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author:("Wang, lisun")
1.  Secondary Antifungal Prophylaxis in Hematological Malignancy Patients with Previous Invasive Fungal Disease: A Retrospective Analysis 
PLoS ONE  2014;9(12):e115461.
Background
Invasive fungal disease (IFD) causes morbidity and mortality in patients with hematological malignancy. Recurrence of IFD after chemotherapy or hematopoietic stem cell transplantation (HSCT) is associated with poor prognosis. The present study aimed to investigate the efficacy of different strategies of secondary antifungal prophylaxis (SAP) for IFD and choose an appropriate SAP regimen.
Methods
Clinical data of patients with previous IFD who underwent chemotherapy or HSCT between Jan 2008 and Jun 2013 were retrospectively reviewed and followed up to 180 days post-chemotherapy or HSCT. The clinical characteristics and diagnosis were analyzed according to the diagnostic criteria for IFD. The efficacy of different strategies for SAP and risk factors influencing the failure of SAP were evaluated.
Results
Of the 164 patients enrolled, 121 patients received SAP regimen (73.78%), and IFD recurred in 40 patients: 16.5% (20/121) in SAP group and 46.5% (20/43) in non-SAP group. In SAP group, 58 received SAP agents which were proven effective for their previous IFD, while other 63 patients received other broad-spectrum antifungal agents. There was no significant difference in the recurrence rates between these two subgroups (13.8% (8/58) vs 19.0% (12/63), P = 0.437). The IFD recurrence rates were statistically significant between patients with allogeneic HSCT and chemotherapy or autologous HSCT (25% vs 8.2%, P = 0.013). Multivariate analysis indicated that allogeneic HSCT was the independent risk factor of IFD recurrence after SAP.
Conclusions
Secondary antifungal prophylaxis is necessary to prevent IFD recurrence in patients with hematological malignancy, especially for patients in the setting of allogeneic HSCT.
doi:10.1371/journal.pone.0115461
PMCID: PMC4274009  PMID: 25531544
2.  Transcriptomic Analysis of Grape (Vitis vinifera L.) Leaves after Exposure to Ultraviolet C Irradiation 
PLoS ONE  2014;9(12):e113772.
Background
Only a small amount of solar ultraviolet C (UV-C) radiation reaches the Earth's surface. This is because of the filtering effects of the stratospheric ozone layer. Artificial UV-C irradiation is used on leaves and fruits to stimulate different biological processes in plants. Grapes are a major fruit crop and are grown in many parts of the world. Research has shown that UV-C irradiation induces the biosynthesis of phenols in grape leaves. However, few studies have analyzed the overall changes in gene expression in grape leaves exposed to UV-C.
Methodology/Principal Findings
In the present study, transcriptional responses were investigated in grape (Vitis vinifera L.) leaves before and after exposure to UV-C irradiation (6 W·m−2 for 10 min) using an Affymetrix Vitis vinifera (Grape) Genome Array (15,700 transcripts). A total of 5274 differentially expressed probe sets were defined, including 3564 (67.58%) probe sets that appeared at both 6 and 12 h after exposure to UV-C irradiation but not before exposure. A total of 468 (8.87%) probe sets and 1242 (23.55%) probe sets were specifically expressed at these times. The probe sets were associated with a large number of important traits and biological pathways, including cell rescue (i.e., antioxidant enzymes), protein fate (i.e., HSPs), primary and secondary metabolism, and transcription factors. Interestingly, some of the genes involved in secondary metabolism, such as stilbene synthase, responded intensely to irradiation. Some of the MYB and WRKY family transcription factors, such as VvMYBPA1, VvMYB14, VvMYB4, WRKY57-like, and WRKY 65, were also strongly up-regulated (about 100 to 200 fold).
Conclusions
UV-C irridiation has an important role in some biology processes, especially cell rescue, protein fate, secondary metabolism, and regulation of transcription.These results opened up ways of exploring the molecular mechanisms underlying the effects of UV-C irradiation on grape leaves and have great implications for further studies.
doi:10.1371/journal.pone.0113772
PMCID: PMC4252036  PMID: 25464056
3.  Application of propensity scores to explore the effect of public reporting of medicine use information on rational drug use in China: a quasi-experimental design 
Background
Transparency has become a hottest topic and a growing movement in the health care system worldwide. This study used a quasi-experimental design method to explore whether public reporting of medicine use information can improve rational drug use.
Methods
20 township hospitals and 274 doctors of City Y in Hubei Province, China were divided into the intervention and control groups on the basis of their characteristics. In the intervention group, the values and rankings of the average expenditure per prescription, percentage of prescriptions requiring antibiotics and percentage of prescriptions requiring injections of each hospital and doctor were publicly released to patients and doctors in an appropriate format monthly. Data were gathered both four months before and after the intervention. Propensity score matching (PSM) was used to minimize the observed covariate (gender, age, experience, education level, title, and monthly income) differences in the doctors’ characteristics. 108 pairs of doctors were obtained after PSM. Chi-square test and t-test were employed to explore the effect of public reporting of medicine use information on rational drug use. The study was approved by the Committee of Tongji Medical College, Hua Zhong University of Science and Technology (IORG No: IORG0003571).
Results
In baseline, the average expenditure per prescription of the 274 doctors was 42.82 RMB yuan (USD 6.97), the percentage of prescriptions requiring antibiotics was 63.00%, and the percentage of prescriptions requiring injections was 70.79%, all higher than the average of Hubei Province and the standard recommended by WHO. Before the intervention all the three indicators were all comparable (p > 0.05), whereas after the intervention, a significant difference (p < 0.05) was found for the percentage of prescriptions requiring injections between the intervention (64.66%) and control groups (70.52%).
Conclusions
Irrational drug use remains a policy issue in township hospitals in the study area. We demonstrated that publicly reporting medicine use information could decrease the percentage of prescriptions requiring injections in township hospitals in China, but this effect was not observed on prescription costs and antibiotics use. Analyses of the mechanism and long-term effect of public reporting of medicine use information are recommended for further studies.
doi:10.1186/s12913-014-0492-6
PMCID: PMC4232652  PMID: 25384897
Quasi-experimental design; Propensity score; Township hospitals; Transparency; Rational drug use; China
4.  Identifying the Core Components of Emotional Intelligence: Evidence from Amplitude of Low-Frequency Fluctuations during Resting State 
PLoS ONE  2014;9(10):e111435.
Emotional intelligence (EI) is a multi-faceted construct consisting of our ability to perceive, monitor, regulate and use emotions. Despite much attention being paid to the neural substrates of EI, little is known of the spontaneous brain activity associated with EI during resting state. We used resting-state fMRI to investigate the association between the amplitude of low-frequency fluctuations (ALFFs) and EI in a large sample of young, healthy adults. We found that EI was significantly associated with ALFFs in key nodes of two networks: the social emotional processing network (the fusiform gyrus, right superior orbital frontal gyrus, left inferior frontal gyrus and left inferior parietal lobule) and the cognitive control network (the bilateral pre-SMA, cerebellum and right precuneus). These findings suggest that the neural correlates of EI involve several brain regions in two crucial networks, which reflect the core components of EI: emotion perception and emotional control.
doi:10.1371/journal.pone.0111435
PMCID: PMC4214743  PMID: 25356830
5.  Split-Cre Complementation Restores Combination Activity on Transgene Excision in Hair Roots of Transgenic Tobacco 
PLoS ONE  2014;9(10):e110290.
The Cre/loxP system is increasingly exploited for genetic manipulation of DNA in vitro and in vivo. It was previously reported that inactive ‘‘split-Cre’’ fragments could restore Cre activity in transgenic mice when overlapping co-expression was controlled by two different promoters. In this study, we analyzed recombination activities of split-Cre proteins, and found that no recombinase activity was detected in the in vitro recombination reaction in which only the N-terminal domain (NCre) of split-Cre protein was expressed, whereas recombination activity was obtained when the C-terminal (CCre) or both NCre and CCre fragments were supplied. We have also determined the recombination efficiency of split-Cre proteins which were co-expressed in hair roots of transgenic tobacco. No Cre recombination event was observed in hair roots of transgenic tobacco when the NCre or CCre genes were expressed alone. In contrast, an efficient recombination event was found in transgenic hairy roots co-expressing both inactive split-Cre genes. Moreover, the restored recombination efficiency of split-Cre proteins fused with the nuclear localization sequence (NLS) was higher than that of intact Cre in transgenic lines. Thus, DNA recombination mediated by split-Cre proteins provides an alternative method for spatial and temporal regulation of gene expression in transgenic plants.
doi:10.1371/journal.pone.0110290
PMCID: PMC4201524  PMID: 25329460
6.  Premelanosome-negative inflammatory angiomyolipoma of liver with expression of cathepsin K and TFE3 
We report the first case of inflammatory variant of hepatic angiomyolipoma (AML) with expression of transcription factor E3 (TFE3) protein but negativity for HMB45 and melan A in a 62-year-old female. Imaging studies revealed a tumor in the left lobe of liver, sized 5.8 cm in maximum diameter. Microscopically, the lesion was composed of large polygonal or epithelioid cells with copious eosinophilic granular cytoplasm. There was a very prominent stromal lymphoplasmacytic infiltrate. Immunohistochemically, the tumor cells showed very strong and diffuse positivity for smooth muscle actin, and cathepsin K, while S-100 protein, keratin, desmin, HMB45 and Melan-A are negative. However, there was multifocal and very convincing nuclear positivity for TFE3, thus confirms the diagnosis.
PMCID: PMC4270569  PMID: 25550868
Liver; angiomyolipoma; inflammatory; epithelioid tumor; TFE3; cathepsin K; differential diagnosis
7.  Public reporting improves antibiotic prescribing for upper respiratory tract infections in primary care: a matched-pair cluster-randomized trial in China 
Background
Inappropriate use and overuse of antibiotics is a serious concern in the treatment of upper respiratory tract infections (URTIs), especially in developing countries. In recent decades, information disclosure and public reporting (PR) has become an instrument for encouraging good practice in healthcare. This study evaluated the impact of PR on antibiotic prescribing for URTIs in a sample of primary care institutions in China.
Methods
A matched-pair cluster-randomized trial was undertaken in QJ city, with 20 primary care institutions participating in the trial. Participating institutions were matched into pairs before being randomly assigned into a control and an intervention group. Prescription statistics were disclosed to patients, health authorities, and health workers monthly within the intervention group, starting from October 2013. Outpatient prescriptions for URTIs were collected from both groups before (1st March to 31st May, 2013) and after the intervention (1st March to 31st May, 2014). A total of 34,815 URTI prescriptions were included in a difference-in-difference analysis using multivariate linear or logistic regression models, controlling for patient attributes as well as institutional characteristics.
Results
Overall, 90% URTI prescriptions required antibiotics and 21% required combined use of antibiotics. More than 77% of URTI prescriptions required intravenous (IV) injection or infusion of drugs. PR resulted in a 9 percentage point (95% CI -17 to -1) reduction in the use of oral antibiotics (adjusted RR =39%, P =0.027), while the use of injectable antibiotics remained unchanged. PR led to a 7 percentage point reduction (95% CI -14 to 0; adjusted RR =36%) in combined use of antibiotics (P =0.049), which was largely driven by a significant reduction in male patients (-7.5%, 95% CI -14 to -1, P =0.03). The intervention had little impact on the use of IV injections or infusions, or the total prescription expenditure.
Conclusions
The results suggest that PR could improve prescribing practices in terms of reducing oral antibiotics and combined use of antibiotics; however, the impacts were limited. We suggest that PR would probably be enhanced by provider payment reform, management and training for providers, and health education for patients.
doi:10.1186/1478-4505-12-61
PMCID: PMC4197333  PMID: 25304996
Antibiotics; China; Primary care; Public reporting; Upper respiratory tract infection
8.  Association between carcinoembryonic antigen levels and the applied value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in post-operative recurrent and metastatic colorectal cancer 
Oncology Letters  2014;8(6):2649-2653.
Positron emission tomography (PET) using 18F-fluorodeoxyglucose has been widely used for analyzing cellular metabolism. The present study aimed to evaluate the association between the diagnostic value of PET/computed tomography (CT) in patients with post-operative recurrent and metastatic colorectal cancer (CRC), and the different levels of carcinoembryonic antigen (CEA). A total of 105 suspected recurrent and metastatic CRC patients (67 males and 38 females; mean age, 48.5 years) were included in this retrospective study. All the patients underwent PET/CT examination. The differences in the PET/CT diagnostic values of CEA-positive and -negative patients with recurrent CRC following surgery were retrospectively analyzed and compared. Among the 105 CRC patients, 87 exhibited recurrence and metastasis, as confirmed by histopathological diagnosis or clinical follow-up data. By contrast, the PET/CT examination results revealed that 85 cases were true positives (a false positive foci was diagnosed in one of the patients), 18 were true negatives and 2 were false negatives. Correspondingly, the sensitivity and degree of accuracy were 97.7 and 97.1%, respectively. The detection rates of PET/CT for the recurrence and metastases were 85.3% in the CEA-positive group and 75.7% in the CEA-negative group. No significant differences were observed between the two groups. Overall, CEA levels do not help improve the detection rate of PET/CT in the recurrence and metastasis of CRC. PET/CT imaging has a high sensitivity and degree of accuracy in detecting recurrence and metastasis following CRC surgery. Therefore, this method is ideal for monitoring relapsed and metastatic foci of post-operative colon cancer cases.
doi:10.3892/ol.2014.2523
PMCID: PMC4214442  PMID: 25364443
colorectal neoplasm; positron emission tomography; carcinoembryonic antigen
9.  A Novel Wide-Area Backup Protection Based on Fault Component Current Distribution and Improved Evidence Theory 
The Scientific World Journal  2014;2014:493739.
In order to solve the problems of the existing wide-area backup protection (WABP) algorithms, the paper proposes a novel WABP algorithm based on the distribution characteristics of fault component current and improved Dempster/Shafer (D-S) evidence theory. When a fault occurs, slave substations transmit to master station the amplitudes of fault component currents of transmission lines which are the closest to fault element. Then master substation identifies suspicious faulty lines according to the distribution characteristics of fault component current. After that, the master substation will identify the actual faulty line with improved D-S evidence theory based on the action states of traditional protections and direction components of these suspicious faulty lines. The simulation examples based on IEEE 10-generator-39-bus system show that the proposed WABP algorithm has an excellent performance. The algorithm has low requirement of sampling synchronization, small wide-area communication flow, and high fault tolerance.
doi:10.1155/2014/493739
PMCID: PMC4090531  PMID: 25050399
10.  Comparison of investigation methods of heat injury in grapevine (Vitis) and assessment to heat tolerance in different cultivars and species 
BMC Plant Biology  2014;14:156.
Background
In the context of global climate change, heat stress is becoming an increasingly important constraint on grapevine growth and berry quality. There is a need to breed new grape cultivars with heat tolerance and to design effective physiological defenses against heat stress. The investigation of heat injury to plants or tissues under high temperature is an important step in achieving these goals. At present, evaluation methods for heat injury include the gas exchange parameters of photosynthesis, membrane thermostability, chlorophyll content etc.; however, these methods have obvious disadvantages, such as insensitivity, inconvenience and delayed information. An effective and convenient method for investigating the heat injury of grapevine must be developed.
Results
In this study, an investigation protocol for a critical temperature (47°C) and heat treatment time (40 min) was developed in detached grape leaves. Based on the results, we found that the OJIP test was superior to measuring electrolyte leakage or photosynthetic O2 evolution for investigating the heat injury of three cultivars of grapevine. Heat tolerance of 47 grape species and cultivars was evaluated through investigating heat injury using the OJIP test. Moreover, the electron transport chain (donor side, acceptor side and reaction center) of PSII in photosynthesis was further investigated.
Conclusions
The OJIP test was a rapid, sensitive and convenient method for investigating heat injury in grapevine. An analysis of PSII function using this method indicated that the acceptor side was less sensitive to heat than was the donor side or the reaction center in grape leaves. Among the 47 taxa evaluated (cultivars, hybrids, and wild species), heat tolerance varied largely in each genotype group: most wild species and hybrids between V. labrusca and V. vinifera had relatively strong heat tolerance, but most cultivars from V. vinifera had relatively weak heat tolerance.
doi:10.1186/1471-2229-14-156
PMCID: PMC4099030  PMID: 24898786
11.  Angiotensin II (AngII) stimulates basolateral 10 pS Cl channels in the thick ascending limb 
Hypertension  2013;61(6):1211-1217.
Cl channels in the basolateral membrane play a key role in Cl absorption in the thick ascending limb (TAL). The patch clamp experiments were performed to test whether AngII increases Cl absorption in the TAL by stimulating the basolateral 10 pS Cl channels. AngII (1-100 nM) stimulated the 10 pS Cl channel in the TAL, an effect that was blocked by losartan (AT1R antagonist) but not by PD123319 (AT2R antagonist). Inhibition of phospholipase C (PLC) or protein kinase C (PKC) also abolished the stimulatory effect of AngII on Cl channels. Moreover, stimulation of PKC with phorbol 12-myristate 13-acetate (PMA) mimicked the effect of AngII and increased Cl channel activity. However, the stimulatory effect of AngII on Cl channels was absent in the TAL pretreated with DPI, an inhibitor of NADPH-dependent oxidase (NOX). Moreover, treatment of the TAL with DPI also blocked the effect of PMA on the 10 pS Cl channel. Western blotting demonstrated that incubation of isolated TAL with AngII increased phosphorylation of P47phox at Ser304, suggesting that AngII stimulates the basolateral Cl channels by increasing NOX-dependent superoxide generation. This notion was also supported by the observation that H2O2 significantly increased 10 pS Cl channel activity in the TAL. We conclude that stimulation of AT1R increased the basolateral Cl channels by activating the PKC-dependent NOX pathway. The stimulatory effect of AngII on the basolateral Cl channel may contribute to AngII-induced increases in NaCl reabsorption in the TAL and AngII-infuse-induced hypertension.
doi:10.1161/HYPERTENSIONAHA.111.01069
PMCID: PMC3686115  PMID: 23569086
Angiotensin II receptor; PKC; NADPH oxidase; ClC-kb; hypertension
12.  Hepatocellular carcinoma metastasis to the lacrimal gland: A case report 
Oncology Letters  2014;8(2):911-913.
Hepatocellular carcinoma (HCC) is a globally common neoplasm, with regional metastasis associated with >50% of the tumors. Extrahepatic metastasis is also common, with the lungs, diaphragm, abdominal lymph nodes and bone being the most frequently affected regions. However, to the best of our knowledge, HCC metastasis to the lacrimal gland has not been reported in the literature. Only one case of metastasis to the lacrimal sac from a renal cell carcinoma has been reported. The current study presents the case of a 56-year-old male with ocular symptoms who was eventually diagnosed with HCC. The therapeutic alternatives for such cases are also discussed according to the reviewed literature. Clinicians should be watchful for the appearance of tumors in the lacrimal gland in patients with a history of malignancy.
doi:10.3892/ol.2014.2191
PMCID: PMC4081277  PMID: 25013516
hepatocellular carcinoma; metastasis; lacrimal gland
13.  Toxicity, uptake kinetics and behavior assessment in zebrafish embryos following exposure to perfluorooctanesulphonicacid (PFOS) 
Perfluorooctanesulphonicacid (PFOS), a persistent organic contaminant, has been widely detected in the environment, wildlife and humans, but few studies have assessed its effect on aquatic organisms. The present study evaluated the effect of PFOS on zebrafish embryos. Zebrafish embryos exhibited bent spine and developmental toxicity after exposure to various PFOS concentrations (0.01-16.0 μM) from 6 to 120 hour post-fertilization (hpf). The LC50 at 120 hpf was 4.39 μM and the EC50 at 120 hpf was 2.23 μM. PFOS induced apoptosis at 24 hpf was consistently located in the brain, eye, and tail region of embryos. PFOS elevated the basal rate of swimming after 4 days of exposure, and larvae exposed to PFOS (0.5-8.0μM) for only 1 h at 6 dpf swam faster with increasing PFOS concentration. Larvae exposed to 16.0 μM PFOS for 24 h periods from 1 to 121 hpf showed the highest incidence of malformations in the 97-121 hpf window. Continuous exposure to PFOS from 1 to 121 hpf resulted in a steady accumulation with no evidence of elimination. Our results further the understanding of the health risks of PFOS to aquatic organisms and identify additional research needed on PFOS toxicology.
doi:10.1016/j.aquatox.2010.02.003
PMCID: PMC4028132  PMID: 20171748
zebrafish embryo; PFOS; toxicity; behavior; window; uptake
14.  The synergistic effect of homocysteine and lipopolysaccharide on the differentiation and conversion of raw264.7 macrophages 
Background
Macrophages play pivotal roles in the progression of atherosclerosis (AS) and their heterogeneous differentiation patterns have been studied extensively. The classical subtype of activated macrophage, M1, promotes the progression of AS. Conversely, the alternative subtype of activated macrophage, M2, is regarded as a repressor of AS. Homocysteine (Hcy) may influence macrophage subtype polarization both in vivo and in vitro. Homocysteinemia (HHcy) is an independent risk factor in coronary heart disease and the effect of Hcy on macrophage differentiation has not been studied until now.
Methods
Different concentrations of Hcy in combination with a fixed concentration of lipopolysaccharide (LPS, 200 ng/mL) were used to treat RAW264.7 macrophages. Real-time PCR was used to detect and quantify RNA transcripts indicative of M1 and M2 differentiation. The efficacy and specificity for each chemical stimulant in inducing macrophage differentiation were also investigated. The M2 macrophages (anti-inflammatory subtype) induced using classical methods (IL-4, 10 ng/mL) were also treated with different concentrations of Hcy complemented with LPS. The synergistic effect of Hcy and LPS in the converting the M2 subtype to M1 was also studied.
Results
Macrophages can be induced to differentiate towards M1 by a combination of Hcy with LPS, with the strongest effect observed at an Hcy concentration of 50 μmol/L. After inducing macrophages to the M2 subtype using IL-4, treatment with both Hcy and LPS could elicit conversion from the M2 to M1 subtype.
Conclusion
Combined treatment with Hcy and LPS can induce the polarization of cultured RAW264.7 macrophages into the pro-inflammatory subtype, as well as promote subtype conversion from anti-inflammatory to pro-inflammatory.
doi:10.1186/1476-9255-11-13
PMCID: PMC4030071  PMID: 24855453
Homocysteine; Lipopolysaccharide; Macrophages; M1/M2 subtype; Polarization; Subtype conversion
15.  Biology of Ageing and Role of Dietary Antioxidants 
BioMed Research International  2014;2014:831841.
Interest in relationship between diet and ageing is growing. Research has shown that dietary calorie restriction and some antioxidants extend lifespan in various ageing models. On the one hand, oxygen is essential to aerobic organisms because it is a final electron acceptor in mitochondria. On the other hand, oxygen is harmful because it can continuously generate reactive oxygen species (ROS), which are believed to be the factors causing ageing of an organism. To remove these ROS in cells, aerobic organisms possess an antioxidant defense system which consists of a series of enzymes, namely, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). In addition, dietary antioxidants including ascorbic acid, vitamin A, vitamin C, α-tocopherol, and plant flavonoids are also able to scavenge ROS in cells and therefore theoretically can extend the lifespan of organisms. In this connection, various antioxidants including tea catechins, theaflavins, apple polyphenols, black rice anthocyanins, and blueberry polyphenols have been shown to be capable of extending the lifespan of fruit flies. The purpose of this review is to brief the literature on modern biological theories of ageing and role of dietary antioxidants in ageing as well as underlying mechanisms by which antioxidants can prolong the lifespan with focus on fruit flies as an model.
doi:10.1155/2014/831841
PMCID: PMC3996317  PMID: 24804252
16.  Accurate and Economical Detection of ALK Positive Lung Adenocarcinoma with Semiquantitative Immunohistochemical Screening 
PLoS ONE  2014;9(3):e92828.
Right detection of anaplastic lymphoma kinase (ALK) gene rearrangement is pivotal to selection of patients with lung adenocarcinoma for ALK-targeted therapy. We explored the potential of combination of immunohistochemistry (IHC) screening and fluorescence in situ hybridization (FISH) as an affordable practice. We analyzed 410 unselected lung adenocarcinomas by ALK IHC (D5F3 clone) and FISH. Some equivocal cases were further analyzed by RT-PCR. The EGFR mutation was detected by pyrosequencing assay. In total 368 cases which got all IHC, FISH, EGFR mutation results were eligible for analysis. Cases were evaluated as IHC score 3+ (n = 26), score 2+ (n = 9), score 1+ (n = 51), and score 0 (n = 282), respectively. 23 of 26 IHC 3+ and 5 of 9 IHC 2+ cases were FISH positive, whereas 3 of 26 IHC 3+, 4 of 9 IHC 2+ and all 333 IHC 1+/0 cases were FISH negative. If considering FISH as the standard, the sensitivity and specificity of ALK IHC 3+/2+ as ALK positive were 100% and 97.9%, respectively. Three IHC 3+ cases reported as FISH “negative” were actually ALK positive confirmed by ALK RT-PCR or re-detected. Based on the final classify, ALK IHC 3+/2+ was 100% sensitive and 98.8% specific. However, FISH was 90.3% sensitive and 100% specific. IHC 2+ was regarded as equivocal and need to be confirmed by FISH or RT-PCR. In the 368 cases, 8.4% cases had ALK positive, 52.2% cases had EGFR mutation, and only one case had a coexisting. Manually semiquantitative ALK IHC (primary antibody D5F3 coupled with secondary DAKO Envision system) used as the initial screening combined with auxiliary FISH confirmation is a reliable, economical approach to identify ALK positive lung adenocarcinoma. The IHC can find some ALK positive cases which would be missed by FISH only.
doi:10.1371/journal.pone.0092828
PMCID: PMC3965450  PMID: 24667320
17.  A Rim-Enhanced Mass with Central Cystic Changes on MR Imaging: How to Distinguish Breast Cancer from Inflammatory Breast Diseases? 
PLoS ONE  2014;9(3):e90355.
Objective
To evaluate the capacity of magnetic resonance imaging (MRI) to distinguish breast cancer from inflammatory breast diseases manifesting as a rim-enhanced mass with central cystic changes.
Materials and Methods
Forty cases of breast cancer and 52 of inflammatory breast diseases showing a rim-enhanced mass with central cystic changes were retrospectively reviewed. All cases underwent dynamic contrast-enhanced MRI and 31 of them underwent diffusion-weighted imaging (DWI). Morphological features, dynamic parameters and apparent diffusion coefficient (ADC) values were comparatively analyzed using univariate analysis and binary logistic regression analysis.
Results
Breast cancer had a significantly thicker wall than the inflammatory breast diseases (P<0.001) while internal enhancing septa were more common in inflammatory breast diseases (P = 0.003). On DWI, 86.7% of breast cancers demonstrate a peripheral hyperintensity whereas 93.8% of inflammatory breast diseases had a central hyperintensity (P<0.001). Compared to the inflammatory breast diseases, breast cancers had a lower ADC value for the wall (1.09×10−3 mm2/s vs 1.42×10−3 mm2/s, P<0.001) and a higher ADC value for the central part (1.94×10−3 mm2/s vs 1.05×10−3 mm2/s, P<0.001).
Conclusions
Both breast cancer and inflammatory breast diseases could present as a rim-enhanced mass with central cystic changes on MRI. Integrated analysis of the MR findings can allow for an accurate differential diagnosis.
doi:10.1371/journal.pone.0090355
PMCID: PMC3943946  PMID: 24598845
18.  Evaluating the Potential Bioactivity of a Novel Compound ER1626 
PLoS ONE  2014;9(1):e86509.
Background
ER1626, a novel compound, is a derivate of indeno-isoquinoline ketone. This study was designed to evaluate the biological activity and potential anti-tumor mechanism of ER1626.
Method
MTT assay, scratch assay and flow cytometry were used to determine cell proliferation, cell migration and cell cycle distribution as well as cell apoptosis on human breast cancer MCF-7 cells and endometrial cancer Ishikawa cells. We also explored the antiangiogenic effect of ER1626 on HUVEC cells and chicken embryos. The expression of estrogen receptor protein was investigated with western-blot analysis.
Results
ER1626 down-regulated the expression of estrogen receptor α protein and up-regulated β protein in MCF-7 and Ishikawa cells. The value of IC50 of ER1626 on MCF-7 and Ishikawa cells were respectively 8.52 and 3.08 µmol/L. Meanwhile, ER1626 decreased VEGF secretion of MCF-7 and Ishikawa cells, disturbed the formation of VEGF-stimulated tubular structure in HUVEC cells, and inhibited the angiogenesis on the chicken chorioallantoic membrane. Scratch assay revealed that ER1626 suppressed the migration of MCF-7, Ishikawa and HUVEC cells. In addition to induction tumor cell apoptosis, ER1626 arrested cell cycle in G1/G0 phase in MCF-7 cells and G2/M phase in Ishikawa cells.
Conclusion
In conclusion, our results demonstrated that ER1626 has favorable bioactivities to be a potential candidate against breast cancer and angiogenesis.
doi:10.1371/journal.pone.0086509
PMCID: PMC3903524  PMID: 24475135
19.  The temporal dynamics of visual working memory guidance of selective attention 
The biased competition model proposes that there is top-down directing of attention to a stimulus matching the contents of working memory (WM), even when the maintenance of a WM representation is detrimental to target relevant performance. Despite many studies elucidating that spatial WM guidance can be present early in the visual processing system, whether visual WM guidance also influences perceptual selection remains poorly understood. Here, we investigated the electrophysiological correlates of early guidance of attention by WM in humans. Participants were required to perform a visual search task while concurrently maintaining object representations in their visual WM. Behavioral results showed that response times (RTs) were longer when the distractor in the visual search task was held in WM. The earliest WM guidance effect was observed in the P1 component (90–130 ms), with match trials eliciting larger P1 amplitude than mismatch trials. A similar result was also found in the N1 component (160–200 ms). These P1 and N1 effects could not be attributed to bottom-up perceptual priming from the presentation of a memory cue, because there was no significant difference in early event-related potential (ERP) component when the cue was merely perceptually identified but not actively held in WM. Standardized Low Resolution Electrical Tomography Analysis (sLORETA) showed that the early WM guidance occurred in the occipital lobe and the N1-related activation occurred in the parietal gyrus. Time-frequency data suggested that alpha-band event-related spectral perturbation (ERSP) magnitudes increased under the match condition compared with the mismatch condition only when the cue was held in WM. In conclusion, the present study suggests that the reappearance of a stimulus held in WM enhanced activity in the occipital area. Subsequently, this initial capture of attention by WM could be inhibited by competing visual inputs through attention re-orientation, reflecting by the alpha-band rhythm.
doi:10.3389/fnbeh.2014.00345
PMCID: PMC4176477  PMID: 25309377
working memory; biased competition model; event-related potential (ERP); sLORETA; alpha-band rhythm
20.  Effects of Acupuncture on CCL2 and CXCL8 Expression and the Subset of uNK Cells in Rats with Embryo Implantation Failure 
The present study was designed to investigate the efficacy and mechanism of acupuncture treatment on embryo implantation failure in rats. The pregnant rats were randomized into normal group (N), implantation failure group (M), acupuncture treatment group (A), and progestin treatment group (W). The embryo implantation failure model was established by mifepristone. Efficacy of acupuncture treatment was evaluated by the number of implanted embryos. The expression of CCL2 and CXCL8 and the subset of uterine natural killer cells in the endometrium were detected. We demonstrated that the number of implanted embryos was dramatically reduced after mifepristone (M group) treatment, while the acupuncture (A group) and progestin (W group) treatments significantly rescued impaired embryo implantation. The protein and mRNA expressions of CCL2 and CXCL8 were significantly reduced by mifepristone treatment, but the attenuated expression of CCL2 and CXCL8 was markedly reversed by acupuncture or progestin treatment. More importantly, acupuncture and progestin could markedly increase the subset of uNK cells in rats with embryo implantation failure. These evidences suggest that acupuncture is able to modulate the endometrial immune microenvironment and thus improve embryo implantation in pregnant rats, which provides solid experimental evidence for the curative effect of acupuncture treatment on infertility.
doi:10.1155/2013/678390
PMCID: PMC3874941  PMID: 24396391
21.  TLQP-21 Protects Human Umbilical Vein Endothelial Cells against High-Glucose-Induced Apoptosis by Increasing G6PD Expression 
PLoS ONE  2013;8(11):e79760.
Hyperglycemia causes oxidative stress that could damage vascular endothelial cells, leading to cardiovascular complications. The Vgf gene was identified as a nerve growth factor-responsive gene, and its protein product, VGF, is characterized by the presence of partially cleaved products. One of the VGF-derived peptides is TLQP-21, which is composed of 21 amino acids (residues 556–576). Past studies have reported that TLQP-21 could stimulate insulin secretion in pancreatic cells and protect these cells from apoptosis, which suggests that TLQP-21 has a potential function in diabetes therapy. Here, we explore the protective role of TLQP-21 against the high glucose-mediated injury of vascular endothelial cells. Using human umbilical vascular endothelial cells (HUVECs), we demonstrated that TLQP-21 (10 or 50 nM) dose-dependently prevented apoptosis under high-glucose (30 mmol/L) conditions (the normal glucose concentration is 5.6 mmol/L). TLQP-21 enhanced the expression of NAPDH, resulting in upregulation of glutathione (GSH) and a reduction in the levels of reactive oxygen species (ROS). TLQP-21 also upregulated the expression of glucose-6-phosphate dehydrogenase (G6PD), which is known as the main source of NADPH. Knockdown of G6PD almost completely blocked the increase of NADPH induced by TLQP-21, indicating that TLQP-21 functions mainly through G6PD to promote NADPH generation. In conclusion, TLQP-21 could increase G6PD expression, which in turn may increase the synthesis of NADPH and GSH, thereby partially restoring the redox status of vascular endothelial cells under high glucose injury. We propose that TLQP-21 is a promising drug for diabetes therapy.
doi:10.1371/journal.pone.0079760
PMCID: PMC3836798  PMID: 24278172
22.  Concurrent primary carcinoid tumor arising within mature teratoma and clear cell renal cell carcinoma in the horseshoe kidney: report of a rare case and review of the literature 
Primary carcinoid tumor arising in a mature teratoma of the horseshoe kidney is exceptionally rare and only 4 such cases have been reported in the world literature to date. The simultaneous occurrence of different subtypes of renal cell carcinoma (RCC) or RCC coexistence with non-RCC neoplasms from the same kidney is unusual and infrequently reported. Herein we report a case of primary carcinoid tumor arising within mature teratoma, concurrent with a clear cell RCC in the horseshoe kidney of a 37-year-old man. Histologically, both the carcinoid tumor and clear cell RCC demonstrated the characteristic morphology in their classic forms. In addition to the carcinoid tumor, the mature teratoma consisted of variably sized, large cystic spaces lined by cytologically bland mucinous columnar epithelium, pseudostratified columnar epithelium, ciliated epithelium and mature smooth muscle fibers were also identified within the cystic wall. Furthermore, foci of round, small nodules composed of mature prostatic acinus were noted in the teratoma which was confirmed by exhibiting strong immunoreactivity for prostate specific antigen. The present case serves to expand the histologic component that may be encountered in the mature terotoma of the kidney and further broadens the spectrum of primary tumors occurring in the horseshoe kidney.
PMCID: PMC3816830  PMID: 24228123
Kidney; carcinoid tumor; mature teratoma; horseshoe kidney; prostate tissue
23.  An adult case of systemic Epstein-Barr virus-positive T/natural killer-cell lymphoproliferative disorder with good outcome 
Epstein-Barr virus-positive T/natural killer (NK)-cell lymphoproliferative disorder (EBV+T/NK LPD) encompasses a heterogeneous group of disorders that have a common feature with excessive lymphoid proliferation of mainly T cells and/or NK cells. This disease is rare, predominantly affects children and young adults, and associated with high mortality. Herein, we report a case of EBV+T/NK LPD that occurred in an old woman with good outcome. The patient presented with fever, splenomegaly, and pancytopenia. Computed tomography (CT) scan of the abdomen showed splenomegaly. The clinical impression was a malignant tumor of spleen, so splenectomy was performed. Microscopically, the architecture of the spleen was preserved. The white pulp Malpighian corpuscles were atrophied. The red pulp showed intact sinusoids and pulp cords with increased cellular infiltrate. The proliferating lymphoid cells were mostly small lymphoid cells with minimal or no nuclear atypia, mixed with rare medium-sized or large cells. Immunohistochemical study and in-situ hybridization showed that the EBER-positive lymphoid cells were positive for CD3 and CD56. They were also positive for cytotoxic molecules, such as T-cell restricted intracellular antigen (TIA1), granzyme B. The case exhibited polyclonal rearrangement of T-cell receptor gene (TCR) by polymerase chain reaction (PCR) studies. Without radiotherapy and chemotherapy, the patient is alive and well with no evidence of disease 25 months after surgery.
PMCID: PMC3816837  PMID: 24228130
Epstein-Barr virus; T/natural killer-cell; lymphoproliferative disorder
24.  Related Biological Research in the Interface between Bone Cement and Bone after Percutaneous Vertebroplasty 
Percutaneous vertebroplasty (PVP) is widely used in the treatment of painful osteoporotic vertebral compression fractures with the injection of PMMA cement, and the controversy for PMMA damage to the osteoporotic bone tissue and to affect the fractures repairing never stops. 72 old female rabbits, each age 3.0~3.5 y, rabbits were assigned randomly to two groups of thirty-six each; PMMA cement were injected into vertebral body in rabbits via mimic PVP, sacrificed at 1 h, 24 h, 3 d, 7 d, 4 w, and 12 w. The expression VEGF and collagen type I, the tissue response, and repair reaction in the interface between PMMA and bone tissue were observed dynamically with RT-PCR and western blot technique; the osteocalcin expression were studied by immunohistochemistry. Compared with the control group, the expression of collagen I increased at 1 hour and was higher from 24 h to 3 d. From 4 weeks to 12 weeks after injection of PMMA. The expression of VEGF decreased at 1 hour and 24 hours, significantly increased at 3 days, decreased once again at 7 days, then increased significantly at 4–12 weeks. The osteocalcin expression continued to increase during 4 to 12 week. PMMA would not cause local bone permanent necrosis, and interface injury repairing cycle could be prolonged in a vertebroplasty.
doi:10.1155/2013/109784
PMCID: PMC3814054  PMID: 24222763
25.  Principal Feature Analysis: A Multivariate Feature Selection Method for fMRI Data 
Brain decoding with functional magnetic resonance imaging (fMRI) requires analysis of complex, multivariate data. Multivoxel pattern analysis (MVPA) has been widely used in recent years. MVPA treats the activation of multiple voxels from fMRI data as a pattern and decodes brain states using pattern classification methods. Feature selection is a critical procedure of MVPA because it decides which features will be included in the classification analysis of fMRI data, thereby improving the performance of the classifier. Features can be selected by limiting the analysis to specific anatomical regions or by computing univariate (voxel-wise) or multivariate statistics. However, these methods either discard some informative features or select features with redundant information. This paper introduces the principal feature analysis as a novel multivariate feature selection method for fMRI data processing. This multivariate approach aims to remove features with redundant information, thereby selecting fewer features, while retaining the most information.
doi:10.1155/2013/645921
PMCID: PMC3793313  PMID: 24171045

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