the NOS3 polymorphism (rs1799983) was associated with susceptibility to the deep vein thrombosis after orthopedic surgery in Chinese Han population, and NOS3 might play a role in the development of deep vein thrombosis after orthopedic surgery.
doi:10.1371/journal.pone.0070033
PMCID: PMC3724670  PMID: 23922896
10.  Vitamin E forms inhibit IL-13/STAT6-induced eotaxin-3 secretion by upregulation of PAR4, an endogenous inhibitor of atypical PKC in human lung epithelial cells 
Eotaxin-3 (CCL-26), a potent chemokine for eosinophil recruitment and contributing significantly to the pathogenesis of asthma, is secreted by lung epithelial cells in response to T helper 2 cytokines including interleukin 13 (IL-13). Here we showed that vitamin E forms, but not their metabolites, differentially inhibited IL-13-stimulated generation of eotaxin-3 in human lung epithelial A549 cells. The relative inhibitory potency was γ-tocotrienol (γ-TE) (IC50 ~15 μM) > γ-tocopherol, δ-tocopherol (IC50 ~25-50 μM) > α-tocopherol. Consistent with suppression of eotaxin, γ-TE treatment impaired IL-13-induced phosphorylation of STAT6, the key transcription factor for activation of eotaxin expression, and consequently blocked IL-13 stimulated DNA-binding activity of STAT6. In search of the upstream target of γTE by using inhibitor and siRNA approaches, we discovered that the atypical protein kinase C (aPKC) signaling, instead of classical PKC, p38 MAPK, JNK or ERK, played a critical role in IL-13-stimulated eotaxin generation and STAT6 activation. While showing no obvious effect on aPKC expression or phosphorylation, γ-TE treatment resulted in increased expression of PAR4, an endogenous negative regulator of aPKCs. Importantly, γ-TE treatment led to enhanced formation of aPKC/PAR4 complex that is known to reduce aPKC activity via protein-protein crosstalk. Our study demonstrated that γ-TE inhibited IL-13/STAT6-activated eotaxin secretion via up-regulation of PAR4 expression and enhancement of aPKC-PAR-4 complex formation. These results support the notion that specific vitamin E forms may be useful anti-asthmatic agents.
doi:10.1016/j.jnutbio.2011.03.003
PMCID: PMC3201713  PMID: 21764283
tocopherol; tocotrienol; asthma; inflammation
11.  Increasing Prevalence of Type 2 Diabetes in Chinese Adults in Shanghai 
Diabetes Care  2012;35(5):1028-1030.
OBJECTIVE
Our objective was to determine the secular trend in prevalence of type 2 diabetes in Shanghai, China.
RESEARCH DESIGN AND METHODS
Two consecutive population-based surveys for type 2 diabetes were conducted in randomly selected adults aged 35–74 years in Shanghai in 2002–2003 (n = 12,329) and in 2009 (n = 7,423). Diagnosed type 2 diabetes was determined based on self-report, whereas those undiagnosed were identified by measured fasting and postload glucose according to 2009 American Diabetes Association criteria.
RESULTS
Age-standardized prevalence of diagnosed and undiagnosed type 2 diabetes increased from 5.1 and 4.6% in 2002–2003 to 7.4 and 5.2% in 2009. The prevalence of type 2 diabetes increased with age and was higher among men and in urban residents in both surveys (P < 0.001). Between the two surveys, the increase in the prevalence was more evident in the rural population (P < 0.001) and appeared more rapid in younger birth cohorts (P < 0.05).
CONCLUSIONS
Our results suggest that Shanghai has experienced an increasing burden of type 2 diabetes.
doi:10.2337/dc11-1212
PMCID: PMC3329854  PMID: 22432111
12.  Spatial-temporal variations of Schistosoma japonicum distribution after an integrated national control strategy: a cohort in a marshland area of China 
BMC Public Health  2013;13:297.
Background
Schistosomiasis transmission is typically focal. Understanding spatial variations of Schistosoma infections and their associated factors is important to help to invent site-specific intervention strategies.
Methods
A five-year longitudinal study was carried out prospectively in 12 natural villages, Guichi district of Anhui province. A GIS-based spatial analysis was conducted to identify geographic distribution patterns of schistosomiasis infections at the household scale.
Results
The results of the spatial autocorrelation analysis for 2005 showed that there were significant spatial clusters of human infections at the household level, and these results were in agreement with that of the spatial scan statistic. As prevalence of infections in humans decreased over the course of control, the spatial distribution of these infections became less heterogeneous.
Conclusions
The findings imply that it may be necessary to re-assess risk factors of S. japonicum transmission over the course of control and to adjust accordingly control measures in the communities.
doi:10.1186/1471-2458-13-297
PMCID: PMC3621803  PMID: 23556428
Schistosomiasis; Intervention; Geographical information system; Spatial-temporal distribution; Spatial autocorrelation analysis; Spatial scan statistic; Schistosoma japonicum
13.  Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22 
Evangelou, Evangelos | Valdes, Ana M. | Kerkhof, Hanneke J.M | Styrkarsdottir, Unnur | Zhu, YanYan | Meulenbelt, Ingrid | Lories, Rik J. | Karassa, Fotini B. | Tylzanowski, Przemko | Bos, Steffan D. | Akune, Toru | Arden, Nigel K. | Carr, Andrew | Chapman, Kay | Cupples, L. Adrienne | Dai, Jin | Deloukas, Panos | Doherty, Michael | Doherty, Sally | Engstrom, Gunnar | Gonzalez, Antonio | Halldorsson, Bjarni V. | Hammond, Christina L. | Hart, Deborah J. | Helgadottir, Hafdis | Hofman, Albert | Ikegawa, Shiro | Ingvarsson, Thorvaldur | Jiang, Qing | Jonsson, Helgi | Kaprio, Jaakko | Kawaguchi, Hiroshi | Kisand, Kalle | Kloppenburg, Margreet | Kujala, Urho M. | Lohmander, L. Stefan | Loughlin, John | Luyten, Frank P. | Mabuchi, Akihiko | McCaskie, Andrew | Nakajima, Masahiro | Nilsson, Peter M. | Nishida, Nao | Ollier, William E.R. | Panoutsopoulou, Kalliope | van de Putte, Tom | Ralston, Stuart H. | Rivadeneira, Fernado | Saarela, Janna | Schulte-Merker, Stefan | Slagboom, P. Eline | Sudo, Akihiro | Tamm, Agu | Tamm, Ann | Thorleifsson, Gudmar | Thorsteinsdottir, Unnur | Tsezou, Aspasia | Wallis, Gillian A. | Wilkinson, J. Mark | Yoshimura, Noriko | Zeggini, Eleftheria | Zhai, Guangju | Zhang, Feng | Jonsdottir, Ingileif | Uitterlinden, Andre G. | Felson, David T | van Meurs, Joyce B. | Stefansson, Kari | Ioannidis, John P.A. | Spector, Timothy D.
Annals of the rheumatic diseases  2010;70(2):349-355.
Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in the elderly. It is characterized by changes in joint structure including degeneration of the articular cartilage and its etiology is multifactorial with a strong postulated genetic component. We performed a meta-analysis of four genome-wide association (GWA) studies of 2,371 knee OA cases and 35,909 controls in Caucasian populations. Replication of the top hits was attempted with data from additional ten replication datasets. With a cumulative sample size of 6,709 cases and 44,439 controls, we identified one genome-wide significant locus on chromosome 7q22 for knee OA (rs4730250, p-value=9.2×10−9), thereby confirming its role as a susceptibility locus for OA. The associated signal is located within a large (500kb) linkage disequilibrium (LD) block that contains six genes; PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, beta), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like), and BCAP29 (the B-cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.
doi:10.1136/ard.2010.132787
PMCID: PMC3615180  PMID: 21068099
14.  Urinary levels of nickel and chromium associated with dental restoration by nickel–chromium based alloys 
This paper aims to investigate if the dental restoration of nickel–chromium based alloy (Ni–Cr) leads to the enhanced excretions of Ni and Cr in urine. Seven hundred and ninety-five patients in a dental hospital had single or multiple Ni–Cr alloy restoration recently and 198 controls were recruited to collect information on dental restoration by questionnaire and clinical examination. Urinary concentrations of Ni and Cr from each subject were measure by graphite furnace atomic absorption spectrometry. Compared to the control group, the urinary level of Ni was significantly higher in the patient group of <1 month of the restoration duration, among which higher Ni excretions were found in those with either a higher number of teeth replaced by dental alloys or a higher index of metal crown not covered with the porcelain. Urinary levels of Cr were significantly higher in the three patient groups of <1, 1 to <3 and 3 to <6 months, especially in those with a higher metal crown exposure index. Linear curve estimations showed better relationships between urinary Ni and Cr in patients within 6-month groups. Our data suggested significant increased excretions of urinary Ni and Cr after dental restoration. Potential short- and long-term effects of Ni–Cr alloy restoration need to be investigated.
doi:10.1038/ijos.2013.13
PMCID: PMC3632762  PMID: 23579466
dental restoration; nickel–chromium based alloys; population investigation; urinary chromium; urinary nickel
15.  Differentially Expressed miRNAs after GnRH Treatment and Their Potential Roles in FSH Regulation in Porcine Anterior Pituitary Cell 
PLoS ONE  2013;8(2):e57156.
Hypothalamic gonadotropin-releasing hormone (GnRH) is a major regulator of follicle-stimulating hormone (FSH) secretion in gonadotrope cell in the anterior pituitary gland. microRNAs (miRNAs) are small RNA molecules that control gene expression by imperfect binding to the 3′-untranslated region (3′-UTR) of mRNA at the post-transcriptional level. It has been proven that miRNAs play an important role in hormone response and/or regulation. However, little is known about miRNAs in the regulation of FSH secretion. In this study, primary anterior pituitary cells were treated with 100 nM GnRH. The supernatant of pituitary cell was collected for FSH determination by enzyme-linked immunosorbent assay (ELISA) at 3 hours and 6 hours post GnRH treatment respectively. Results revealed that GnRH significantly promoted FSH secretion at 3 h and 6 h post-treatment by 1.40-fold and 1.80-fold, respectively. FSHβ mRNA at 6 h post GnRH treatment significantly increased by 1.60-fold. At 6 hours, cells were collected for miRNA expression profile analysis using MiRCURY LNA Array and quantitative PCR (qPCR). Consequently, 21 up-regulated and 10 down-regulated miRNAs were identified, and qPCR verification of 10 randomly selected miRNAs showed a strong correlation with microarray results. Chromosome location analysis indicated that 8 miRNAs were mapped to chromosome 12 and 4 miRNAs to chromosome X. Target and pathway analysis showed that some miRNAs may be associated with GnRH regulation pathways. In addition, In-depth analysis indicated that 10 up-regulated and 3 down-regulated miRNAs probably target FSHβ mRNA 3′-UTR directly, including miR-361-3p, a highly conserved X-linked miRNA. Most importantly, functional experimental results showed that miR-361-3p was involved in FSH secretion regulation, and up-regulated miR-361-3p expression inhibited FSH secretion, while down-regulated miR-361-3p expression promoted FSH secretion in pig pituitary cell model. These differentially expressed miRNAs resolved in this study provide the first guide for post-transcriptional regulation of pituitary gonadotrope FSH secretion in pig, as well as in other mammals.
doi:10.1371/journal.pone.0057156
PMCID: PMC3579806  PMID: 23451171
16.  Gamma-tocotrienol induces apoptosis and autophagy in prostate cancer cells by increasing intracellular dihydrosphingosine and dihydroceramide 
Although cell-based studies have shown that γ-tocotrienol (γTE) exhibits stronger anticancer activities than other forms of vitamin E including γ-tocopherol (γT), the molecular bases underlying γTE-exerted effects remains to be elucidated. Here we showed that γTE treatment promoted apoptosis, necrosis and autophagy in human prostate PC-3 and LNCaP cancer cells. In search of potential mechanisms of γTE-provoked effects, we found that γTE treatment led to marked increase of intracellular dihydroceramide and dihydrosphingosine, the sphingolipid intermediates in de novo sphingolipid synthesis pathway, but had no effects on ceramide or sphingosine. The elevation of these sphingolipids by γTE preceded or coincided with biochemical and morphological signs of cell death and was much more pronounced than that induced by γT, which accompanied with much higher cellular uptake of γTE than γT. The importance of sphingolipid accumulation in γTE-caused fatality was underscored by the observation that dihydrosphingosine and dihydroceramide potently reduced the viability of both prostate cell lines or LNCaP cells, respectively. In addition, myriosin, a specific inhibitor of de novo sphingolipid synthesis, counteracted γTE-induced cell death. In agreement with these cell-based studies, γTE inhibited LNCaP xenograft growth by 53% (P<0.05), compared with 33% (P = 0.07) by γT, in nude mice. These findings provide a molecular basis of γTE-stimulated cancer-cell death and support the notion that elevation of intracellular dihydroceramide and dihydrosphingosine is likely a novel anticancer mechanism.
doi:10.1002/ijc.26054
PMCID: PMC3381336  PMID: 21400505
sphingolipids; vitamin E; tocopherol; autophagy; apoptosis
17.  The Anorexigenic Effect of Serotonin Is Mediated by the Generation of NADPH Oxidase-Dependent ROS 
PLoS ONE  2013;8(1):e53142.
Serotonin (5-HT) is a central inhibitor of food intake in mammals. Thus far, the intracellular mechanisms for the effect of serotonin on appetite regulation remain unclear. It has been recently demonstrated that reactive oxygen species (ROS) in the hypothalamus are a crucial integrative target for the regulation of food intake. To investigate the role of ROS in the serotonin-induced anorexigenic effects, conscious mice were treated with 5-HT alone or combination with Trolox (a ROS scavenger) or Apocynin (an NADPH oxidase inhibitor) by acute intracerebroventricular injection. Both Trolox and Apocynin reversed the anorexigenic action of 5-HT and the 5-HT-induced hypothalamic ROS elevation. The mRNA and protein expression levels of pro-opiomelanocortin (POMC) were dramatically increased after ICV injection with 5-HT. The anorexigenic action of 5-HT was accompanied by markedly elevated hypothalamic MDA levels and GSH-Px activity, while the SOD activity was decreased. Moreover, 5-HT significantly increased the mRNA expression of UCP-2 but reduced the levels of UCP-3. Both Trolox and Apocynin could block the 5-HT-induced changes in UCP-2 and UCP-3 gene expression. Our study demonstrates for the first time that the anorexigenic effect of 5-HT is mediated by the generation of ROS in the hypothalamus through an NADPH oxidase-dependent pathway.
doi:10.1371/journal.pone.0053142
PMCID: PMC3541393  PMID: 23326391
18.  Factors impacting on progress towards elimination of transmission of schistosomiasis japonica in China 
Parasites & Vectors  2012;5:275.
Over the past decades China has made a great stride in controlling schistosomiasis, eliminating transmission of Schistosoma japonicum in 5 provinces and remarkably reducing transmission intensities in the rest of the seven endemic provinces. Recently, an integrated control strategy, which focuses on interventions on humans and bovines, has been implemented throughout endemic areas in China. This strategy assumes that a reduction in transmission of S. japonicum from humans and bovines to the intermediate Oncomelania snail host would eventually block the transmission of this parasite, and has yielded effective results in some endemic areas. Yet the transmission of S. japonicum is relatively complicated – in addition to humans and bovines, more than 40 species of mammalians can serve as potential zoonotic reservoirs. Here, we caution that some factors – potential roles of other mammalian reservoirs and human movement in sustaining the transmission, low sensitivity/specificity of current diagnostic tools for infections, praziquantel treatment failures, changes in environmental and socio-economic factors such as flooding in key endemic areas - may pose great obstacles towards transmission interruption of the parasite. Assessing potential roles of these factors in the transmission and implications for current control strategies aiming at transmission interruption is needed.
doi:10.1186/1756-3305-5-275
PMCID: PMC3519747  PMID: 23206326
Schistosoma japonicum; Integrated control strategy; Transmission interruption
19.  Novel functions of endocytic player clathrin in mitosis 
Cell Research  2011;21(12):1655-1661.
Clathrin has been widely recognized as a pivotal player in endocytosis, in which several adaptors and accessory proteins are involved. Recent studies suggested that clathrin is also essential for cell division. Here this review mainly focuses on the clathrin-dependent mechanisms involved in spindle assembly and chromosome alignment. In mitosis, clathrin forms a complex with phosphorylated TACC3 to ensure spindle stability and proper chromosome alignment. The clathrin-regulated mechanism in mitosis requires the crosstalk among clathrin, spindle assembly factors (SAFs), Ran-GTP and mitotic kinases. Meanwhile, a coordinated mechanism is required for role transitions of clathrin during endocytosis and mitosis. Taken together, the findings of the multiple functions of clathrin besides endocytosis have expanded our understanding of the basic cellular activities.
doi:10.1038/cr.2011.106
PMCID: PMC3357984  PMID: 21709692
clathrin; endocytosis; mitosis; TACC3; spindle assembly; chromosome alignment
20.  Influence of gonadotropin-releasing hormone agonist on the effect of chemotherapy upon ovarian cancer and the prevention of chemotherapy-induced ovarian damage: an experimental study with nu/nu athymic mice*  
Background and objective: Gonadotropin-releasing hormone (GnRH) plays an important role in the regulation of ovarian function and ovarian cancer cell growth. In this study, we determined whether administration of the GnRH agonist (GnRHa), triporelin, prior to cisplatin treatment affects cisplatin and/or prevents cisplatin-induced ovarian damage. Methods: nu/nu mice were injected with ovarian cancer OVCAR-3 cells intraperitoneally. After two weeks, the mice were treated with saline (control), cisplatin, GnRHa, or cisplatin plus GnRHa for four weeks. At the end of the experimental protocol, blood, tumor, ovary, and uterine tissues were resected for hematoxylin and eosin (H&E) staining, immunohistochemical analyses of Ki67, nuclear factor-κB (NF-κB), and caspase-3, transmission electron microscopy of apoptosis, or enzyme-linked immunosorbent assay (ELISA) analyses of anti-Mullerian hormone (AMH). Results: Cisplatin treatment effectively inhibited tumor growth in mice treated with human ovarian cancer cells; however the treatment also induced considerable toxicity. Immunohistochemical analyses showed that Ki67 expression was reduced in cisplatin-treated mice compared to control (P<0.05), but there was no statistically significant differences between cisplatin-treated mice and cisplatin plus GnRHa-treated mice (P>0.05), while expressions of NF-κB and caspase-3 were reduced and induced, respectively, in cisplatin-treated mice and cisplatin plus GnRHa-treated mice. Apoptosis occurred in the GnRHa, cisplatin, and cisplatin plus GnRHa-treated mice, but not in control mice. Ovaries exposed to GnRHa in both GnRHa mice and cisplatin-treated mice (combination group) had significantly more primordial and growth follicles and serum levels of AMH than those in the control mice and cisplatin-treated mice (P<0.05). Conclusions: Administration of GnRHa to mice significantly decreased the extent of ovarian damage induced by cisplatin, but did not affect the anti-tumor activity of cisplatin.
doi:10.1631/jzus.B1100369
PMCID: PMC3494028  PMID: 23125082
Gonadotrophin-releasing hormone; Cisplatin; Ovarian cancer; Animal experiment
21.  Association between bisphenol A exposure and body mass index in Chinese school children: a cross-sectional study 
Environmental Health  2012;11:79.
Background
There is increasing evidence suggesting that Bisphenol A (BPA), one of the highest volume chemicals produced worldwide, can interfere with the body’s natural weight control mechanisms to promote obesity. However, epidemiological studies for this are limited, especially for children.
Methods
A cross-sectional study was conducted to investigate the association between BPA exposure and body mass index (BMI) in school children. Three primary and three middle schools were randomly selected from 26 primary and 30 middle candidate schools in Changning District of Shanghai City in China. According to the BMI-based criteria by age and sex for screening of overweight or obese children, we randomly chose 20 obese, 10 overweight, and 30 normal weight children aged 8-15 years of age from each selected school. First morning urine was collected and total urine BPA concentrations were determined by ultra-performance liquid chromatography tandem mass spectrometry. Multiple linear regression analysis was conducted to examine the association of urine BPA concentrations and daily intake estimates with BMI.
Results
BPA was detected in 84.9% of urine samples with a geometric mean of 0.45 ng/mL. The daily intake estimates ranged from 0.03 μg/day to 1.96 μg/day with a geometric mean of 0.37 μg/day. The average urine BPA concentrations and daily intake estimates were similar for boys and girls, but significantly higher in older children than younger ones, and showed an increasing trend with BMI. Multiple linear regression analyses showed that urine BPA concentrations were significantly associated with increasing BMI values in all subjects after adjustment for age and sex and the results were similar before and after corrected by urine specific gravity. When stratified by age or sex, the associations remained significant in females and in those 8-11 years of age before corrected by specific gravity. Similar results were shown for the association between BMI and daily intake estimates.
Conclusions
There is a possibility that BPA exposure increases BMI in school children. Given the cross-sectional nature of this study, longitudinal studies are warranted to confirm BPA exposure as a contributor to increased BMI in children.
doi:10.1186/1476-069X-11-79
PMCID: PMC3549797  PMID: 23083070
Bisphenol A; Urine; Body mass index; Obesity; School children
22.  CD20-positive NK/T-cell lymphoma with indolent clinical course: report of case and review of literature 
Diagnostic Pathology  2012;7:133.
Abstract
CD20-positive T-cell lymphoma is extremely rare and only two cases of CD20-positive NK/T-cell lymphoma with aggressive clinical courses have been described in the literature. We present a case of unusual NK/T-cell lymphoma with CD20 expression in nasal cavity occurring in an elder female patient. The patient had presented with left nasal cavity nodule for 10 years. CT scan revealed a mass was located at the left anterior nasal cavity and was observed to extend into the ethmoid sinus. There was no regional lymph node involvement. Biopsy was performed and microscopical inspection revealed the lesion was composed of small- to middle-size atypical lymphoid cell, histiocytes, eosinophils, and neutrophils. The lymphoid cells were strongly immunoreactive to CD3, CD20, CD56, TIA-1 and granzyme-B. The Epstein-Barr virus genomes were also found in tumor cells by in situ hybridization. By genetic analysis, however, no clonal rearrangement of the T cell receptor-γ genes (TCRG), or the immunoglobulin heavy chain (IgH) gene was found. A diagnosis of CD20-positive extranodal NK/T-cell lymphoma, nasal type was made. The patient refused chemotherapy, and had been only on regular follow-up for 6 months. There was no sign of enlargement of tumor and extra-nasal dissemination by whole body positron emission tomography/computed tomography (PET/CT) study. The accurate diagnosis of NK/T-cell lymphoma with CD20 expression is important, but the indolent behavior of the present case is more unusual. A long-term follow-up is suggested to be performed to inspect the progression for this tumor.
Virtual slides
The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1320848277788495
doi:10.1186/1746-1596-7-133
PMCID: PMC3502398  PMID: 23031227
NK/T cell lymphoma; Nasal type; CD20 expression; Differential diagnosis; Prognosis
23.  Pd/C Synthesized with Citric Acid: An Efficient Catalyst for Hydrogen Generation from Formic Acid/Sodium Formate 
Scientific Reports  2012;2:598.
A highly efficient hydrogen generation from formic acid/sodium formate aqueous solution catalyzed by in situ synthesized Pd/C with citric acid has been successfully achieved at room temperature. Interestingly, the presence of citric acid during the formation and growth of the Pd nanoparticles on carbon can drastically enhance the catalytic property of the resulted Pd/C, on which the conversion and turnover frequency for decomposition of formic acid/sodium formate system can reach the highest values ever reported of 85% within 160 min and 64 mol H2 mol−1 catalyst h−1, respectively, at room temperature. The present simple, low cost, but highly efficient CO-free hydrogen generation system at room temperature is believed to greatly promote the practical application of formic acid system on fuel cells.
doi:10.1038/srep00598
PMCID: PMC3432491  PMID: 22953041
24.  Deformation-induced localized solid-state amorphization in nanocrystalline nickel 
Scientific Reports  2012;2:493.
Although amorphous structures have been widely obtained in various multi-component metallic alloys, amorphization in pure metals has seldom been observed and remains a long-standing scientific curiosity and technological interest. Here we present experimental evidence of localized solid-state amorphization in bulk nanocrystalline nickel introduced by quasi-static compression at room temperature. High-resolution electron microscope observations illustrate that nano-scale amorphous structures present at the regions where severe deformation occurred, e.g. along crack paths or surrounding nano-voids. These findings have indicated that nanocrystalline structures are highly desirable for promoting solid-state amorphization, which may provide new insights for understanding the nature of the crystalline-to-amorphous transformation and suggested a potential method to produce elemental metallic glasses that have hardly been available hitherto through rapid solidification.
doi:10.1038/srep00493
PMCID: PMC3389370  PMID: 22768383
25.  An Integrated Strategy for Transmission Control of Schistosoma japonicum in a Marshland Area of China: Findings from a Five-Year Longitudinal Survey and Mathematical Modeling 
In 2004 an aggressive plan was instituted aiming to achieve nationwide transmission control of schistosomiasis by 2015. Here, we report a longitudinal study on the control of schistosomiasis in Anhui province, China. Using a mathematical model, we compared the effects of different control strategies implemented in the study area. During the 5-year study period, a 60.8% reduction in human prevalence was observed from 2005 (7.95%) to 2009 (3.1%), and snail infection decreased from 0.063% in 2005 to zero in 2009. Results of the model agree well with the first 3-year field observations and suggest continuous decrease in human infections in the last 2 years, whereas the last 2-year field observations indicated that human infections appeared to be stable even with continuous control. Our findings showed that the integrated control strategy was effective, and we speculated that other factors besides bovines might contribute to the local transmission of the disease.
doi:10.4269/ajtmh.2011.10-0574
PMCID: PMC3122349  PMID: 21734130

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