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2.  The impact of inhibitory mechanisms in the inner retina on spatial tuning of RGCs 
Scientific Reports  2016;6:21966.
Spatial tuning properties of retinal ganglion cells (RGCs) are sharpened by lateral inhibition originating at both the outer and inner plexiform layers. Lateral inhibition in the retina contributes to local contrast enhancement and sharpens edges. In this study, we used dynamic clamp recordings to examine the contribution of inner plexiform inhibition, originating from spiking amacrine cells, to the spatial tuning of RGCs. This was achieved by injecting currents generated from physiologically recorded excitatory and inhibitory stimulus-evoked conductances, into different types of primate and mouse RGCs. We determined the effects of injections of size-dependent conductances in which presynaptic inhibition and/or direct inhibition onto RGCs were partly removed by blocking the activity of spiking amacrine cells. We found that inhibition originating from spiking amacrine cells onto bipolar cell terminals and onto RGCs, work together to sharpen the spatial tuning of RGCs. Furthermore, direct inhibition is crucial for preventing spike generation at stimulus offset. These results reveal how inhibitory mechanisms in the inner plexiform layer contribute to determining size tuning and provide specificity to stimulus polarity.
doi:10.1038/srep21966
PMCID: PMC4764933  PMID: 26905860
3.  Increases in Lifestyle Activities as a Result of Experience Corps® Participation 
Experience Corps® (EC) was designed to simultaneously increase cognitive, social, and physical activity through high-intensity volunteerism in elementary school classrooms. It is, therefore, highly likely that EC participation may alter pre-existing patterns of lifestyle activity. This study examined the impact of “real-world” volunteer engagement on the frequency of participation in various lifestyle activities over a 2-year period. Specifically, we examined intervention-related changes on reported activity levels at 12 and 24 months post-baseline using Intention-to-Treat (ITT) and Complier Average Causal Effect (CACE) analyses, which account for the amount of program exposure. ITT analyses indicated that, compared to the control group, EC participants reported modest increases (approximately half a day/month) in overall activity level, especially in intellectual and physical activities 12 months post-baseline. Increases in activity were not found at the 24-month assessment. CACE models revealed similar findings for overall activity as well as for intellectual and physical activities at 12 months. Additionally, CACE findings suggested modest increases in social activity at 12 months and in intellectual and passive activities at 24 months post-baseline. This community-based, health promotion intervention has the potential to impact lifestyle activity, which may lead to long-term increases in activity and to other positive cognitive, physical, and psychosocial health outcomes.
doi:10.1007/s11524-014-9918-z
PMCID: PMC4338117  PMID: 25378282
Lifestyle; Engagement; Activities; Older adults; Volunteers
4.  Histone acetyltransferase PCAF regulates inflammatory molecules in the development of renal injury 
Epigenetics  2015;10(1):62-71.
Kidney diseases, including chronic kidney disease (CKD) and acute kidney injury (AKI), are associated with inflammation. The mechanism that regulates inflammation in these renal injuries remains unclear. Here, we demonstrated that p300/CBP-associated factor (PCAF), a histone acetyltransferase, was overexpressed in the kidneys of db/db mice and lipopolysaccharide (LPS)-injected mice. Moreover, elevated histone acetylation, such as H3K18ac, and up-regulation of some inflammatory genes, such as ICAM-1, VCAM-1, and MCP-1, were found upon these renal injuries. Furthermore, increased H3K18ac was recruited to the promoters of ICAM-1, VCAM-1, and MCP-1 in the kidneys of LPS-injected mice. In vitro studies demonstrated that PCAF knockdown in human renal proximal tubule epithelial cells (HK-2) led to downregulation of inflammatory molecules, including VCAM-1, ICAM-1, p50 subunit of NF-κB (p50), and MCP-1 mRNA and protein levels, together with significantly decreased H3K18ac level. Consistent with these, overexpression of PCAF enhanced the expression of inflammatory molecules. Furthermore, PCAF deficiency reduced palmitate-induced recruitment of H3K18ac on the promoters of ICAM-1 and MCP-1, as well as inhibited palmitate-induced upregulation of these inflammatory molecules. In summary, the present work demonstrates that PCAF plays an essential role in the regulation of inflammatory molecules through H3K18ac, which provides a potential therapeutic target for inflammation-related renal diseases.
doi:10.4161/15592294.2014.990780
PMCID: PMC4622516  PMID: 25496441
acute kidney injury; diabetic nephropathy; histone acetylations; inflammation; PCAF
5.  Cdk1 orders mitotic events through coordination of a chromosome-associated phosphatase switch 
Nature Communications  2015;6:10215.
RepoMan is a scaffold for signalling by mitotic phosphatases at the chromosomes. During (pro)metaphase, RepoMan-associated protein phosphatases PP1 and PP2A-B56 regulate the chromosome targeting of Aurora-B kinase and RepoMan, respectively. Here we show that this task division is critically dependent on the phosphorylation of RepoMan by protein kinase Cyclin-dependent kinase 1 (Cdk1), which reduces the binding of PP1 but facilitates the recruitment of PP2A-B56. The inactivation of Cdk1 in early anaphase reverses this phosphatase switch, resulting in the accumulation of PP1-RepoMan to a level that is sufficient to catalyse its own chromosome targeting in a PP2A-independent and irreversible manner. Bulk-targeted PP1-RepoMan also inactivates Aurora B and initiates nuclear-envelope reassembly through dephosphorylation-mediated recruitment of Importin β. Bypassing the Cdk1 regulation of PP1-RepoMan causes the premature dephosphorylation of its mitotic-exit substrates in prometaphase. Hence, the regulation of RepoMan-associated phosphatases by Cdk1 is essential for the timely dephosphorylation of their mitotic substrates.
RepoMan is a signalling scaffold for mitotic phosphatases PP1 and PP2A-B56, which regulate targeting of Aurora B and RepoMan respectively, to the chromosomes. Here Qian et al. show that Cdk1 phosphorylates RepoMan to modulate the binding of PP1 and PP2A-B56, contributing to orderly mitotic progression.
doi:10.1038/ncomms10215
PMCID: PMC4703885  PMID: 26674376
6.  Prognostic nomogram integrated systemic inflammation score for patients with esophageal squamouscell carcinoma undergoing radical esophagectomy 
Scientific Reports  2015;5:18811.
Growing evidence indicates that nomogram combined with the biomarkers of systemic inflammation response could provide more accurate prediction than conventional staging systems in tumors. This study aimed to establish an effective prognostic nomogram for resectable thoracic esophageal squamouscell carcinoma (ESCC) based on the clinicopathological parameters and inflammation-based prognostic scores. We retrospectively investigated 916 ESCC patients who underwent radical esophagectomy. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve, and compared with the 6th and 7th AJCC TNM classifications. The neutrophil lymphocyte ratio (NLR), C-reactive protein albumin (CRP/Alb) ratio, histological grade, T stage and modified N stage were integrated in the nomogram. The C-index of the nomogram for predicting the survival was 0.72, which showed better predictive ability of OS than the 6th or 7th TNM stages in the primary cohort (P < 0.001). The calibration curve showed high consistency between the nomogram and actual observation. The decision curve analysis showed more potential of clinical application of the prediction models compared with TNM staging system. Moreover, our findings were supported by the validation cohort. The proposed nomogram showed more accurate prognostic prediction for patients with ESCC after radical esophagectomy.
doi:10.1038/srep18811
PMCID: PMC4686940  PMID: 26689680
7.  Comparison of simple vs. performance-based fall prediction models: data from the National Health and Aging Trends Study 
Gerontology & geriatric medicine  2015;1:2333721415584850.
OBJECTIVE
To compare the predictive ability of standard falls prediction models based on physical performance assessments with more parsimonious prediction models based on self-reported data.
DESIGN
We developed a series of fall prediction models progressing in complexity and compared area under the receiver operating characteristic curve (AUC) across models.
SETTING
National Health and Aging Trends Study (NHATS), which surveyed a nationally-representative sample of Medicare enrollees (age ≥65) at baseline (Round 1: 2011–12) and one-year follow-up (Round 2: 2012–3).
PARTICIPANTS
6056 community-dwelling individuals who participated in Rounds 1 and 2 of NHATS.
MEASUREMENTS
Primary outcomes were one-year incidence of “any fall” and “recurrent falls”. Prediction models were compared and validated in development and validation sets, respectively.
RESULTS
A prediction model that included demographic information, self-reported problems with balance and coordination, and previous fall history was the most parsimonious model that optimized AUC for both any fall (AUC=0.69, 95% CI 0.67–0.71) and recurrent falls (AUC=0.77, 95% CI 0.74–0.79) in the development set. Physical performance testing provided marginal additional predictive value.
CONCLUSION
A simple clinical prediction model that does not include physical performance testing could facilitate routine, widespread falls risk screening in the ambulatory care setting.
doi:10.1177/2333721415584850
PMCID: PMC4686273  PMID: 26702410
Falls; fall risk; recurrent falls
8.  Updated experiences with minimally invasive McKeown esophagectomy for esophageal cancer 
World Journal of Gastroenterology  2015;21(45):12873-12881.
AIM: To update our experiences with minimally invasive McKeown esophagectomy for esophageal cancer.
METHODS: We retrospectively reviewed the medical records of 445 consecutive patients who underwent minimally invasive McKeown esophagectomy between January 2009 and July 2015 at the Cancer Hospital of Chinese Academy of Medical Sciences and used 103 patients who underwent open McKeown esophagectomy in the same period as controls. Among 375 patients who underwent total minimally invasive McKeown esophagectomy, 180 in the early period were chosen for the study of learning curve of total minimally invasive McKeown esophagectomy. These 180 minimally invasive McKeown esophagectomies performed by five surgeons were divided into three groups according to time sequence as group 1 (n = 60), group 2 (n = 60) and group 3 (n = 60).
RESULTS: Patients who underwent total minimally invasive McKeown esophagectomy had significantly less intraoperative blood loss than patients who underwent hybrid minimally invasive McKeown esophagectomy or open McKeown esophagectomy (100 mL vs 300 mL vs 200 mL, P = 0.001). However, there were no significant differences in operation time, number of harvested lymph nodes, or postoperative morbidity including incidence of pulmonary complication and anastomotic leak between total minimally invasive McKeown esophagectomy, hybrid minimally invasive McKeown esophagectomy and open McKeown esophagectomy groups. There were no significant differences in 5-year survival between these three groups (60.5% vs 47.9% vs 35.6%, P = 0.735). Patients in group 1 had significantly longer duration of operation than those in groups 2 and 3. There were no significant differences in intraoperative blood loss, number of harvested lymph nodes, or postoperative morbidity including incidence of pulmonary complication and anastomotic leak between groups 1, 2 and 3.
CONCLUSION: Total minimally invasive McKeown esophagectomy was associated with reduced intraoperative blood loss and comparable short term and long term survival compared with hybrid minimally invasive McKeown esophagectomy or open Mckeown esophagectomy. At least 12 cases are needed to master total minimally invasive McKeown esophagectomy in a high volume center.
doi:10.3748/wjg.v21.i45.12873
PMCID: PMC4671043  PMID: 26668512
Surgical procedures; Minimally invasive; Esophagectomy; Outcome; Learning curve
9.  Factors Mediating the Effects of a Depression Intervention on Functional Disability in Older African Americans 
Background/Objectives
Determine factors mediating the effects of a depression intervention for older African Americans on functional disability; and secondarily, if functional improvements mediated intervention effects on depressive symptoms.
Design
Structural equation modeling to examine mediators in a secondary analysis of a randomized trial with 4-month follow-up
Setting
Community-dwelling population in Philadelphia region
Participants
208 African Americans (≥55) with depressive symptoms living in an urban area
Intervention
Up to 10, one-hour sessions over 4 months conducted by licensed social workers who provided care management, referral/linkages, stress reduction techniques, depression knowledge and symptom recognition and behavioral activation techniques.
Measurements
Main outcome was self-reported functional difficulty level for 18 basic activities. Mediators included depression severity (PHQ-9), depression knowledge/symptom recognition, behavioral activation and state anxiety.
Results
At 4-months, compared to controls, the intervention had positive effects on functional difficulty and all mediators (ps< .0001). Separate structural equation models indicated the intervention’s impact on functional disability was significantly mediated by two factors, reduced depressive symptoms (23.5% mediated) and improved depression knowledge/symptom recognition (52.9% mediated). Enhancing behavioral activation and decreasing anxiety were not found to mediate improvements in functional disability. The two significant mediators jointly explained 62.5% of the intervention’s total effect on functional disability. Functional improvement was not found to mediate the intervention’s impact on depressive symptoms.
Conclusion
This multi-component depression intervention for African Americans has an impact on functional disability that is driven primarily by enhancing symptom recognition and decreasing depressive symptoms. Reduction of functional difficulties however did not account for improvements in depressive symptoms. Nonpharmacologic treatments for depressive symptoms that enhance symptom recognition in older African Americans can also reduce their functional difficulties with daily living activities.
doi:10.1111/jgs.13156
PMCID: PMC4415989  PMID: 25516024
Depression; functional disability; mediation analysis
10.  Clinical evaluation of prostate cancer gene 3 score in diagnosis among Chinese men with prostate cancer and benign prostatic hyperplasia 
BMC Urology  2015;15:118.
Background
Prostate cancer is the second most common diagnosed cancer in men. Due to the low specificity of current diagnosis methods for detecting prostate cancer, identification of new biomarkers is highly desirable. The study was conducted to determine the clinical utility of the prostate cancer gene 3 (PCA3) assay to predict biopsy-detected cancers in Chinese men.
Methods
The study included men who had a biopsy at The Affiliated Sixth People’s Hospital of Shanghai Jiao Tong University from January 2013 to December 2013. Formalin-fixed, paraffin-embedded tissue blocks were used to test PCA3 and prostate-specific antigen (PSA) mRNA. The diagnostic accuracy of the PCA3 score for predicting a positive biopsy outcome was studied using sensitivity and specificity, and it was compared with PSA.
Results
The probability of a positive biopsy increased with increasing PCA3 scores. The mean PCA3 score was significantly higher in men with prostate cancer (198.03, 95 % confidence interval [CI] 74.79–321.27) vs benign prostatic hyperplasia (BPH) (84.31, 95 % CI 6.47–162.15, P < 0.01). The PCA3 score (cutoff 35) had a sensitivity of 85.7 % and specificity of 62.5 %. Receiver operating characteristic analysis showed higher areas under the ROC curve for the PCA3 score vs PSA, but without statistical significance.
Conclusions
Increased PCA3 in biopsy tissue correlated with prostate cancer and the PCA3 assay may improve the diagnosis efficacy as the PCA3 score being independent of PSA level. The diagnostic significance of urinary PCA3 testing should be explored in future study to determine the prediction value in guiding biopsy decision as the clinical relevance of current study was limited for PCA3 testing based on biopsy tissue in a limited number of Chinese men.
doi:10.1186/s12894-015-0110-x
PMCID: PMC4666051  PMID: 26628213
Prostate cancer; Prostate cancer gene 3; Prostate-specific antigen; China
11.  HMGB1 in Health and Disease 
Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed High-Mobility Group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors, thus has cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. Indeed, a number of emergent strategies have been used to inhibit HMGB1 expression, release, and activity in vitro and in vivo. These include antibodies, peptide inhbitiors, RNAi, anti-coagulants, endogenous hormones, various chemical compounds, HMGB1-receptor and signaling pathway inhibition, artificial DNAs, physical strategies including vagus nerve stimulation and other surgical approaches. Future work further investigating the details of HMGB1 localizationtion, structure, post-translational modification, and identifccation of additional partners will undoubtedly uncover additional secrets regarding HMGB1’s multiple functions.
doi:10.1016/j.mam.2014.05.001
PMCID: PMC4254084  PMID: 25010388
12.  Uniportal versus three-port video-assisted thoracoscopic surgery for spontaneous pneumothorax: a meta-analysis 
Journal of Thoracic Disease  2015;7(12):2274-2287.
Background
Whether or not uniportal video-assisted thoracoscopic surgery (VATS) is beneficial for spontaneous pneumothorax remains inconclusive. This meta-analysis aimed to summarize the available evidence to assess the feasibility and advantages of uniportal VATS for the treatment of spontaneous pneumothorax compared with three-port VATS.
Methods
Eligible publications were identified by searching the Cochrane Library, PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data databases and CQVIP. Odds ratios (OR) and standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated to compare dichotomous and continuous variables, respectively.
Results
This meta-analysis was based on 17 studies and included a total of 988 patients with spontaneous pneumothorax. No death was reported during the perioperative period. Compared with three-port VATS groups, there was a statistically significant difference in uniportal VATS groups regarding postoperative hospital stay (SMD= −0.58; 95% CI: −1.04 to −0.12; P=0.01), paresthesia (OR=0.13; 95% CI: 0.07 to 0.24; P<0.00001), visual analogue pain score (VAS) at 24 hours (h) (SMD= −0.87; 95% CI: −1.07 to −0.68; P<0.00001), VAS at 72 h (SMD= −0.49; 95% CI: −0.68 to −0.30; P<0.00001), and patients satisfaction scale (PSS) at 24 h (SMD= −0.81; 95% CI: −1.21 to −0.41; P<0.0001), PSS at 48 h (SMD= −0.69; 95% CI: −1.08 to −0.29; P=0.0007). However there was no statistically significant difference on the recurrence (OR=0.79; 95% CI: 0.42 to 1.46; P=0.45), operative time (SMD= −0.23; 95% CI: −0.21 to 0.67; P=0.31), length of postoperative drainage (SMD= −0.17; 95% CI: −0.40 to −0.07; P=0.16), VAS at 48 h (SMD= −0.40; 95% CI: −1.47 to 0.67; P=0.46), and PSS at 72 h (SMD= −0.13; 95% CI: −0.52 to −0.25; P=0.50).
Conclusions
The results for mortality, recurrence, operative time, and length of postoperative drainage were similar between uniportal and three-port VATS. Uniportal VATS resulted in reduction in postoperative pain and paresthesia as well as an improvement in patients’ satisfaction. This meta-analysis indicated that using uniportal VATS to treat spontaneous pneumothorax was safe and feasible, and it may be a better alternative procedure because of its advantage in reducing postoperative pain and paresthesia.
doi:10.3978/j.issn.2072-1439.2015.12.56
PMCID: PMC4703656  PMID: 26793349
Uniportal; three-port surgery; video-assisted thoracoscopic surgery (VATS); spontaneous pneumothorax; meta-analysis
13.  Histopathological findings in a critically ill patient with avian influenza A (H7N9) 
Journal of Thoracic Disease  2015;7(12):E672-E677.
To date, data regarding the pulmonary histopathology of human H7N9 disease are scarce. We herein describe a patient with a severe case of avian influenza A (H7N9). A chest computerized tomography (CT) scan showed diffuse ground-glass opacities and consolidation throughout the lungs. A resection of pulmonary bullae in the right middle lobe was performed by video-assisted thoracic surgery (VATS) based on the extracorporeal membrane oxygenation (ECMO) supportive technique on the 23rd day after the onset of symptoms because of a right pneumothorax persistent air leak. The histopathological findings of the resected lung tissue revealed pneumocyte hyperplasia and fibroproliferative changes along with diffuse alveolar damage. Bronchoalveolar lavage fluid (BALF) specimens for influenza A (H7N9) virus were continuously positive for more than three weeks, despite oseltamivir treatment, and continuous viral replication significantly prolonged the course of the disease. The patient’s clinical status continuously deteriorated, with the development of refractory hypoxemia due to progressive and rapid lung fibrosis, which was confirmed by the final histological changes observed from a limited post-mortem biopsy of lung tissue. Pre-terminally, he developed multi-organ failure and died on the 39th day after symptom onset, despite corticosteroid treatment.
doi:10.3978/j.issn.2072-1439.2015.11.59
PMCID: PMC4703663  PMID: 26793388
Influenza virus; avian; H7N9; histopathology; oseltamivir; pneumonia
14.  Posttranslational modification of autophagy-related proteins in macroautophagy 
Autophagy  2014;11(1):28-45.
Macroautophagy is an intracellular catabolic process involved in the formation of multiple membrane structures ranging from phagophores to autophagosomes and autolysosomes. Dysfunction of macroautophagy is implicated in both physiological and pathological conditions. To date, 38 autophagy-related (ATG) genes have been identified as controlling these complicated membrane dynamics during macroautophagy in yeast; approximately half of these genes are clearly conserved up to human, and there are additional genes whose products function in autophagy in higher eukaryotes that are not found in yeast. The function of the ATG proteins, in particular their ability to interact with a number of macroautophagic regulators, is modulated by posttranslational modifications (PTMs) such as phosphorylation, glycosylation, ubiquitination, acetylation, lipidation, and proteolysis. In this review, we summarize our current knowledge of the role of ATG protein PTMs and their functional relevance in macroautophagy. Unraveling how these PTMs regulate ATG protein function during macroautophagy will not only reveal fundamental mechanistic insights into the regulatory process, but also provide new therapeutic targets for the treatment of autophagy-associated diseases.
doi:10.4161/15548627.2014.984267
PMCID: PMC4502723  PMID: 25484070
autophagy; autophagy-related proteins; posttranslational modification; AMPK, AMP-activated protein kinase; ATG, autophagy-related; MTORC1, mechanistic target of rapamycin complex 1; PE, phosphatidylethanolamine; PTM, posttranslational modification; Ub, ubiquitin; Ubl, ubiquitin like
15.  Vitrified/warmed single blastocyst transfer in preimplantation genetic diagnosis/preimplantation genetic screening cycles 
Objective: To investigate the single blastocyst transfer in preimplantation genetic diagnosis (PGD)/preimplantation genetic screening (PGS) cycles. Methods: 80 PGD/PGS cycles undergoing blastocyst biopsy were studied. There were 88 warming cycles during the study period. Only one warmed blastocyst was transferred per cycle. The outcomes were followed up to the infants were born. Results: The embryo implantation rate was 54.55% (48/88). The clinical pregnancy rate was 54.55% (48/88) per transfer cycle and 60% (48/80) per initial PGD/PGS cycle. There was no multi-pregnant in this study. The live birth rate was 42.05% (37/88) per transfer cycle and 46.25% (37/80) per initial PGD/PGS cycle. Conclusion: In PGD/PGS cycles, single blastocyst transfer reduces the multiple pregnancy rate without affecting the clinical outcomes.
PMCID: PMC4723957  PMID: 26885112
Preimplantation genetic diagnosis/preimplantation genetic screening; single blastocyst transfer; multiple births; vitrification
16.  Direct Conversion of CH3NH3PbI3 from Electrodeposited PbO for Highly Efficient Planar Perovskite Solar Cells 
Scientific Reports  2015;5:15889.
Organic-inorganic hybrid perovskite materials have recently been identified as a promising light absorber for solar cells. In the efficient solar cells, the perovskite active layer has generally been fabricated by either vapor deposition or two-step sequential deposition process. Herein, electrochemically deposited PbO film is in situ converted into CH3NH3PbI3 through solid-state reaction with adjacent CH3NH3I layer, exhibiting a large-scale flat and uniform thin film with fully substrate coverage. The resultant planar heterojunction photovoltaic device yields a best power conversion efficiency of 14.59% and an average power conversion efficiency of 13.12 ± 1.08% under standard AM 1.5 conditions. This technique affords a facile and environment-friendly method for the fabrication of the perovskite based solar cells with high reproducibility, paving the way for the practical application.
doi:10.1038/srep15889
PMCID: PMC4625132  PMID: 26510520
17.  MiR-373 drives the epithelial-to-mesenchymal transition and metastasis via the miR-373-TXNIP-HIF1α-TWIST signaling axis in breast cancer 
Oncotarget  2015;6(32):32701-32712.
Our previous proteomics study revealed that thioredoxin-interacting protein (TXNIP) was down-regulated by miR-373. However, little is known of the mechanism by which miR-373 decreases TXNIP to stimulate metastasis. In this study, we show that miR-373 promotes the epithelial-to-mesenchymal transition (EMT) in breast cancer. MiR-373 suppresses TXNIP by binding to the 3′UTR of TXNIP, which in turn, induces cancer cell EMT and metastasis. TXNIP co-expression, but not the TXNIP-3′UTR, reverses the enhancement of EMT, migration, invasion and metastasis induced by miR-373. MiR-373 stimulates EMT, migration and invasion through TXNIP-dependent reactive oxygen species (ROS) reduction. Mechanistically, miR-373 up-regulates and activates the HIF1α-TWIST signaling axis via the TXNIP pathway. Consequently, TWIST induces miR-373 expression by binding to the promoter of the miR-371-373 cluster. Clinically, miR-373 is negatively associated with TXNIP and positively associated with HIF1α and TWIST, and activation of the miR-373-TXNIP-HIF1α-TWIST signaling axis is correlated with a worse outcome in patients with breast cancer. This signaling axis may be an independent prognostic factor for patients with breast cancer.
PMCID: PMC4741723  PMID: 26196741
miR-373; EMT; TXNIP; ROS; TWIST
18.  HBx-related long non-coding RNA DBH-AS1 promotes cell proliferation and survival by activating MAPK signaling in hepatocellular carcinoma 
Oncotarget  2015;6(32):33791-33804.
Accumulating evidence supports an important role for the hepatitis B virus x protein (HBx) in the pathogenesis of hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC), but the underlying mechanisms are not entirely clear. Here, we identified a novel long noncoding RNA (lncRNA) DBH-AS1 involved in the HBx-mediated hepatocarcinogenesis. The levels of DBH-AS1 were positively correlated with hepatitis B surface antigen (HBsAg) and tumor size in HCC tissues. Functionally, transgenic expression of DBH-AS1 significantly enhanced cell proliferation and tumorigenesis, whereas short hairpin RNA knockdown of DBH-AS1 caused an inhibition of cell proliferation. Mechanistically, overexpression of DBH-AS1 induced cell cycle progression by accelerating G1/S and G2/M transition concomitantly with upregulation of CDK6, CCND1, CCNE1 and downregulation of p16, p21 and p27. We also found that enhanced DBH-AS1 expression inhibited serum starvation-induced apoptosis of HCC cells. In contrast, suppressed DBH-AS1 expression had opposite effects. Furthermore, DBH-AS1 was shown to activate MAPK pathway. We also provide evidence that DBH-AS1 could be significantly induced by HBx protein and markedly down-regulated by p53. Thus, we concluded that DBH-AS1 can be induced by HBx and inactivated by p53, and consequently promote cell proliferation and cell survival through activation of MAPK signaling in HCC. Our study suggests that DBH-AS1 acts as an oncogene for HCC.
PMCID: PMC4741803  PMID: 26393879
lncRNA; DBH-AS1; HCC; proliferation; HBx
19.  Progress in the treatment of pulmonary metastases after liver transplantation for hepatocellular carcinoma 
World Journal of Hepatology  2015;7(20):2309-2314.
Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, and is the third leading cause of cancer-related death. Liver transplantation (LT) has become a curative treatment for patients with HCC. However, recurrence and metastasis after LT are the main factors reducing long-term survival in patients, and the lung is the most common site of metastasis after LT for HCC, although metastasis to liver, para-aortic lymph nodes and renal periphery are observed. Thus, the treatment of pulmonary metastases after LT for HCC has become a hot research topic, the successful treatment of pulmonary metastases can significantly prolong the survival of LT patients. Although single conventional treatment (chemotherapy, surgery and external beam radiation therapy), immunosuppression, image-guided minimally invasive therapy (radiofrequency ablation, microwave ablation, cryoablation, and brachytherapy) and molecular targeted drugs have had a significant effect, patients do not have durable remission and the long-term survival rate is disappointing. Therefore, improving existing treatments and identifying a more effective combination therapy are important research issues in the prevention and treatment of pulmonary metastases after LT for HCC. The paper reviewed single conventional treatments, new treatments, and combination therapy, to provide a basis for the best treatment of these patients.
doi:10.4254/wjh.v7.i20.2309
PMCID: PMC4568491  PMID: 26380655
Liver transplantation; Progress; Treatment; Pulmonary metastases; Hepatocellular carcinoma
20.  EST-based in silico identification and in vitro test of antimicrobial peptides in Brassica napus 
BMC Genomics  2015;16(1):653.
Background
Brassica napus is the third leading source of vegetable oil in the world after soybean and oil palm. The accumulation of gene sequences, especially expressed sequence tags (ESTs) from plant cDNA libraries, has provided a rich resource for genes discovery including potential antimicrobial peptides (AMPs). In this study, we used ESTs including those generated from B. napus cDNA libraries of seeds, pathogen-challenged leaves and deposited in the public databases, as a model, to perform in silico identification and consequently in vitro confirmation of putative AMP activities through a highly efficient system of recombinant AMP prokaryotic expression.
Results
In total, 35,788 were generated from cDNA libraries of pathogen-challenged leaves and 187,272 ESTs from seeds of B. napus, and the 644,998 ESTs of B. napus were downloaded from the EST database of PlantGDB. They formed 201,200 unigenes. First, all the known AMPs from the AMP databank (APD2 database) were individually queried against all the unigenes using the BLASTX program. A total of 972 unigenes that matched the 27 known AMP sequences in APD2 database were extracted and annotated using Blast2GO program. Among these unigenes, 237 unigenes from B. napus pathogen-challenged leaves had the highest ratio (1.15 %) in this unigene dataset, which is 13 times that of the unigene datasets of B. napus seeds (0.09 %) and 2.3 times that of the public EST dataset. About 87 % of each EST library was lipid-transfer protein (LTP) (32 % of total unigenes), defensin, histone, endochitinase, and gibberellin-regulated proteins. The most abundant unigenes in the leaf library were endochitinase and defensin, and LTP and histone in the pub EST library. After masking of the repeat sequence, 606 peptides that were orthologous matched to different AMP families were found. The phylogeny and conserved structural motifs of seven AMPs families were also analysed. To investigate the antimicrobial activities of the predicted peptides, 31 potential AMP genes belonging to different AMP families were selected to test their antimicrobial activities after bioinformatics identification. The AMP genes were all optimized according to Escherichia coli codon usage and synthetized through one-step polymerase chain reaction method. The results showed that 28 recombinant AMPs displayed expected antimicrobial activities against E. coli and Micrococcus luteus and Sclerotinia sclerotiorum strains.
Conclusion
The study not only significantly expanded the number of known/predicted peptides, but also contributed to long-term plant genetic improvement for increased resistance to diverse pathogens of B.napus. These results proved that the high-throughput method developed that combined an in silico procedure with a recombinant AMP prokaryotic expression system is considerably efficient for identification of new AMPs from genome or EST sequence databases.
Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1849-x) contains supplementary material, which is available to authorized users.
doi:10.1186/s12864-015-1849-x
PMCID: PMC4557752  PMID: 26330304
Expressed sequence tag; Antimicrobial peptides; Antimicrobial activities; Brassica napus; In silico identification; Highly efficient AMP prokaryotic expression system
21.  The Influence of Sleep Disruption and Pain Perception on Indicators of Quality of Life in Individuals Living with Dementia at Home 
This cross-sectional study evaluated the influence of sleep quality and pain perceptions on different dimensions of quality of life in community-dwelling persons with dementia. Evaluations of pain were collected using Visual Analog Scale (VAS), sleep disruption using Pittsburg Sleep Quality Index (PSQI) items, and quality of life indicators using the DemQOL-Proxy in 88 persons with dementia and their family caregivers. Lower overall quality of life was associated with the presence of pain and symptoms of sleep disruption when controlling for mental status, age, and number of health conditions. Pain and sleep symptoms were differentially associated with different aspects of QoL. As symptoms negatively impact quality of life but are modifiable, better clinical procedures are needed to prevent and also identify and treat symptoms of pain and sleep disturbance in community-dwelling persons with dementia.
doi:10.1016/j.gerinurse.2014.08.005
PMCID: PMC4416487  PMID: 25193739
quality of life; caregiving; sleep disturbance; pain; dementia
22.  Mediators of the Impact of a Home-based Intervention (Beat the Blues) on Depressive Symptoms among Older African Americansa 
Psychology and aging  2014;29(3):601-611.
Older African Americans (N=208) with depressive symptoms were randomly assigned to a home-based nonpharmacologic intervention (Beat the Blues, BTB) or wait-list control group. BTB was delivered by licensed social workers and involved up to 10 home visits focused on care management, referral and linkage, depression knowledge and efficacy in symptom recognition, instruction in stress reduction techniques, and behavioral activation through identification of personal goals and action plans for achieving them. Structured interviews by assessors masked to study assignment were used to assess changes in depressive symptoms (main trial endpoint), behavioral activation, depression knowledge, formal care service utilization and anxiety (mediators) at baseline and 4-months. At 4-months, the intervention had a positive effect on depressive symptoms and all mediators except formal care service utilization. Structural equation models indicated that increased activation, enhanced depression knowledge, and decreased anxiety each independently mediated a significant proportion of the intervention’s impact on depressive symptoms as assessed with two different measures (PHQ-9 and CES-D). These three factors also jointly explained over 60% of the intervention’s total effect on both indicators of depressive symptoms. Our findings suggest that most of the impact of BTB on depressive symptoms is driven by enhancing activation or becoming active, reducing anxiety, and improving depression knowledge/efficacy. The intervention components appear to work in concert and may be mutually necessary for maximal benefits from treatment to occur. Implications for designing tailored interventions to address depressive symptoms among older African Americans are discussed.
doi:10.1037/a0036784
PMCID: PMC4176772  PMID: 25244479
depression; mediation models; mental health disparities
23.  Prognostic Significance of Premature Atrial Complexes Burden in Prediction of Long-Term Outcome 
Background
The prognostic significance of premature atrial complex (PAC) burden is not fully elucidated. We aimed to investigate the relationship between the burden of PACs and long-term outcome.
Methods and Results
We investigated the clinical characteristics of 5371 consecutive patients without atrial fibrillation (AF) or a permanent pacemaker (PPM) at baseline who underwent 24-hour electrocardiography monitoring between January 1, 2002, and December 31, 2004. Clinical event data were retrieved from the Bureau of National Health Insurance of Taiwan. During a mean follow-up duration of 10±1 years, there were 1209 deaths, 1166 cardiovascular-related hospitalizations, 3104 hospitalizations for any reason, 418 cases of new-onset AF, and 132 PPM implantations. The optimal cut-off of PAC burden for predicting mortality was 76 beats per day, with a sensitivity of 63.1% and a specificity of 63.5%. In multivariate analysis, a PAC burden >76 beats per day was an independent predictor of mortality (hazard ratio: 1.384, 95% CI: 1.230 to 1.558), cardiovascular hospitalization (hazard ratio: 1.284, 95% CI: 1.137 to 1.451), new-onset AF (hazard ratio: 1.757, 95% CI: 1.427 to 2.163), and PPM implantation (hazard ratio: 2.821, 95% CI: 1.898 to 4.192). Patients with frequent PAC had increased risk of mortality attributable to myocardial infarction, heart failure, and sudden cardiac death. Frequent PACs increased risk of PPM implantation owing to sick sinus syndrome, high-degree atrioventricular block, and/or AF.
Conclusions
The burden of PACs is independently associated with mortality, cardiovascular hospitalization, new-onset AF, and PPM implantation in the long term.
doi:10.1161/JAHA.115.002192
PMCID: PMC4599506  PMID: 26316525
atrial fibrillation; permanent pacemaker; premature atrial complex; sick sinus syndrome
24.  Analysis of the correlation between P53 and Cox-2 expression and prognosis in esophageal cancer 
Oncology Letters  2015;10(4):2197-2203.
The present study aimed to explore the importance of P53 and Cox-2 protein expression in esophageal cancer and assess their influence on prognosis. The expression of P53 and Cox-2 was assessed in esophageal cancer samples from 195 patients subjected to radical surgery at Changzhou First People's Hospital (Changzhou, China) between May 2010 and December 2011. Expression of P53 and Cox-2 proteins were detected in 60.5% (118/195) and 69.7% (136/195) of the samples, respectively, and were co-expressed in 43.1% (84/195) of the samples. A correlation was identified between P53 expression and overall survival (OS) (P=0.0351) as well as disease-free survival (DFS) (P=0.0307). In addition, the co-expression of P53 and Cox-2 also correlated with OS (P=0.0040) and DFS (P=0.0042). P53 expression (P=0.023), TNM staging (P<0.001) and P53/Cox-2 co-expression (P=0.009) were identified as independent factors affecting OS in patients with esophageal cancer via a Cox multivariate regression model analysis. A similar analysis also identified P53 expression (P=0.020), TNM staging (P<0.001) and P53/Cox-2 co-expression (P=0.008) as independent prognostic factors influencing DFS in these patients. Binary logistic regression analysis demonstrated a correlation between P53 expression (P=0.012), TNM staging (P<0.001), tumor differentiation level (P=0.023) and P53/Cox-2 co-expression (P=0.021), and local recurrence or distant esophageal cancer metastasis. The results of the present study indicate that P53 and Cox-2 proteins may act synergistically in the development of esophageal cancer, and the assessment of P53/Cox-2 co-expression status in esophageal cancer biopsies may become an important diagnostic criterion to evaluate the prognosis of patients with esophageal cancer.
doi:10.3892/ol.2015.3624
PMCID: PMC4579898  PMID: 26622818
esophageal cancer; P53; Cox-2; relevance; prognosis
25.  Finite element analysis of the stability of combined plate internal fixation in posterior wall fractures of acetabulum 
Objective: This study aims to explore the mechanical stability of combined plate internal fixation in posterior wall fractures of the acetabulum. Methods: The fracture and internal fixation models were established in this study and they were divided into four kinds of internal fixation models, finite element analysis was performed. The four groups were 2 mini-plates and 1 reconstruction plate fixation (A), Reconstruction plate internal fixation group (B), 2 screws internal fixation group (C) and mini-plates internal fixation group (D). The displacement of each node was measured and evaluated. Results: There was no distortion in the geometric shape of the finite element model. The results of stress showed that it was less in the anterior pelvic ring and distributed uniform in labrum acetabulare; the stress was bigger in the upper and middle of sacroiliac joint and sciatic notch in sitting position. Conclusions: Combined plate internal fixation for posterior wall fractures of acetabular were stable and reliable, it is better than the other three methods.
PMCID: PMC4612957  PMID: 26550272
Finite element; posterior wall; acetabular fracture; mini-plate

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