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1.  Gene–environment interaction between adiponectin gene polymorphisms and environmental factors on the risk of diabetic retinopathy 
Aims/Introduction
To evaluate whether the adiponectin gene is associated with diabetic retinopathy (DR) risk and interaction with environmental factors modifies the DR risk, and to investigate the relationship between serum adiponectin levels and DR.
Materials and Methods
Four adiponectin polymorphisms were evaluated in 372 DR cases and 145 controls. Differences in environmental factors between cases and controls were evaluated by unconditional logistic regression analysis. The model-free multifactor dimensionality reduction method and traditional multiple regression models were applied to explore interactions between the polymorphisms and environmental factors.
Results
Using the Bonferroni method, we found no significant associations between four adiponectin polymorphisms and DR susceptibility. Multivariate logistic regression found that physical activity played a protective role in the progress of DR, whereas family history of diabetes (odds ratio 1.75) and insulin therapy (odds ratio 1.78) were associated with an increased risk for DR. The interaction between the C-11377 G (rs266729) polymorphism and insulin therapy might be associated with DR risk. Family history of diabetes combined with insulin therapy also increased the risk of DR. No adiponectin gene polymorphisms influenced the serum adiponectin levels. Serum adiponectin levels did not differ between the DR group and non-DR group.
Conclusions
No significant association was identified between four adiponectin polymorphisms and DR susceptibility after stringent Bonferroni correction. The interaction between C-11377G (rs266729) polymorphism and insulin therapy, as well as the interaction between family history of diabetes and insulin therapy, might be associated with DR susceptibility.
doi:10.1111/jdi.12249
PMCID: PMC4296704  PMID: 25621134
Adiponectin; Diabetic retinopathy; Gene–environment interaction
2.  Vimentin-Mediated Steroidogenesis Induced by Phthalate Esters: Involvement of DNA Demethylation and Nuclear Factor κB 
PLoS ONE  2016;11(1):e0146138.
Di-n-butyl phthalate (DBP) and its active metabolite, monobutyl phthalate (MBP) are the most common endocrine disrupting chemicals. Many studies indicate that high-doses of DBP and/or MBP exhibit toxicity on testicular function, however, little attention have been paid to the effects of low levels of DBP/MBP on steroidogenesis. As we all know, the steroidogenic acute regulatory protein (StAR) is a key regulator involved in the steroidogenesis. Here we found that, in addition to StAR, MBP/DBP increased the steroidogenesis by a cytoskeletal protein, vimentin. Briefly, in murine adrenocortical tumor (Y1) and the mouse Leydig tumor (MLTC-1) cells, vimentin regulated the secretion of progesterone. When these two cells were exposure to MBP, the DNA demethylation in the vimentin promoter was observed. In addition, MBP also induced the activation of nuclear factor kappa B (NF-κB, a transcriptional regulator of vimentin). These two processes improved the transcriptional elevation of vimentin. Knockdown of NF-κB/vimentin signaling blocked the DBP/MBP-induced steroidogenesis. These in vitro results were also confirmed via an in vivo model. By identifying a mechanism whereby DBP/MBP regulates vimentin, our results expand the understanding of the endocrine disrupting potential of phthalate esters.
doi:10.1371/journal.pone.0146138
PMCID: PMC4706347  PMID: 26745512
3.  Spin transport in undoped InGaAs/AlGaAs multiple quantum well studied via spin photocurrent excited by circularly polarized light 
The spin diffusion and drift at different excitation wavelengths and different temperatures have been studied in undoped InGaAs/AlGaAs multiple quantum well (MQW). The spin polarization was created by optical spin orientation using circularly polarized light, and the reciprocal spin Hall effect was employed to measure the spin polarization current. We measured the ratio of the spin diffusion coefficient to the mobility of spin-polarized carriers. From the wavelength dependence of the ratio, we found that the spin diffusion and drift of holes became as important as electrons in this undoped MQW, and the ratio for light holes was much smaller than that for heavy holes at room temperature. From the temperature dependence of the ratio, the correction factors for the common Einstein relationship for spin-polarized electrons and heavy holes were firstly obtained to be 93 and 286, respectively.
doi:10.1186/s11671-015-1218-3
PMCID: PMC4705080  PMID: 26744148
Spin diffusion; Spin drift; The circularly polarized light; The reciprocal spin Hall effect
4.  Efficient Genome Editing in Clostridium cellulolyticum via CRISPR-Cas9 Nickase 
Applied and Environmental Microbiology  2015;81(13):4423-4431.
The CRISPR-Cas9 system is a powerful and revolutionary genome-editing tool for eukaryotic genomes, but its use in bacterial genomes is very limited. Here, we investigated the use of the Streptococcus pyogenes CRISPR-Cas9 system in editing the genome of Clostridium cellulolyticum, a model microorganism for bioenergy research. Wild-type Cas9-induced double-strand breaks were lethal to C. cellulolyticum due to the minimal expression of nonhomologous end joining (NHEJ) components in this strain. To circumvent this lethality, Cas9 nickase was applied to develop a single-nick-triggered homologous recombination strategy, which allows precise one-step editing at intended genomic loci by transforming a single vector. This strategy has a high editing efficiency (>95%) even using short homologous arms (0.2 kb), is able to deliver foreign genes into the genome in a single step without a marker, enables precise editing even at two very similar target sites differing by two bases preceding the seed region, and has a very high target site density (median interval distance of 9 bp and 95.7% gene coverage in C. cellulolyticum). Together, these results establish a simple and robust methodology for genome editing in NHEJ-ineffective prokaryotes.
doi:10.1128/AEM.00873-15
PMCID: PMC4475897  PMID: 25911483
5.  Reprogramming somatic cells to cells with neuronal characteristics by defined medium both in vitro and in vivo 
Cell Regeneration  2015;4:12.
Background
Currently, direct conversion from somatic cells to neurons requires virus-mediated delivery of at least one transcriptional factor or a combination of several small-molecule compounds. Delivery of transcriptional factors may affect genome stability, while small-molecule compounds may require more evaluations when applied in vivo. Thus, a defined medium with only conventional growth factors or additives for cell culture is desirable for inducing neuronal trans-differentiation.
Results
Here, we report that a defined medium (5C) consisting of basic fibroblast growth factor (bFGF), N2 supplement, leukemia inhibitory factor, vitamin C (Vc), and β-mercaptoethanol (βMe) induces the direct conversion of somatic cells to cells with neuronal characteristics. Application of 5C medium converted mouse embryonic fibroblasts (MEFs) into TuJ+ neuronal-like cells, which were capable of survival after being transplanted into the mouse brain. The same 5C medium could convert primary rat astrocytes into neuronal-like cells with mature electrophysiology characteristics in vitro and facilitated the recovery of brain injury, possibly by inducing similar conversions, when infused into the mouse brain in vivo. Crucially, 5C medium could also induce neuronal characteristics in several human cell types.
Conclusions
In summary, this 5C medium not only provides a means to derive cells with neuronal characteristics without viral transfection in vitro but might also be useful to produce neurons in vivo for neurodegenerative disease treatment.
Electronic supplementary material
The online version of this article (doi:10.1186/s13619-015-0027-6) contains supplementary material, which is available to authorized users.
doi:10.1186/s13619-015-0027-6
PMCID: PMC4696146  PMID: 26719791
Neurons; Somatic cells; Astrocytes; Trans-differentiation; Defined medium
6.  Prognostic Significance and Molecular Features of Colorectal Mucinous Adenocarcinomas 
Medicine  2015;94(51):e2350.
Supplemental Digital Content is available in the text
Abstract
Mucinous adenocarcinoma (MC) is a special histology subtype of colorectal adenocarcinoma. The survival of MC is controversial and the prognostic biomarkers of MC remain unclear. To analyze prognostic significance and molecular features of colorectal MC. This study included 755,682 and 1001 colorectal cancer (CRC) patients from Surveillance, Epidemiology, and End Results program (SEER, 1973–2011), and Linköping Cancer (LC, 1972–2009) databases. We investigated independently the clinicopathological characteristics, survival, and variety of molecular features from these 2 databases. MC was found in 9.3% and 9.8% patients in SEER and LC, respectively. MC was more frequently localized in the right colon compared with nonmucinous adenocarcinoma (NMC) in both SEER (57.7% vs 37.2%, P < 0.001) and LC (46.9% vs 27.7%, P < 0.001). Colorectal MC patients had significantly worse cancer-specific survival (CSS) than NMC patients (SEER, P < 0.001; LC, P = 0.026), prominently in stage III (SEER, P < 0.001; LC, P = 0.023). The multivariate survival analysis showed that MC was independently related to poor prognosis in rectal cancer patients (SEER, hazard ratios [HR], 1.076; 95% confidence intervals [CI], 1.057–1.096; P < 0.001). In LC, the integrated analysis of genetic and epigenetic features showed that that strong expression of PINCH (HR, 3.954; 95% CI, 1.493–10.47; P = 0.013) and weak expression of RAD50 (HR 0.348, 95% CI, 0.106–1.192; P = 0.026) were significantly associated with poor CSS of colorectal MC patients. In conclusion, the colorectal MC patients had significantly worse CSS than NMC patients, prominently in stage III. MC was an independent prognostic factor associated with worse survival in rectal cancer patients. The PINCH and RAD50 were prognostic biomarkers for colorectal MC patients.
doi:10.1097/MD.0000000000002350
PMCID: PMC4697997  PMID: 26705231
7.  Seven-day triple therapy is a better choice for Helicobacter pylori eradication in regions with low antibiotic resistance 
World Journal of Gastroenterology  2015;21(46):13073-13079.
AIM: To investigate whether 7-d triple therapies are still valid in populations with low levels of resistance.
METHODS: A total of 1106 Helicobacter pylori (H. pylori)-positive patients were divided into three groups, each of which received one type of 7-d triple therapy. Therapeutic outcomes of the patients were assessed by the 13C-urea breath test at 8 wk after treatment. The susceptibility of H. pylori to antibiotics was determined by an agar-dilution method. Data analysis was performed by χ2 tests.
RESULTS: The eradication rates in groups A, B and C were 90.71% (332/366), 90.46% (313/346) and 90.87% (189/208), respectively (P = 0.986). The resistance rates were 8.91% for clarithromycin, 14.78% for levofloxacin and 0% for amoxicillin. The eradication rate was significantly different between clarithromycin- and levofloxacin-resistant patients (P < 0.05) in group A. Patients whose treatment failed in group A also had a higher clarithromycin resistance rate than did successive patients (P = 0.034). However, levofloxacin resistance had no obvious influence on the eradication rate. Furthermore, three main antibiotics (clarithromycin, levofloxacin and amoxicillin) had lower DID (defined daily dose per 1000 inhabitants per day) in this city.
CONCLUSION: Clarithromycin resistance is the main reason for the failure of 7-d triple therapy. In populations with low levels of resistance, a 7-d triple therapy is a viable choice. The choice of therapy should not be influenced by conditions in high antibiotic resistance regions.
doi:10.3748/wjg.v21.i46.13073
PMCID: PMC4674725  PMID: 26672777
Helicobacter pylori; Seven-day triple therapy; Eradication rate; Clarithromycin resistance; Levofloxacin resistance
8.  Effect of Post-Infiltration Soil Aeration at Different Growth Stages on Growth and Fruit Quality of Drip-Irrigated Potted Tomato Plants (Solanum lycopersicum) 
PLoS ONE  2015;10(12):e0143322.
Soil hydraulic principles suggest that post-infiltration hypoxic conditions would be induced in the plant root-zone for drip-irrigated tomato production in small pots filled with natural soil. No previous study specifically examined the response of tomato plants (Solanum lycopersicum) at different growth stages to low soil aeration under these conditions. A 2 × 6 factorial experiment was conducted to quantify effects of no post-infiltration soil aeration versus aeration during 5 different periods (namely 27–33, 34–57, 58–85, 86–99, and 27–99 days after sowing), on growth and fruit quality of potted single tomato plants that were sub-surface trickle-irrigated every 2 days at 2 levels. Soil was aerated by injecting 2.5 liters of air into each pot through the drip tubing immediately after irrigation. Results showed that post-infiltration aeration, especially during the fruit setting (34–57 DAS) and enlargement (58–85 DAS) growth stages, can positively influence the yield, root dry weight and activity, and the nutritional (soluble solids and vitamin C content), taste (titratable acidity), and market quality (shape and firmness) of the tomato fruits. Interactions between irrigation level and post-infiltration aeration on some of these fruit quality parameters indicated a need for further study on the dynamic interplay of air and water in the root zone of the plants under the conditions of this experiment.
doi:10.1371/journal.pone.0143322
PMCID: PMC4668012  PMID: 26630675
9.  Clinical phenotype and allergen sensitization in the first 2 years as predictors of atopic disorders at age 5 years 
Introduction
From a birth cohort of at-risk Asian infants, we prospectively investigated the role of early onset allergen sensitization and clinical phenotypes as risk factors for atopic disorders at the age of 5 years.
Methods and materials
The study recruited 253 families with a history of allergic disease in a first degree relative from an antenatal clinic in Singapore. The children were followed prospectively to assess clinical outcomes and skin prick test was performed at 2 and 5 years of age.
Results
Allergen sensitization (food and/or house dust mites) alone at 2 years of age was not associated with increased risk of wheeze and eczema at 5 years. However, the clinical phenotype (eczema and wheeze) with or without the presence of concomitant allergen sensitization at 2 years increased this risk. For eczema, eczema alone at year 2 increased the risk of eczema at year 5 (adjOR = 7.1; 95 % CI: 1.8–27.8) and this was further increased by the presence of allergen sensitization (adjOR = 25.4; 95 % CI: 4.7–138.5) and the concomitant presence of both wheeze and allergen sensitization (adjOR = 64.9; 95 % CI: 4.7–900.0). For wheeze, wheeze alone at 2 years (adjOR = 4.5; 95 % CI: 1.4 -14.8), and wheeze with concomitant allergen sensitization and eczema (adjOR = 13.9; 95 % CI: 1.2–168.5) increased the risk of wheeze at 5 years. The exception was rhinitis, where allergen sensitization alone at 2 years (adjOR = 5.6; 95 % CI: 1.1–29.2) increased the risk of rhinitis at 5 years. Early onset of eczema at 2 years also increased the risk of rhinitis (adjOR = 6.8; 95 % CI: 2.0–23.1).
Conclusion
In this Asian birth cohort, the clinical phenotype (eczema and wheeze) with or without concomitant allergen sensitization in the first 2 years of life were strong predictors of atopic disorders at 5 years.
doi:10.1186/s40413-015-0082-z
PMCID: PMC4667513  PMID: 26664574
Eczema; Wheeze; Rhinitis; Allergen sensitization
10.  An Aggregation-Induced-Emission Platform for Direct Visualization of Interfacial Dynamic Self-Assembly** 
An in-depth understanding of dynamic interfacial self-assembly processes is essential for a wide range of topics in theoretical physics, materials design, and biomedical research. However, direct monitoring of such processes is hampered by the poor imaging contrast of a thin interfacial layer. We report in situ imaging technology capable of selectively highlighting self-assembly at the phase boundary in real time by employing the unique photophysical properties of aggregation-induced emission. Its application to the study of breath-figure formation, an immensely useful yet poorly understood phenomenon, provided a mechanistic model supported by direct visualization of all main steps and fully corroborated by simulation and theoretical analysis. This platform is expected to advance the understanding of the dynamic phase-transition phenomena, offer insights into interfacial biological processes, and guide development of novel self-assembly technologies.
doi:10.1002/anie.201408757
PMCID: PMC4370284  PMID: 25363745
11.  IsoDOT Detects Differential RNA-isoform Expression/Usage with respect to a Categorical or Continuous Covariate with High Sensitivity and Specificity 
We have developed a statistical method named IsoDOT to assess differential isoform expression (DIE) and differential isoform usage (DIU) using RNA-seq data. Here isoform usage refers to relative isoform expression given the total expression of the corresponding gene. IsoDOT performs two tasks that cannot be accomplished by existing methods: to test DIE/DIU with respect to a continuous covariate, and to test DIE/DIU for one case versus one control. The latter task is not an uncommon situation in practice, e.g., comparing the paternal and maternal alleles of one individual or comparing tumor and normal samples of one cancer patient. Simulation studies demonstrate the high sensitivity and specificity of IsoDOT. We apply IsoDOT to study the effects of haloperidol treatment on the mouse transcriptome and identify a group of genes whose isoform usages respond to haloperidol treatment.
doi:10.1080/01621459.2015.1040880
PMCID: PMC4662594  PMID: 26617424
RNA-seq; isoform; penalized regression; differential isoform expression; differential isoform usage
12.  The oncogenic STP axis promotes triple-negative breast cancer via degradation of the REST tumor suppressor 
Cell reports  2014;9(4):1318-1332.
SUMMARY
Defining the molecular networks that drive breast cancer has led to therapeutic interventions and improved patient survival. However, the aggressive triple-negative breast cancer subtype (TNBC) remains recalcitrant to targeted therapies because its molecular etiology is poorly defined. In this study, we used a forward genetic screen to discover an oncogenic network driving human TNBC. SCYL1, TEX14, and PLK1 (“STP axis”) cooperatively trigger degradation of the REST tumor suppressor protein, a frequent event in human TNBC. The STP axis induces REST degradation by phosphorylating a conserved REST phospho-degron and bridging REST interaction with the ubiquitin-ligase βTRCP. Inhibition of the STP axis leads to increased REST protein levels and impairs TNBC transformation, tumor progression, and metastasis. Expression of the STP axis correlates with low REST protein levels in human TNBCs and poor clinical outcome for TNBC patients. Our findings demonstrate that the STP-REST axis is a new molecular driver of human TNBC.
Graphical Abstract
doi:10.1016/j.celrep.2014.10.011
PMCID: PMC4427000  PMID: 25453754
13.  Influence of Acarbose on Plasma Glucose Fluctuations in Insulin-Treated Patients with Type 2 Diabetes: A Pilot Study 
Background and Aims. To evaluate the effect of adding acarbose on glycemic excursions measured by continuous glucose monitoring system (CGMS) in patients with type 2 diabetes mellitus (T2DM) already on insulin therapy. Materials and Methods. This was an opened and unblended study. 134 patients with T2DM were recruited. After initial rapidly corrected hyperglycaemia by continuous subcutaneous insulin infusion (CSII) for 7 d, a 4–6-day premixed insulin titration period subsequently followed. Patients were then randomized 1 : 1 to acarbose plus insulin group or insulin therapy group for 2 weeks. CGMS was used to measure glucose fluctuations for at least 3 days after therapy cessation. Results. Patients in acarbose plus insulin group achieved a significant improvement of MAGE compared to that of insulin therapy only group (5.56 ± 2.16 versus 7.50 ± 3.28 mmol/L, P = 0.044), accompanied by a significant decrease in the incremental AUC of plasma glucose concentration above 10.0 mmol/L (0.5 [0.03, 0.9] versus 0.85 [0.23,1.4]  mmol/L per day, P = 0.037). Conclusions. Add-on acarbose to insulin therapy further improves glucose fluctuation in patients with T2DM. This study was registered with ClinicalTrials.gov registration number ChiCTR-TRC-11001218.
doi:10.1155/2015/903524
PMCID: PMC4658413  PMID: 26640487
14.  The association between XRCC1 Arg399Gln polymorphism and risk of leukemia in different populations: a meta-analysis of case-control studies 
OncoTargets and therapy  2015;8:3277-3287.
Background
Associations between Arg399Gln single-nucleotide polymorphism (SNP) in the XRCC1 gene and leukemia susceptibility have been studied extensively, however, the results are inconsistent. The aim of this study was to determine these associations using meta-analytical methods.
Methods
A meta-analysis was performed to examine the associations between XRCC1 Arg399-Gln SNP and leukemia risk. A literature search of PubMed and Web of Science databases was conducted to identify relevant studies published up to March 10, 2015. The references of the retrieved articles were also screened. All the statistical analyses were conducted using Review Manager software.
Results
The XRCC1 Arg399Gln SNP was found to be associated with increased childhood risk of acute lymphoblastic leukemia among Asians under the dominant (odds ratio [OR] 2.11, 95% confidence interval [CI] 1.50–2.97, P<0.0001), allele contrast (OR 1.72, 95% CI 1.33–2.23, P<0.0001), and homozygote contrast (OR 2.34, 95% CI 1.25–4.36, P=0.008) models. However, no association was found in Caucasians between the SNP and risk of either chronic myeloid leukemia or chronic lymphocytic leukemia under any contrast model.
Conclusion
The findings of the current meta-analysis indicate that the XRCC1 Arg399Gln SNP is a risk factor for childhood lymphoblastic leukemia in Asians.
doi:10.2147/OTT.S92752
PMCID: PMC4644162  PMID: 26609240
Arg399Gln; AML; ALL; CML; CLL; susceptibility
15.  Estimating PM2.5 Concentrations in Xi'an City Using a Generalized Additive Model with Multi-Source Monitoring Data 
PLoS ONE  2015;10(11):e0142149.
Particulate matter with an aerodynamic diameter <2.5 μm (PM2.5) represents a severe environmental problem and is of negative impact on human health. Xi'an City, with a population of 6.5 million, is among the highest concentrations of PM2.5 in China. In 2013, in total, there were 191 days in Xi’an City on which PM2.5 concentrations were greater than 100 μg/m3. Recently, a few studies have explored the potential causes of high PM2.5 concentration using remote sensing data such as the MODIS aerosol optical thickness (AOT) product. Linear regression is a commonly used method to find statistical relationships among PM2.5 concentrations and other pollutants, including CO, NO2, SO2, and O3, which can be indicative of emission sources. The relationships of these variables, however, are usually complicated and non-linear. Therefore, a generalized additive model (GAM) is used to estimate the statistical relationships between potential variables and PM2.5 concentrations. This model contains linear functions of SO2 and CO, univariate smoothing non-linear functions of NO2, O3, AOT and temperature, and bivariate smoothing non-linear functions of location and wind variables. The model can explain 69.50% of PM2.5 concentrations, with R2 = 0.691, which improves the result of a stepwise linear regression (R2 = 0.582) by 18.73%. The two most significant variables, CO concentration and AOT, represent 20.65% and 19.54% of the deviance, respectively, while the three other gas-phase concentrations, SO2, NO2, and O3 account for 10.88% of the total deviance. These results show that in Xi'an City, the traffic and other industrial emissions are the primary source of PM2.5. Temperature, location, and wind variables also non-linearly related with PM2.5.
doi:10.1371/journal.pone.0142149
PMCID: PMC4634950  PMID: 26540446
16.  What Are the Results Using the Modified Trapdoor Procedure to Treat Chondroblastoma of the Femoral Head? 
Background
Treatment of chondroblastoma in the femoral head is challenging owing to the particular location and its aggressive nature. There is little published information to guide the surgeon regarding the appropriate approach to treating a chondroblastoma in this location. We developed a modified trapdoor procedure to address this issue. The primary modification is that the window surface of the femoral head is covered by the ligamentum teres rather than cartilage as in the traditional procedure.
Questions/purposes
We assessed (1) the clinical presentation of chondroblastoma of the femoral head and treatment results with the modified trapdoor procedure in terms of (2) the frequency of local recurrence, (3) complications, and (4) functional outcomes using the Musculoskeletal Tumor Society (MSTS) score.
Methods
Between 1999 and 2010, we treated 14 patients for chondroblastoma of the femoral head. All patients received the modified trapdoor procedure. Of those, 13 were available for followup at a minimum of 36 months (mean, 66 months; range, 36–117 months) and one patient was lost to followup. There were nine males and four females, with a mean age of 18 years (range, 9–29 years). Clinical features were ascertained by chart and radiographic review, and recurrence, complications, and functional outcomes (MSTS score) were recorded from chart review. Patterns of bone destruction were evaluated using the Lodwick classification, which ranges from IA (geographic appearance with sclerotic rim) to III (permeative appearance).
Results
The symptoms at diagnosis were pain in nine patients and discomfort in four. The mean duration of symptom was 11 months (range, 1–36 months). The physis was open in two patients, closing in one, and closed in 10. The patterns of bone destruction were evaluated as Lodwick Class IA in six patients, Lodwick Class IB in five, and Lodwick Class IC in two. At latest followup, no local recurrence was observed. Two patients had postoperative complications. One had avascular necrosis of the femoral head and was treated with prosthesis replacement. The other had asymptomatic heterotopic ossification in the surgical field. The mean MSTS score was 29.6 (range, 28–30).
Conclusions
Based on this small series, we believe our modified trapdoor procedure is a safe, effective means of treating a chondroblastoma in the femoral head, but additional clinical evaluation with more patients is necessary to confirm our findings.
Level of Evidence
Level IV, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-014-3771-y
PMCID: PMC4182374  PMID: 25115583
17.  Severe Hypoglycemia Caused by Recurrent Sarcomatoid Carcinoma in the Pelvic Cavity 
Medicine  2015;94(42):e1577.
Abstract
Nonislet cell tumor hypoglycemia (NICTH) is a paraneoplastic syndrome characterized by persistent, severe hypoglycemia in different tumor types of mesochymal or epithelial origin; however, NICTH is infrequently induced by sarcomatoid carcinoma (SC). Despite some sarcomatoid and epithelioid characteristics in few cases of malignancies from epithelium, NICTH induced by recurrent SC in pelvic cavity in this report is extremely rare.
We report a case in which NICTH caused by recurrence and pulmonary metastases from SC in the pelvic cavity, and the computed tomography scan revealed multiple pelvic masses and multiple large masses in the pulmonary fields. During the treatment of intestinal obstruction, the patient presented paroxysmal loss of consciousness and sweating. Her glucose even reached 1.22 mmol/L while the serum glycosylated hemoglobin was normal and previous history of diabetes or use of oral hypoglycemic agents and insulin denied.
The laboratory examination showed that the low level of insulin, C-peptide, and growth hormone levels in the course of hypoglycemic episodes suggesting to the diagnosis of hypoglycemia induced by nonislet cell tumor, and the decreased levels of insulin-like growth factor (IGF)-I and IGFBP3 and the high expression of big IGF-II in the serum further confirmed the diagnosis of NICTH. Because of the widely pelvic recurrence and pulmonary metastases were unresected, the patient was discharged from the hospital after 2 weeks treatment with dexamethasone and glucose and unfortunately died 1 week later.
NICTH caused by SC in the pelvic cavity is extremely rare case in clinical. The aim of this report was to present the importance to examine big IGF-II expression in patient's serum in order to reach the diagnosis of NICTH in cases of intractable cancer-associated hypoglycemia.
doi:10.1097/MD.0000000000001577
PMCID: PMC4620829  PMID: 26496258
18.  SOX2 expression is associated with FGFR fusion genes and predicts favorable outcome in lung squamous cell carcinomas 
OncoTargets and therapy  2015;8:3009-3016.
Objectives
SOX2 is a gene that encodes for a transcription factor, which functions as an activator or suppressor of gene transcription. SOX2 amplification and overexpression have been found in various types of tumors and play important roles in cancer cells. The aim of the study was to evaluate SOX2 expression and amplification in lung squamous cell carcinomas (SCCs) and to determine the relationship with main clinicopathologic features, patient prognosis, and common driver mutations.
Materials and methods
SOX2 protein levels were measured by immunohistochemistry, while SOX2 copy numbers were measured by fluorescence in situ hybridization in resected samples from 162 Chinese lung SCC patients. All patients were also analyzed for mutations in EGFR, HER2, BRAF, PIK3CA, NFE2L2, and FGFR fusion genes. Clinical characteristics, including age, sex, smoking status, stage, relapse-free survival (RFS), and overall survival (OS), were collected.
Results
SOX2 overexpression and amplification were observed in 58.6% and 45.9% of lung SCCs. Lung SCC patients with SOX2 overexpression were significantly associated with absence of malignant tumor family history (P=0.021), FGFR fusion gene (P=0.046), longer RFS (P=0.041), and OS (P=0.025). No correlation was found between SOX2 gene amplification and main clinicopathologic features, patient prognosis, or common driver mutations.
Conclusion
SOX2 overexpression and amplification are common in lung SCCs. SOX2 over-expression was associated with FGFR fusion genes and predicted favorable outcome in lung SCCs. The underlying relationship of SOX2 and FGFR still needs further investigation.
doi:10.2147/OTT.S91293
PMCID: PMC4621178  PMID: 26527886
lung squamous cell carcinoma; SOX2 amplification; protein expression; FGFR fusion gene; prognostic marker
19.  Awakening from anesthesia using propofol or sevoflurane with epidural block in radical surgery for senile gastric cancer 
Objective: To study the awakening of the elderly patients from propofol intravenous general anesthesia or sevoflurane inhalation general anesthesia combined with epidural block after radical gastric cancer surgery. Method: Eighty cases receiving selective radical surgery for gastric cancer were included. They were aged 65-78 years and classified as ASA grade I-II. Using a random number table, the cases were divided into 4 groups (n = 20): propofol intravenous general anesthesia (P group), sevoflurane inhalation general anesthesia (S group), propofol intravenous general anesthesia combined with epidural block (PE group), and sevoflurane inhalation general anesthesia combined with epidural block (SE group). For P and PE group, target controlled infusion of propofol was performed; for S and SE group, sevoflurane was inhaled to induce and maintain general anesthesia; for PE and SE group, before general anesthesia induction, epidural puncture and catheterization at T7-8 was performed. After surgery, perform patient controlled intravenous analgesia (PCIA) or patient controlled epidural analgesia (PCEA), and maintain VAS ≤ 3. The recorded indicators were as follows: time to recovery of spontaneous respiration, time to awakening, time of endotracheal tube removal, time to orientation, time to achieve modified Aldrete scores ≥ 9, modified OAA/S and Aldrete scores upon endotracheal tube removal (T1), 5 min after removal (T2), 15 min after removal (T3) and 30 min after removal (T4), dose of intraoperative remifentanil, intraoperative hypotension, and emergence agitation. Results: Time to awakening, time of endotracheal tube removal, time to orientation, and time to achieve modified Aldrete scores ≥ 9 in PE and SE group were obviously shortened compared with P and S group (P < 0.05); modified OAA/S and Aldrete scores at T1 and T2 in PE and SE group were significantly higher than those in P and S group (P < 0.05), and the scores of SE group at T1 were much higher compared to PE group (P < 0.05). Dose of intraoperative remifentanil in PE and SE group was significantly lower than that in P and S group. Conclusion: Compared to propofol intravenous general anesthesia or sevoflurane inhalation general anesthesia, propofol or sevoflurane general anesthesia combined with epidural block was more conducive to increasing the awakening quality of the senile patients from anesthesia after radical gastric cancer surgery. Moreover, sevofluorane inhalation general anesthesia combined with epidural block achieved a more stable hemodynamics and a shortened time to awakening.
PMCID: PMC4694484  PMID: 26770584
Propofol; sevoflurane; epidural block; awakening; radical surgery for senile gastric cancer
20.  Development and characterization of 25 microsatellite primers for Ilex chinensis (Aquifoliaceae)1 
Applications in Plant Sciences  2015;3(10):apps.1500057.
Premise of the study:
To evaluate genetic variation and structure of Ilex chinensis (Aquifoliaceae), a dioecious evergreen tree, we developed 25 microsatellite markers from its nuclear genome.
Methods and Results:
Based on the biotin-streptavidin capture method, 10 polymorphic and 15 monomorphic microsatellite markers were developed. Ten polymorphic loci were characterized by 87 individuals sampled from three populations located in Zhejiang Province and Shanghai, China. The number of alleles per locus varied from two to 12. The observed and expected heterozygosities were 0.0435–0.9032 and 0.3121–0.8343, respectively.
Conclusions:
These microsatellite markers can be useful for further genetic studies of I. chinensis populations, and so contribute to forest restoration and management.
doi:10.3732/apps.1500057
PMCID: PMC4610312  PMID: 26504681
Aquifoliaceae; evergreen broadleaved forests; genetic diversity; genetic structure; Ilex chinensis; simple sequence repeat (SSR)
21.  The human disease network in terms of dysfunctional regulatory mechanisms 
Biology Direct  2015;10:60.
Background
Elucidation of human disease similarities has emerged as an active research area, which is highly relevant to etiology, disease classification, and drug repositioning. In pioneer studies, disease similarity was commonly estimated according to clinical manifestation. Subsequently, scientists started to investigate disease similarity based on gene-phenotype knowledge, which were inevitably biased to well-studied diseases. In recent years, estimating disease similarity according to transcriptomic behavior significantly enhances the probability of finding novel disease relationships, while the currently available studies usually mine expression data through differential expression analysis that has been considered to have little chance of unraveling dysfunctional regulatory relationships, the causal pathogenesis of diseases.
Methods
We developed a computational approach to measure human disease similarity based on expression data. Differential coexpression analysis, instead of differential expression analysis, was employed to calculate differential coexpression level of every gene for each disease, which was then summarized to the pathway level. Disease similarity was eventually calculated as the partial correlation coefficients of pathways’ differential coexpression values between any two diseases. The significance of disease relationships were evaluated by permutation test.
Results
Based on mRNA expression data and a differential coexpression analysis based method, we built a human disease network involving 1326 significant Disease-Disease links among 108 diseases. Compared with disease relationships captured by differential expression analysis based method, our disease links shared known disease genes and drugs more significantly. Some novel disease relationships were discovered, for example, Obesity and cancer, Obesity and Psoriasis, lung adenocarcinoma and S. pneumonia, which had been commonly regarded as unrelated to each other, but recently found to share similar molecular mechanisms. Additionally, it was found that both the type of disease and the type of affected tissue influenced the degree of disease similarity. A sub-network including Allergic asthma, Type 2 diabetes and Chronic kidney disease was extracted to demonstrate the exploration of their common pathogenesis.
Conclusion
The present study produces a global view of human diseasome for the first time from the viewpoint of regulation mechanisms, which therefore could provide insightful clues to etiology and pathogenesis, and help to perform drug repositioning and design novel therapeutic interventions.
Reviewers
This article was reviewed by Limsoon Wong, Rui Wang-Sattler, and Andrey Rzhetsky.
Electronic supplementary material
The online version of this article (doi:10.1186/s13062-015-0088-z) contains supplementary material, which is available to authorized users.
doi:10.1186/s13062-015-0088-z
PMCID: PMC4599653  PMID: 26450611
Human disease network; Disease similarity; Dysfunctional regulation mechanism; Differential coexpression analysis; Differential regulation analysis
22.  Effects of Soothing Liver and Invigorating Spleen Recipes on the IKKβ-NF-κB Signaling Pathway in Kupffer Cells of Nonalcoholic Steatohepatitis Rats 
This study investigates the effect of soothing liver and invigorating spleen recipes on steatohepatitis examining the IKKβ-NF-κB signaling pathway in KCs of NASH rats. SD male rats were randomly divided into 8 groups, and the NASH model was induced by a high-fat diet (HFD). After 26 weeks, liver tissue was examined in H&E stained sections and liver function was monitored biochemically. KCs were isolated by Seglen's method, with some modifications. The mRNA and protein expression of the IKKβ-NF-κB signaling pathway components was examined by quantitative PCR and Western blotting. The results show that the high-fat diet induced NASH in the rats, and the soothing liver recipe and invigorating spleen recipe decreased the levels of TNF-α, IL-1, and IL-6 in KCs, as well as inhibiting the mRNA and protein expression of the IKKβ-NF-κB signaling pathway components. In conclusion, the experiment indicated the importance of the IKKβ-NF-κB signaling pathway in KCs for the anti-inflammatory effects of the soothing liver and invigorating spleen recipes.
doi:10.1155/2015/687690
PMCID: PMC4609424  PMID: 26504479
23.  Reliability and Validity of the Chinese Version of FACIT-AI, a New Tool for Assessing Quality of Life in Patients with Malignant Ascites 
Journal of Palliative Medicine  2015;18(10):829-833.
Abstract
Objective: The study objective was to determine the reliability and validity of the Chinese version of the Functional Assessment of Chronic Illness Therapy – Ascites Index (FACIT-AI).
Methods: A forward-backward translation procedure was adopted to develop the Chinese version of the FACIT-AI, which was tested in 69 patients with malignant ascites. Cronbach's α, split-half reliability, and test-retest reliability were used to assess the reliability of the scale. The content validity index was used to assess the content validity, while factor analysis was used for construct validity and correlation analysis was used for criterion validity.
Results: The Cronbach's α was 0.772 for the total scale, and the split-half reliability was 0.693. The test-retest correlation was 0.972. The content validity index for the scale was 0.8–1.0. Four factors were extracted by factor analysis, and these contributed 63.51% of the total variance. Item-total correlations ranged from 0.591 to 0.897, and these were correlated with visual analog scale scores (correlation coefficient, 0.889; P<0.01).
Conclusions: The Chinese version of the FACIT-AI has good reliability and validity and can be used as a tool to measure quality of life in Chinese patients with malignant ascites.
doi:10.1089/jpm.2015.0061
PMCID: PMC4598917  PMID: 26177329
24.  MiR-23a sensitizes nasopharyngeal carcinoma to irradiation by targeting IL-8/Stat3 pathway 
Oncotarget  2015;6(29):28341-28356.
Radioresistance poses a major challenge in nasopharyngeal carcinoma (NPC) treatment, but little is known about how miRNA regulates this phenomenon. In this study, we investigated the function and mechanism of miR-23a in NPC radioresistance, one of downregulated miRNAs in the radioresistant NPC cells identified by our previous microarray analysis. We observed that miR-23a was frequently downregulated in the radioresistant NPC tissues, and its decrement correlated with NPC radioresistance and poor patient survival, and was an independent predictor for reduced patient survival. In vitro radioresponse assays showed that restoration of miR-23a expression markedly increased NPC cell radiosensitivity. In a mouse model, therapeutic administration of miR-23a agomir dramatically sensitized NPC xenografts to irradiation. Mechanistically, we found that reduced miR-23a promoted NPC cell radioresistance by activating IL-8/Stat3 signaling. Moreover, the levels of IL-8 and phospho-Stat3 were increased in the radioresistance NPC tissues, and negatively associated with miR-23a level. Our data demonstrate that miR-23a is a critical determinant of NPC radioresponse and prognostic predictor for NPC patients, and its decrement enhances NPC radioresistance through activating IL-8/Stat3 signaling, highlighting the therapeutic potential of miR-23a/IL-8/Stat3 signaling axis in NPC radiosensitization.
PMCID: PMC4695064  PMID: 26314966
nasopharyngeal carcinoma; radioresistance; miR-23a; IL-8; Stat3
25.  Prognostic value of Muc5AC in gastric cancer: A meta-analysis 
World Journal of Gastroenterology : WJG  2015;21(36):10453-10460.
AIM: To assess the correlation between decreased Muc5AC expression and patients’ survival and clinicopathological characteristics by conducting a meta-analysis.
METHODS: Literature searches were performed in PubMed and EMBASE, and 11 studies met our criteria. Summary hazard ratios or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the effect. For the pooled analysis of the correlation between decreased Muc5AC expression and clinicopathological characteristics (tumour invasion depth, lymph node metastasis, tumour-node-metastasis stage, tumour size, venous invasion and lymphatic invasion), ORs and their variance were combined to estimate the effect.
RESULTS: Eleven retrospective cohort studies comprising 2135 patients were included to assess the association between Muc5AC expression and overall survival and/or clinicopathological characteristics. Decreased Muc5AC expression was significantly correlated with poor overall survival of gastric cancer patients (pooled HR = 1.35, 95%CI: 1.08-1.7). Moreover, decreased Muc5AC expression was also significantly associated with tumour invasion depth (pooled OR = 2.12, 95%CI: 1.56-2.87) and lymph node metastasis (pooled OR = 1.56, 95%CI: 1.00-2.44) in gastric cancer.
CONCLUSION: Decreased Muc5AC expression might be a poor prognostic predictor for gastric cancer.
doi:10.3748/wjg.v21.i36.10453
PMCID: PMC4579892  PMID: 26420972
Prognosis; Muc5AC; Gastric cancer

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