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1.  Does carbon dioxide insufflation impact adenoma detection rate? A single-center retrospective analysis 
Endoscopy International Open  2016;4(12):E1275-E1279.
Background and study aims: Carbon dioxide (CO2) has been associated with reduced post-procedural pain and improved patient satisfaction when compared to air insufflation (AI). The effect of CO2 insufflation (CO2I) on the adenoma detection rate (ADR) remains unclear. The aims of this study are to compare ADR in patients undergoing screening colonoscopy with AI vs. CO2I and identify predictors of ADR.
Patients and methods: Single-center retrospective cohort study of 2,107 patients undergoing screening colonoscopy at the University of Florida Hospital between November 2011 and June 2015. Patient demographics, procedural parameters, and histology results were retrospectively obtained from a prospectively maintained colonoscopy database. Univariate and multivariate analysis were performed to identify predictors of ADR.
Results: A total of 2107 colonoscopies (644 with AI and 1463 with CO2I) were analyzed. Overall ADR was 27.8 %. There was no significant difference in ADR between AI (27.6 %) vs. CO2I (27.8 %) (P = 0.93). Method of insufflation (AI vs. CO2I) was not significantly associated with ADR (OR 0.9; 95 % CI:0.7 – 1.2). Older age (OR: 1.02; 95 % CI: 1.001 – 1.03 per year increase), male gender (OR 1.48; 95 % CI: 1.17 – 1.87), and longer scope withdraw time (OR 1.13; 95 % CI: 1.1 – 1.16 per minute) were associated with a higher ADR. Fellow involvement was negatively associated with ADR (OR 0.60; 95 % CI: 0.47 – 0.77).
Conclusion: ADR was similar between patients who underwent screening colonoscopy with AI vs. CO2I. While CO2I has been associated with improved patient comfort and post-procedural recovery time, there is no definitive evidence to suggest that this method of luminal distention enhances ADR.
PMCID: PMC5161121  PMID: 27995188
2.  Comparison of iris-fixated foldable lens and scleral-fixated foldable lens implantation in eyes with insufficient capsular support 
To compare the outcomes of vision using two different intraocular lens (IOL) replacement techniques, iris-fixated foldable intraocular lens (IF-IOL) and scleral-fixated foldable intraocular lens (SF-IOL) in patients with insufficient capsular support.
Total 63 eyes (62 patients) with insufficient posterior capsule support underwent replacement of IF-IOL or SF-IOL between January 2008 and August 2011. Outcome measures included changes in visual acuity, slit lamp examination, refractive indices and corneal curvatures.
The mean improvement of uncorrected visual acuity (UCVA) was greater in IF-IOL group compared to the SF-IOL group (0.43 D±0.19 D vs 0.35 D±0.18 D, P<0.05). Moreover, 12 (38.71%) eyes in IF-IOL group and 4 (12.50%) in SF-IOL group had a higher postoperative UCVA than preoperative best corrected visual acuity (BCVA) while 9 (29.03%) eyes in IF-IOL group and 18 (56.25%) in SF-IOL group had a lower postoperative UCVA than preoperative BCVA. The myopic mean manifest sphere and mean cylinder magnitude were lower in the IF-IOL group than that in the SF-IOL group (-0.47 D±0.58 D vs 0.50 D±0.43 D, P<0.01; 0.84 D±0.53 D vs 1.23 D±0.70 D, P<0.05). No difference of corneal astigmatism and surgically induced astigmatism was found between the two groups. In addition, fewer complications were observed in IF-IOL eyes.
IF-IOL implantation can give a significant improvement in vision with fewer complications than SF-IOL in patients with insufficient capsular support.
PMCID: PMC5145088  PMID: 27990363
iris-fixated foldable intraocular lens; scleral-fixated foldable intraocular lens; visual acuity; refraction
3.  Characterizing the Blood Oxygen Level-Dependent Fluctuations in Musculoskeletal Tumours Using Functional Magnetic Resonance Imaging 
Scientific Reports  2016;6:36522.
This study characterized the blood oxygen level-dependent (BOLD) fluctuations in benign and malignant musculoskeletal tumours via power spectrum analyses in pre-established low-frequency bands. BOLD MRI and T1-weighted imaging (T1WI) were collected for 52 patients with musculoskeletal tumours. Three ROIs were drawn on the T1WI image in the tumours’ central regions, peripheral regions and neighbouring tissue. The power spectrum of the BOLD within each ROI was calculated and divided into the following four frequency bands: 0.01–0.027 Hz, 0.027–0.073 Hz, 0.073–0.198 Hz, and 0.198–0.25 Hz. ANOVA was conducted for each frequency band with the following two factors: the location of the region of interest (LoR, three levels: tumour “centre”, “peripheral” and “healthy tissue”) and tumour characteristic (TC, two levels: “malignant” and “benign”). There was a significant main effect of LoR in the frequencies of 0.073–0.198 Hz and 0.198–0.25 Hz. These data were further processed with post-hoc pair-wise comparisons. BOLD fluctuations at 0.073–0.198 Hz were stronger in the peripheral than central regions of the malignant tumours; however, no such difference was observed for the benign tumours. Our findings provide evidence that the BOLD signal fluctuates with spatial heterogeneity in malignant musculoskeletal tumours at the frequency band of 0.073–0.198 Hz.
PMCID: PMC5109174  PMID: 27845359
4.  Transcriptional Repression of the VC2105 Protein by Vibrio FadR Suggests that It Is a New Auxiliary Member of the fad Regulon 
Recently, our group along with others reported that the Vibrio FadR regulatory protein is unusual in that, unlike the prototypical fadR product of Escherichia coli, which has only one ligand-binding site, Vibrio FadR has two ligand-binding sites and represents a new mechanism for fatty acid sensing. The promoter region of the vc2105 gene, encoding a putative thioesterase, was mapped, and a putative FadR-binding site (AA CTG GTA AGA GCA CTT) was proposed. Different versions of the FadR regulatory proteins were prepared and purified to homogeneity. Both electrophoretic mobility shift assay (EMSA) and surface plasmon resonance (SPR) determined the direct interaction of the vc2105 gene with FadR proteins of various origins. Further, EMSAs illustrated that the addition of long-chain acyl-coenzyme A (CoA) species efficiently dissociates the vc2105 promoter from the FadR regulator. The expression level of the Vibrio cholerae vc2105 gene was elevated 2- to 3-fold in a fadR null mutant strain, validating that FadR is a repressor for the vc2105 gene. The β-galactosidase activity of a vc2105-lacZ transcriptional fusion was increased over 2-fold upon supplementation of growth medium with oleic acid. Unlike the fadD gene, a member of the Vibrio fad regulon, the VC2105 protein played no role in bacterial growth and virulence-associated gene expression of ctxAB (cholera toxin A/B) and tcpA (toxin coregulated pilus A). Given that the transcriptional regulation of vc2105 fits the criteria for fatty acid degradation (fad) genes, we suggested that it is a new member of the Vibrio fad regulon.
IMPORTANCE The Vibrio FadR regulator is unusual in that it has two ligand-binding sites. Different versions of the FadR regulatory proteins were prepared and characterized in vitro and in vivo. An auxiliary fad gene (vc2105) from Vibrio was proposed that encodes a putative thioesterase and has a predicted FadR-binding site (AAC TGG TA A GAG CAC TT). The function of this putative binding site was proved using both EMSA and SPR. Further in vitro and in vivo experiments revealed that the Vibrio FadR is a repressor for the vc2105 gene. Unlike fadD, a member of the Vibrio fad regulon, VC2105 played no role in bacterial growth and expression of the two virulence-associated genes (ctxAB and tcpA). Therefore, since transcriptional regulation of vc2105 fits the criteria for fad genes, it seems likely that vc2105 acts as a new auxiliary member of the Vibrio fad regulon.
PMCID: PMC4836427  PMID: 26944841
5.  Prospective study of Helicobacter pylori antigens and gastric noncardia cancer risk in the Nutrition Intervention Trial cohort 
Helicobacter pylon (H. pylori) infection is the strongest known risk factor for gastric non-cardia adenocarcinoma (GNCA). We used multiplex serology to determine whether seropositivity to 15 H. pylori proteins is associated with the subsequent development of non-cardia gastric cancer in Linxian, China.
We included 448 GNCA cases and 1242 controls from two time-points within the Linxian General Population Nutrition Intervention Trial, Linxian. H. pylori multiplex seropositivity was defined as positivity to ≥4 of the 15 included antigens. Odds ratios (OR) and 95% confidence intervals were adjusted for major GNCA risk factors. Additionally, we undertook a meta-analysis combining H. pylori multiplex serology data from both timepoints.
H. pylori multiplex seropositivity was associated with a significant increase in risk of GNCA at one time-point (1985; OR: 3.44, 95% CI: 1.91, 6.19) and this association remained significant following adjustment for H. pylori or CagA ELISA seropositivity (OR: 2.92, 95% CI: 1.56, 5.47). Combining data from both timepoints in a meta-analysis H. pylori multiplex seropositivity was associated with an increased risk of GNCA, as were 6 individual antigens: GroEL, HP0305, CagA, VacA, HcpC and Omp. CagM was inversely associated with risk of GNCA.
We identified 6 individual antigens which confer an increase in risk of GNCA within this population of high H. pylori seroprevalence, as well as a single antigen which may be inversely associated with GNCA risk. We further determined that the H. pylori multiplex assay provides additional information to the conventional ELISA methods on risk of GNCA.
PMCID: PMC4529753  PMID: 25845708
Helicobacter pylori; multiplex serology; gastric cancer; esophageal cancer
6.  Controversies and evidence of hepatic resection for hepatocellular carcinoma☆ 
BBA Clinical  2016;6:125-130.
Symptoms of early hepatocellular carcinoma (HCC) often go unnoticed, so more than half of patients with primary HCC are diagnosed after their disease has already reached an intermediate or advanced stage, or after portal hypertension has appeared. While hepatic resection is widely recognized as a first-line therapy to treat very early or early HCC, its use in treating intermediate or advanced HCC or HCC involving portal hypertension remains controversial. Here we review PubMed-indexed literature covering the use of hepatic resection for such patients. The available evidence strongly suggests that, as a result of improvements in surgical techniques and perioperative care, hepatic resection can benefit many patients with intermediate or advanced HCC or with HCC associated with portal hypertension.
•This review summarized controversies and evidence of surgery for hepatocellular carcinoma (HCC) in the present.•Hepatic resection should be actively considered for selected patients with intermediate or advanced HCC or those combining with portal hypertension, with more favorable survival benefits.
PMCID: PMC5067978  PMID: 27761414
Hepatocellular carcinoma; Hepatectomy; The BCLC staging; Portal hypertension
7.  Disruption of cortical integration during midazolam‐induced light sedation 
Human Brain Mapping  2015;36(11):4247-4261.
This work examines the effect of midazolam‐induced light sedation on intrinsic functional connectivity of human brain, using a randomized, double‐blind, placebo‐controlled, cross‐over, within‐subject design. Fourteen healthy young subjects were enrolled and midazolam (0.03 mg/kg of the participant's body mass, to a maximum of 2.5 mg) or saline were administrated with an interval of one week. Resting‐state fMRI was conducted before and after administration for each subject. We focus on two types of networks: sensory related lower‐level functional networks and higher‐order functions related ones. Independent component analysis (ICA) was used to identify these resting‐state functional networks. We hypothesize that the sensory (visual, auditory, and sensorimotor) related networks will be intact under midazolam‐induced light sedation while the higher‐order (default mode, executive control, salience networks, etc.) networks will be functionally disconnected. It was found that the functional integrity of the lower‐level networks was maintained, while that of the higher‐level networks was significantly disrupted by light sedation. The within‐network connectivity of the two types of networks was differently affected in terms of direction and extent. These findings provide direct evidence that higher‐order cognitive functions including memory, attention, executive function, and language were impaired prior to lower‐level sensory responses during sedation. Our result also lends support to the information integration model of consciousness. Hum Brain Mapp 36:4247–4261, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
PMCID: PMC5049658  PMID: 26314702
resting‐state functional MRI (rs‐fMRI); independent component analysis (ICA); midazolam; sedation
8.  Danshensu alleviates cardiac ischaemia/reperfusion injury by inhibiting autophagy and apoptosis via activation of mTOR signalling 
The traditional Chinese medicine Danshensu (DSS) has a protective effect on cardiac ischaemia/reperfusion (I/R) injury. However, the molecular mechanisms underlying the DSS action remain undefined. We investigated the potential role of DSS in autophagy and apoptosis using cardiac I/R injury models of cardiomyocytes and isolated rat hearts. Cultured neonatal rat cardiomyocytes were subjected to 6 hrs of hypoxia followed by 18 hrs of reoxygenation to induce cell damage. The isolated rat hearts were used to perform global ischaemia for 30 min., followed by 60 min. reperfusion. Ischaemia/reperfusion injury decreased the haemodynamic parameters on cardiac function, damaged cardiomyocytes or even caused cell death. Pre‐treatment of DSS significantly improved cell survival and protected against I/R‐induced deterioration of cardiac function. The improved cell survival upon DSS treatment was associated with activation of mammalian target of rapamycin (mTOR) (as manifested by increased phosphorylation of S6K and S6), which was accompanied with attenuated autophagy flux and decreased expression of autophagy‐ and apoptosis‐related proteins (including p62, LC3‐II, Beclin‐1, Bax, and Caspase‐3) at both protein and mRNA levels. These results suggest that alleviation of cardiac I/R injury by pre‐treatment with DSS may be attributable to inhibiting excessive autophagy and apoptosis through mTOR activation.
PMCID: PMC5020629  PMID: 27385290
Danshensu; I/R injury; autophagy; apoptosis; mTOR
9.  Biodegradable black phosphorus-based nanospheres for in vivo photothermal cancer therapy 
Nature Communications  2016;7:12967.
Photothermal therapy (PTT) offers many advantages such as high efficiency and minimal invasiveness, but clinical adoption of PTT nanoagents have been stifled by unresolved concerns such as the biodegradability as well as long-term toxicity. Herein, poly (lactic-co-glycolic acid) (PLGA) loaded with black phosphorus quantum dots (BPQDs) is processed by an emulsion method to produce biodegradable BPQDs/PLGA nanospheres. The hydrophobic PLGA not only isolates the interior BPQDs from oxygen and water to enhance the photothermal stability, but also control the degradation rate of the BPQDs. The in vitro and in vivo experiments demonstrate that the BPQDs/PLGA nanospheres have inappreciable toxicity and good biocompatibility, and possess excellent PTT efficiency and tumour targeting ability as evidenced by highly efficient tumour ablation under near infrared (NIR) laser illumination. These BP-based nanospheres combine biodegradability and biocompatibility with high PTT efficiency, thus promising high clinical potential.
Black phosphorus is a biodegradable 2D material that has attracted growing interest in biomedicine. Here, the authors carry out in vitro and in vivo experiments to demonstrate that nanospheres loaded with black-phosphorus quantum dots perform as promising phothermal cancer therapy agents.
PMCID: PMC5056460  PMID: 27686999
10.  Association between abnormal default mode network activity and suicidality in depressed adolescents 
BMC Psychiatry  2016;16:337.
Suicide is the second leading cause of death among 15- to 29-year-olds in China, and 60 % of suicidal patients have a history of depression. Previous brain imaging studies have shown that depression and suicide may be associated with abnormal activity in default mode network (DMN) regions. However, no study has specifically investigated the relationship between DMN functional activity and suicidal behavior in depressed individuals. Therefore, in the present study, we directly investigated features of DMN brain activity in adolescent patients with histories of depression and attempted suicide.
A total of 35 sex- and age-matched suicidal depressed patients were compared with 18 non-suicidal depressed patients and 47 healthy controls. We explored functional activity changes in DMN regions that could be associated with suicidal behavior by comparing resting-state functional magnetic resonance imaging (rs-fMRI) signals using independent component analysis (ICA). Scores on six clinical scales that measure depression severity (Hamilton Depression Scale (HDRS) and Beck Depression Inventory (BDI)) and suicidal traits (Barratt Impulsiveness Scale (BIS-11), Suicide Attitude Questionnaire (SAQ), Beck Hopelessness Scale (BHS), and Scale for Suicide Ideation (SSI)) were compared in the three groups.
Compared with the healthy controls, all of the evaluated depressed patients showed increased functional connectivity in select DMN regions. The suicidal patients showed increased connectivity in the left cerebellum and decreased connectivity in the right posterior cingulate cortex (PCC), whereas the non-suicidal depressed patients showed increased connectivity in the left superior frontal gyrus, left lingual gyrus and right precuneus and decreased connectivity in the left cerebellum. Compared to the non-suicidal patients, the suicidal patients showed increased connectivity in the left cerebellum and the left lingual gyrus and decreased connectivity in the right precuneus. No differences in the scores of any clinical scales were found between the suicidal and non-suicidal depressed patients.
Collectively, our results highlight the importance of the DMN in the pathophysiology of depression and suggest that suicidal behavior in depressed adolescents may be related to abnormal functional connectivity in the DMN. In particular, abnormal connectivity in the PCC/precuneus and left cerebellum might be a predictor of suicidal behavior in depressed adolescent patients.
PMCID: PMC5041526  PMID: 27688124
Adolescents; Attempted suicide; Default mode network; Depression; rs-fMRI
11.  Fungal Endophytes as a Metabolic Fine-Tuning Regulator for Wine Grape 
PLoS ONE  2016;11(9):e0163186.
Endophytes proved to exert multiple effects on host plants, including growth promotion, stress resistance. However, whether endophytes have a role in metabolites shaping of grape has not been fully understood. Eight endophytic fungal strains which originally isolated from grapevines were re-inoculated to field-grown grapevines in this study, and their effects on both leaves and berries of grapevines at maturity stage were assessed, with special focused on secondary metabolites and antioxidant activities. High-density inoculation of all these endophytic fungal strains modified the physio-chemical status of grapevine to different degrees. Fungal inoculations promoted the content of reducing sugar (RS), total flavonoids (TF), total phenols (TPh), trans-resveratrol (Res) and activities of phenylalanine ammonia-lyase (PAL), in both leaves and berries of grapevine. Inoculation of endophytic fungal strains, CXB-11 (Nigrospora sp.) and CXC-13 (Fusarium sp.) conferred greater promotion effects in grape metabolic re-shaping, compared to other used fungal strains. Additionally, inoculation of different strains of fungal endophytes led to establish different metabolites patterns of wine grape. The work implies the possibility of using endophytic fungi as fine-tuning regulator to shape the quality and character of wine grape.
PMCID: PMC5033586  PMID: 27656886
12.  Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus 
Horne, Hisani N. | Chung, Charles C. | Zhang, Han | Yu, Kai | Prokunina-Olsson, Ludmila | Michailidou, Kyriaki | Bolla, Manjeet K. | Wang, Qin | Dennis, Joe | Hopper, John L. | Southey, Melissa C. | Schmidt, Marjanka K. | Broeks, Annegien | Muir, Kenneth | Lophatananon, Artitaya | Fasching, Peter A. | Beckmann, Matthias W. | Fletcher, Olivia | Johnson, Nichola | Sawyer, Elinor J. | Tomlinson, Ian | Burwinkel, Barbara | Marme, Frederik | Guénel, Pascal | Truong, Thérèse | Bojesen, Stig E. | Flyger, Henrik | Benitez, Javier | González-Neira, Anna | Anton-Culver, Hoda | Neuhausen, Susan L. | Brenner, Hermann | Arndt, Volker | Meindl, Alfons | Schmutzler, Rita K. | Brauch, Hiltrud | Hamann, Ute | Nevanlinna, Heli | Khan, Sofia | Matsuo, Keitaro | Iwata, Hiroji | Dörk, Thilo | Bogdanova, Natalia V. | Lindblom, Annika | Margolin, Sara | Mannermaa, Arto | Kosma, Veli-Matti | Chenevix-Trench, Georgia | Wu, Anna H. | ven den Berg, David | Smeets, Ann | Zhao, Hui | Chang-Claude, Jenny | Rudolph, Anja | Radice, Paolo | Barile, Monica | Couch, Fergus J. | Vachon, Celine | Giles, Graham G. | Milne, Roger L. | Haiman, Christopher A. | Marchand, Loic Le | Goldberg, Mark S. | Teo, Soo H. | Taib, Nur A. M. | Kristensen, Vessela | Borresen-Dale, Anne-Lise | Zheng, Wei | Shrubsole, Martha | Winqvist, Robert | Jukkola-Vuorinen, Arja | Andrulis, Irene L. | Knight, Julia A. | Devilee, Peter | Seynaeve, Caroline | García-Closas, Montserrat | Czene, Kamila | Darabi, Hatef | Hollestelle, Antoinette | Martens, John W. M. | Li, Jingmei | Lu, Wei | Shu, Xiao-Ou | Cox, Angela | Cross, Simon S. | Blot, William | Cai, Qiuyin | Shah, Mitul | Luccarini, Craig | Baynes, Caroline | Harrington, Patricia | Kang, Daehee | Choi, Ji-Yeob | Hartman, Mikael | Chia, Kee Seng | Kabisch, Maria | Torres, Diana | Jakubowska, Anna | Lubinski, Jan | Sangrajrang, Suleeporn | Brennan, Paul | Slager, Susan | Yannoukakos, Drakoulis | Shen, Chen-Yang | Hou, Ming-Feng | Swerdlow, Anthony | Orr, Nick | Simard, Jacques | Hall, Per | Pharoah, Paul D. P. | Easton, Douglas F. | Chanock, Stephen J. | Dunning, Alison M. | Figueroa, Jonine D.
PLoS ONE  2016;11(8):e0160316.
The Cancer Genetic Markers of Susceptibility genome-wide association study (GWAS) originally identified a single nucleotide polymorphism (SNP) rs11249433 at 1p11.2 associated with breast cancer risk. To fine-map this locus, we genotyped 92 SNPs in a 900kb region (120,505,799–121,481,132) flanking rs11249433 in 45,276 breast cancer cases and 48,998 controls of European, Asian and African ancestry from 50 studies in the Breast Cancer Association Consortium. Genotyping was done using iCOGS, a custom-built array. Due to the complicated nature of the region on chr1p11.2: 120,300,000–120,505,798, that lies near the centromere and contains seven duplicated genomic segments, we restricted analyses to 429 SNPs excluding the duplicated regions (42 genotyped and 387 imputed). Per-allelic associations with breast cancer risk were estimated using logistic regression models adjusting for study and ancestry-specific principal components. The strongest association observed was with the original identified index SNP rs11249433 (minor allele frequency (MAF) 0.402; per-allele odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.08–1.13, P = 1.49 x 10-21). The association for rs11249433 was limited to ER-positive breast cancers (test for heterogeneity P≤8.41 x 10-5). Additional analyses by other tumor characteristics showed stronger associations with moderately/well differentiated tumors and tumors of lobular histology. Although no significant eQTL associations were observed, in silico analyses showed that rs11249433 was located in a region that is likely a weak enhancer/promoter. Fine-mapping analysis of the 1p11.2 breast cancer susceptibility locus confirms this region to be limited to risk to cancers that are ER-positive.
PMCID: PMC4996485  PMID: 27556229
14.  Dynamically Tuning the Up-conversion Luminescence of Er3+/Yb3+ Co-doped Sodium Niobate Nano-crystals through Magnetic Field 
Scientific Reports  2016;6:31327.
In this work, we show here that the up-conversion luminescence of NaNbO3:Er3+/Yb3+ nano-materials can be modulated by magnetic field and a enhancement of up-conversion intensities by a factor of about 2 for Er3+:4S3/2 → 4I15/2 obtained at 30 T and about 5.4 for Er3+:4F9/2 → 4I15/2 obtained at 20 T. The increased up-conversion luminescence are mainly interpreted in terms of the enhanced non-radiation transition from 4I11/2 to 4I13/2 of Er3+ ions and the spin-orbital coupling (that is “mixing” effect) in crystal field by an external magnetic field. Meanwhile, we observed continuously spectra broadening with growing the magnetic field intensity, which is ascribed to the “mixing” effect induced by magnetic field and the difference of g factor of sub-bands. This bi-functional material with controllable optical-magnetic interactions has various potential applications, such as optical detection of magnetic field, etc.
PMCID: PMC4977560  PMID: 27502356
15.  Common genetic variants in epigenetic machinery genes and risk of upper gastrointestinal cancers 
Background: Populations in north central China are at high risk for oesophageal squamous cell carcinoma (ESCC) and gastric cancer (GC), and genetic variation in epigenetic machinery genes and pathways may contribute to this risk.
Methods: We used the adaptive multilocus joint test to analyse 192 epigenetic genes involved in chromatin remodelling, DNA methylation and microRNA biosynthesis in 1942 ESCC and 1758 GC cases [1126 cardia (GCA) and 632 non-cardia adenocarcinoma (GNCA)] and 2111 controls with Chinese ancestry. We examined potential function of risk alleles using in silico and expression quantitative trait loci (eQTLs) analyses.
Results: Suggestive pathway-based associations were observed for the overall epigenetic (P-valuePATH = 0.034) and chromatin remodelling (P-valuePATH = 0.039) pathways with risk of GCA, but not GC, GNCA or ESCC. Overall, 37 different epigenetic machinery genes were associated with risk of one or more upper gastrointestinal (UGI) cancer sites (P-valueGENE < 0.05), including 14 chromatin remodelling genes whose products are involved in the regulation of HOX genes. We identified a gastric eQTL (rs12724079; rho = 0.37; P = 0.0006) which regulates mRNA expression of ASH1L. Several suggestive eQTLs were also found in oesophageal (rs10898459 in EED), gastric cardia (rs7157322 in DICER1; rs8179271 in ASH1L), and gastric non-cardia (rs1790733 in PPP1CA) tissues.
Conclusions: Results of our analyses provide limited but suggestive evidence for a role of epigenetic gene variation in the aetiology of UGI cancer.
PMCID: PMC4598798  PMID: 25921222
Epigenetics; chromatin remodelling; DNA methylation; microRNA; oesophageal squamous cell carcinoma; gastric cancer; gastric cardia; gastric non-cardia; SNP; gene-based; pathway-based
16.  Clinical characteristics and one year outcomes in Chinese atrial fibrillation patients with stable coronary artery disease: a population-based study 
Atrial fibrillation (AF) and coronary artery disease (CAD) often coexist, however, the clinical characteristics and the impact of stable CAD on the outcomes in Chinese patients with AF has not been well understood.
Consecutive AF patients in 20 hospitals in China from November 2008 to October 2011 were enrolled. The primary endpoints included 1-year all-cause mortality, stroke, non-central nervous system (non-CNS) embolism, and major bleeding.
A total of 1947 AF patients were analyzed, of whom 40.5% had stable CAD. The mean CHADS2 scores in CAD patients were significantly higher than that of non-CAD patients (2.4 ± 1.4 vs. 1.4 ± 1.2, P < 0.001). During follow-up period, warfarin use is low in both groups, with relatively higher proportion in non-CAD patients compared with CAD patients (22.3% vs. 10.7%, P < 0.001). Compared with non-CAD patients, CAD patients had higher one-year all-cause mortality (16.8% vs. 12.9%, P = 0.017) and incidence of stroke (9.0% vs. 6.4%, P = 0.030), while the non-CNS embolism and major bleeding rates were comparable between the two groups. After multivariate adjustment, stable CAD was independently associated with increased risk of 1-year all-cause mortality (HR = 1.35, 95% CI: 1.01−1 .80, P = 0.040), but not associated with stroke (HR = 1.07, 95% CI: 0.72–1.58, P = 0.736).
Stable CAD was prevalent in Chinese AF patients and was independently associated with increased risk of 1-year all-cause mortality. Chinese AF patients with stable CAD received inadequate antithrombotic therapy and this grim status of antithrombotic therapy needed to be improved urgently.
PMCID: PMC5067427  PMID: 27781056
Antithrombotic therapy; Atrial fibrillation; CHADS2 score; Stable coronary artery disease
17.  Black phosphorus: a two-dimension saturable absorption material for mid-infrared Q-switched and mode-locked fiber lasers 
Scientific Reports  2016;6:30361.
Black phosphorus (BP) as a novel class of two-dimension (2D) materials has recently attracted enormous attention as a result of its unique physical and chemical features. The remarkably strong light-matter interaction and tunable direct band-gap at a wide range make it an ideal candidate especially in the mid-infrared wavelength region as the saturable absorber (SA). In this paper, the simple and effective liquid phase exfoliation (LPE) method was used to fabricate BP. By introducing the same BP SA into two specifically designed rare earth ions doped fluoride fiber lasers at mid-infrared wavebands, Q-switching with the pulse energy of 4.93 μJ and mode-locking with the pulse duration of 8.6 ps were obtained, respectively. The operation wavelength of ~2970 nm for generated pulse is the reported longest wavelength for BP SA based fiber lasers.
PMCID: PMC4960592  PMID: 27457338
19.  COX-2 promotes metastasis in nasopharyngeal carcinoma by mediating interactions between cancer cells and myeloid-derived suppressor cells 
Oncoimmunology  2015;4(11):e1044712.
The expansion of myeloid-derived suppressor cells (MDSCs) is a common feature of cancer, but its biological roles and molecular mechanism remain unclear. Here, we investigated a molecular link between MDSC expansion and tumor cell metastasis in nasopharyngeal carcinoma (NPC). We demonstrated that MDSCs expanded and were positively correlated with the elevated tumor COX-2 expression and serum IL-6 levels in NPC patients. Importantly, COX-2 and MDSCs were poor predictors of patient disease-free survival (DFS). Knocking down tumor COX-2 expression hampered functional TW03-mediated-MDSC cell (T-MDSC) induction with IL-6 blocking. We identified that T-MDSCs promoted NPC cell migration and invasion by triggering the epithelial-mesenchymal transition (EMT) on cell-to-cell contact, and T-MDSCs enhanced tumor experimental lung metastasis in vivo. Interestingly, the contact between T-MDSCs and NPC cells enhanced tumor COX-2 expression, which subsequently activated the β-catenin/TCF4 pathway, resulting in EMT of the cancer cells. Blocking transforming growth factor β (TGFβ) or inducible nitric oxide synthase (iNOS) significantly abolished the T-MDSC-induced upregulation of COX-2 and EMT scores in NPC cells, whereas the administration of TGFβ or L-arginine supplements upregulated COX-2 expression and EMT scores in NPC cells. These findings reveal that COX-2 is a key factor mediating the interaction between MDSCs and tumor cells, suggesting that the inhibition of COX-2 or MDSCs has the potential to suppress NPC metastasis.
PMCID: PMC4590030  PMID: 26451317
COX-2; myeloid-derived suppressor cells; nasopharyngeal carcinoma
20.  Polarization domain wall pulses in a microfiber-based topological insulator fiber laser 
Scientific Reports  2016;6:29128.
Topological insulators (TIs), are novel two-dimension materials, which can act as effective saturable absorbers (SAs) in a fiber laser. Moreover, based on the evanescent wave interaction, deposition of the TI on microfiber would create an effective SA, which has combined advantages from the strong nonlinear optical response in TI material together with the sufficiently-long-range interaction length in fiber taper. By using this type of TI SA, various scalar solitons have been obtained in fiber lasers. However, a single mode fiber always exhibits birefringence, and hence can support two orthogonal degenerate modes. Here we investigate experimentally the vector characters of a TI SA fiber laser. Using the saturated absorption and the high nonlinearity of the TI SA, a rich variety of dynamic states, including polarization-locked dark pulses and their harmonic mode locked counterparts, polarization-locked noise-like pulses and their harmonic mode locked counterparts, incoherently coupled polarization domain wall pulses, including bright square pulses, bright-dark pulse pairs, dark pulses and bright square pulse-dark pulse pairs are all observed with different pump powers and polarization states.
PMCID: PMC4933917  PMID: 27381942
21.  A Powerful Procedure for Pathway-Based Meta-analysis Using Summary Statistics Identifies 43 Pathways Associated with Type II Diabetes in European Populations 
PLoS Genetics  2016;12(6):e1006122.
Meta-analysis of multiple genome-wide association studies (GWAS) has become an effective approach for detecting single nucleotide polymorphism (SNP) associations with complex traits. However, it is difficult to integrate the readily accessible SNP-level summary statistics from a meta-analysis into more powerful multi-marker testing procedures, which generally require individual-level genetic data. We developed a general procedure called Summary based Adaptive Rank Truncated Product (sARTP) for conducting gene and pathway meta-analysis that uses only SNP-level summary statistics in combination with genotype correlation estimated from a panel of individual-level genetic data. We demonstrated the validity and power advantage of sARTP through empirical and simulated data. We conducted a comprehensive pathway-based meta-analysis with sARTP on type 2 diabetes (T2D) by integrating SNP-level summary statistics from two large studies consisting of 19,809 T2D cases and 111,181 controls with European ancestry. Among 4,713 candidate pathways from which genes in neighborhoods of 170 GWAS established T2D loci were excluded, we detected 43 T2D globally significant pathways (with Bonferroni corrected p-values < 0.05), which included the insulin signaling pathway and T2D pathway defined by KEGG, as well as the pathways defined according to specific gene expression patterns on pancreatic adenocarcinoma, hepatocellular carcinoma, and bladder carcinoma. Using summary data from 8 eastern Asian T2D GWAS with 6,952 cases and 11,865 controls, we showed 7 out of the 43 pathways identified in European populations remained to be significant in eastern Asians at the false discovery rate of 0.1. We created an R package and a web-based tool for sARTP with the capability to analyze pathways with thousands of genes and tens of thousands of SNPs.
Author Summary
As GWAS continue to grow in sample size, it is evident that these studies need to be utilized more effectively for detecting individual susceptibility variants, and more importantly, to provide insight into global genetic architecture of complex traits. Towards this goal, identifying association with respect to a collection of variants in biological pathways can be particularly insightful for understanding how networks of genes might be affecting pathophysiology of diseases. Here we present a new pathway analysis procedure that can be conducted using summary-level association statistics, which have become the main vehicle for performing meta-analysis of individual genetic variants across studies in large consortia. Through simulation studies we showed the proposed method was more powerful than the existing state-of-art method. We carried out a comprehensive pathway analysis of 4,713 candidate pathways on their association with T2D using two large studies with European ancestry and identified 43 T2D-associated pathways. Further examinations of those 43 pathways in 8 Asian studies showed that some pathways were trans-ethnically associated with T2D. This analysis clearly highlights novel T2D-associated pathways beyond what has been known from single-variant association analysis reported from largest GWAS to date. We also identify a novel locus for T2D in the European populations at chromosome 17q21 (rs1058018, p = 3.06 × 10−8).
PMCID: PMC4928884  PMID: 27362418
22.  Is the Best Evidence Good Enough: Quality Assessment and Factor Analysis of Meta-Analyses on Depression 
PLoS ONE  2016;11(6):e0157808.
The quality of meta-analyses (MAs) on depression remains uninvestigated.
To assess the overall reporting and methodological qualities of MAs on depression and to explore potential factors influencing both qualities.
MAs investigating epidemiology and interventions for depression published in the most recent year (2014–2015) were selected from PubMed, EMBASE, PsycINFO and Cochrane Library. The characteristics of the included studies were collected and the total and per-item quality scores of the included studies were calculated based on the two checklists. Univariate and multivariate linear regression analyses were used to explore the potential factors influencing the quality of the articles.
A total of 217 MAs from 74 peer-reviewed journals were included. The mean score of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was 23.0 of 27 and mean score of Assessment of Multiple Systematic Reviews (AMSTAR) was 8.3 of 11. Items assessing registration and protocol (14.2%, 37/217) in PRISMA and item requiring a full list of included and excluded studies (16.1%, 40/217) in AMSTAR had poorer adherences than other items. The MAs that included only RCTs, pre-registered, had five more authors or authors from Cochrane groups and the MAs found negative results had better reporting and methodological qualities.
The reporting and methodological qualities of MAs on depression remained to be improved. Design of included studies, characteristics of authors and pre-registration in PROSPERO database are important factors influencing quality of MAs in the field of depression.
PMCID: PMC4919061  PMID: 27336624
23.  Evaluation of Volatile Organic Compounds and Carbonyl Compounds Present in the Cabins of Newly Produced, Medium- and Large-Size Coaches in China 
An air-conditioned coach is an important form of transportation in modern motorized society; as a result, there is an increasing concern of in-vehicle air pollution. In this study, we aimed to identify and quantify the levels of volatile organic compounds (VOCs) and carbonyl compounds (CCs) in air samples collected from the cabins of newly produced, medium- and large-size coaches. Among the identified VOCs and CCs, toluene, ethylbenzene, xylene, formaldehyde, acetaldehyde, acrolein/acetone, and isovaleraldehyde were relatively abundant in the cabins. Time was found to affect the emissions of the contaminants in the coaches. Except for benzaldehyde, valeraldehyde and benzene, the highest in-vehicle concentrations of VOCs and CCs were observed on the 15th day after coming off the assembly line, and the concentrations exhibited an approximately inverted U-shaped pattern as a function of time. Interestingly, this study also showed that the interior temperature of the coaches significantly affected the VOCs emissions from the interior materials, whereas the levels of CCs were mainly influenced by the relative humidity within the coaches. In China, guidelines and regulations for the in-vehicle air quality assessment of the coaches have not yet been issued. The results of this study provide further understanding of the in-vehicle air quality of air-conditioned coaches and can be used in the development of both specific and general rules regarding medium- and large-size coaches.
PMCID: PMC4924053  PMID: 27314375
volatile organic compounds (VOCs); carbonyl compounds (CCs); coach; in-vehicle; temperature; humidity
24.  Meter-long multiblock copolymer microfibers via interfacial bioorthogonal polymerization 
High molecular weight multiblock copolymers are synthesized as robust polymer fibers via interfacial bioorthogonal polymerization employing the rapid cycloaddition of s-tetrazines with strained trans-cyclooctenes. When cell-adhesive peptide was incorporated in the tetrazine monomer, the resulting protein-mimetic polymer fibers provide guidance cues for cell attachment and elongation.
PMCID: PMC4423755  PMID: 25824805
multiblock copolymer; interfacial polymerization; bioorthogonal; fibers; guidance cues

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