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author:("Liu, weibei")
1.  SGK1 inhibition induces autophagy-dependent apoptosis via the mTOR-Foxo3a pathway 
British Journal of Cancer  2017;117(8):1139-1153.
Background:
Although inhibition of SGK1 has been shown to delay cancer progression, the underlying mechanisms have not yet been elucidated.
Methods:
We investigated the cellular responses to GSK650394 treatment and SGK1 silencing (or overexpression) in human prostate cancer (PCa) cell lines and PC3 xenografts by flow cytometry, western blotting, immunofluorescence, transmission electron microscopy and immunohistochemistry.
Results:
In the present study, we demonstrated that SGK1 inhibition, mediated by either GSK650394 or SGK1 shRNA, induced G2/M arrest, apoptosis and autophagy. Furthermore, 3MA-mediated autophagy inhibition attenuated SGK1 inhibition-induced apoptosis, suggesting that induction of autophagy precedes apoptosis. Moreover, ectopic expression of SGK1 significantly attenuated the GSK650394-induced effects. Suppression of mTOR and Foxo3a phosphorylation is critical for blockade of SGK1-induced autophagy and apoptosis, at least partially via pFoxo3a (S253)-LC3 and pFoxo3a (S253)-p27 interactions. Dual inhibition of mTOR and SGK1 enhances autophagy activation and leads to synergistic cytocidal effects in PCa cells.
Conclusions:
In summary, our findings show that SGK1 inhibition exhibits significant antitumour effects against PCa in vitro and in vivo. This study uncovered a novel mechanism of SGK1 inhibition in PCa, which is mediated, at least in part, by inducing autophagy-dependent apoptosis via the mTOR-Foxo3a pathway.
doi:10.1038/bjc.2017.293
PMCID: PMC5674106  PMID: 29017179
prostate cancer; SGK1; autophagy; apoptosis; cell cycle arrest
2.  Proceedings of the 14th annual conference of INEBRIA 
Holloway, Aisha S. | Ferguson, Jennifer | Landale, Sarah | Cariola, Laura | Newbury-Birch, Dorothy | Flynn, Amy | Knight, John R. | Sherritt, Lon | Harris, Sion K. | O’Donnell, Amy J. | Kaner, Eileen | Hanratty, Barbara | Loree, Amy M. | Yonkers, Kimberly A. | Ondersma, Steven J. | Gilstead-Hayden, Kate | Martino, Steve | Adam, Angeline | Schwartz, Robert P. | Wu, Li-Tzy | Subramaniam, Geetha | Sharma, Gaurav | McNeely, Jennifer | Berman, Anne H. | Kolaas, Karoline | Petersén, Elisabeth | Bendtsen, Preben | Hedman, Erik | Linderoth, Catharina | Müssener, Ulrika | Sinadinovic, Kristina | Spak, Fredrik | Gremyr, Ida | Thurang, Anna | Mitchell, Ann M. | Finnell, Deborah | Savage, Christine L. | Mahmoud, Khadejah F. | Riordan, Benjamin C. | Conner, Tamlin S. | Flett, Jayde A. M. | Scarf, Damian | McRee, Bonnie | Vendetti, Janice | Gallucci, Karen Steinberg | Robaina, Kate | Clark, Brendan J. | Jones, Jacqueline | Reed, Kathryne D. | Hodapp, Rachel M. | Douglas, Ivor | Burnham, Ellen L. | Aagaard, Laura | Cook, Paul F. | Harris, Brett R. | Yu, Jiang | Wolff, Margaret | Rogers, Meighan | Barbosa, Carolina | Wedehase, Brendan J. | Dunlap, Laura J. | Mitchell, Shannon G. | Dusek, Kristi A. | Gryczynski, Jan | Kirk, Arethusa S. | Oros, Marla T. | Hosler, Colleen | O’Grady, Kevin E. | Brown, Barry S. | Angus, Colin | Sherborne, Sidney | Gillespie, Duncan | Meier, Petra | Brennan, Alan | de Vargas, Divane | Soares, Janaina | Castelblanco, Donna | Doran, Kelly M. | Wittman, Ian | Shelley, Donna | Rotrosen, John | Gelberg, Lillian | Edelman, E. Jennifer | Maisto, Stephen A. | Hansen, Nathan B. | Cutter, Christopher J. | Deng, Yanhong | Dziura, James | Fiellin, Lynn E. | O’Connor, Patrick G. | Bedimo, Roger | Gibert, Cynthia | Marconi, Vincent C. | Rimland, David | Rodriguez-Barradas, Maria C. | Simberkoff, Michael S. | Justice, Amy C. | Bryant, Kendall J. | Fiellin, David A. | Giles, Emma L. | Coulton, Simon | Deluca, Paolo | Drummond, Colin | Howel, Denise | McColl, Elaine | McGovern, Ruth | Scott, Stephanie | Stamp, Elaine | Sumnall, Harry | Vale, Luke | Alabani, Viviana | Atkinson, Amanda | Boniface, Sadie | Frankham, Jo | Gilvarry, Eilish | Hendrie, Nadine | Howe, Nicola | McGeechan, Grant J. | Ramsey, Amy | Stanley, Grant | Clephane, Justine | Gardiner, David | Holmes, John | Martin, Neil | Shevills, Colin | Soutar, Melanie | Chi, Felicia W. | Weisner, Constance | Ross, Thekla B. | Mertens, Jennifer | Sterling, Stacy A. | Shorter, Gillian W. | Heather, Nick | Bray, Jeremy | Cohen, Hildie A. | McPherson, Tracy L. | Adam, Cyrille | López-Pelayo, Hugo | Gual, Antoni | Segura-Garcia, Lidia | Colom, Joan | Ornelas, India J. | Doyle, Suzanne | Donovan, Dennis | Duran, Bonnie | Torres, Vanessa | Gaume, Jacques | Grazioli, Véronique | Fortini, Cristiana | Paroz, Sophie | Bertholet, Nicolas | Daeppen, Jean-Bernard | Satterfield, Jason M. | Gregorich, Steven | Alvarado, Nicholas J. | Muñoz, Ricardo | Kulieva, Gozel | Vijayaraghavan, Maya | Adam, Angéline | Cunningham, John A. | Díaz, Estela | Palacio-Vieira, Jorge | Godinho, Alexandra | Kushir, Vladyslav | O’Brien, Kimberly H. M. | Aguinaldo, Laika D. | Sellers, Christina M. | Spirito, Anthony | Chang, Grace | Blake-Lamb, Tiffany | LaFave, Lea R. Ayers | Thies, Kathleen M. | Pepin, Amy L. | Sprangers, Kara E. | Bradley, Martha | Jorgensen, Shasta | Catano, Nico A. | Murray, Adelaide R. | Schachter, Deborah | Andersen, Ronald M. | Rey, Guillermina Natera | Vahidi, Mani | Rico, Melvin W. | Baumeister, Sebastian E. | Johansson, Magnus | Sinadinovic, Christina | Hermansson, Ulric | Andreasson, Sven | O’Grady, Megan A. | Kapoor, Sandeep | Akkari, Cherine | Bernal, Camila | Pappacena, Kristen | Morley, Jeanne | Auerbach, Mark | Neighbors, Charles J. | Kwon, Nancy | Conigliaro, Joseph | Morgenstern, Jon | Magill, Molly | Apodaca, Timothy R. | Borsari, Brian | Hoadley, Ariel | Scott Tonigan, J. | Moyers, Theresa | Fitzgerald, Niamh M. | Schölin, Lisa | Barticevic, Nicolas | Zuzulich, Soledad | Poblete, Fernando | Norambuena, Pablo | Sacco, Paul | Ting, Laura | Beaulieu, Michele | Wallace, Paul George | Andrews, Matthew | Daley, Kate | Shenker, Don | Gallagher, Louise | Watson, Rod | Weaver, Tim | Bruguera, Pol | Oliveras, Clara | Gavotti, Carolina | Barrio, Pablo | Braddick, Fleur | Miquel, Laia | Suárez, Montse | Bruguera, Carla | Brown, Richard L. | Capell, Julie Whelan | Paul Moberg, D. | Maslowsky, Julie | Saunders, Laura A. | McCormack, Ryan P. | Scheidell, Joy | Gonzalez, Mirelis | Bauroth, Sabrina | Liu, Weiwei | Lindsay, Dawn L. | Lincoln, Piper | Hagle, Holly | Wallhed Finn, Sara | Hammarberg, Anders | Andréasson, Sven | King, Sarah E. | Vargo, Rachael | Kameg, Brayden N. | Acquavita, Shauna P. | Van Loon, Ruth Anne | Smith, Rachel | Brehm, Bonnie J. | Diers, Tiffiny | Kim, Karissa | Barker, Andrea | Jones, Ashley L. | Skinner, Asheley C. | Hinman, Agatha | Svikis, Dace S. | Thacker, Casey L. | Resnicow, Ken | Beatty, Jessica R. | Janisse, James | Puder, Karoline | Bakshi, Ann-Sofie | Milward, Joanna M. | Kimergard, Andreas | Garnett, Claire V. | Crane, David | Brown, Jamie | West, Robert | Michie, Susan | Rosendahl, Ingvar | Andersson, Claes | Gajecki, Mikael | Blankers, Matthijs | Donoghue, Kim | Lynch, Ellen | Maconochie, Ian | Phillips, Ceri | Pockett, Rhys | Phillips, Tom | Patton, R. | Russell, Ian | Strang, John | Stewart, Maureen T. | Quinn, Amity E. | Brolin, Mary | Evans, Brooke | Horgan, Constance M. | Liu, Junqing | McCree, Fern | Kanovsky, Doug | Oberlander, Tyler | Zhang, Huan | Hamlin, Ben | Saunders, Robert | Barton, Mary B. | Scholle, Sarah H. | Santora, Patricia | Bhatt, Chirag | Ahmed, Kazi | Hodgkin, Dominic | Gao, Wenwu | Merrick, Elizabeth L. | Drebing, Charles E. | Larson, Mary Jo | Sharma, Monica | Petry, Nancy M. | Saitz, Richard | Weisner, Constance M. | Young-Wolff, Kelly C. | Lu, Wendy Y. | Blosnich, John R. | Lehavot, Keren | Glass, Joseph E. | Williams, Emily C. | Bensley, Kara M. | Chan, Gary | Dombrowski, Julie | Fortney, John | Rubinsky, Anna D. | Lapham, Gwen T. | Forray, Ariadna | Olmstead, Todd A. | Gilstad-Hayden, Kathryn | Kershaw, Trace | Dillon, Pamela | Weaver, Michael F. | Grekin, Emily R. | Ellis, Jennifer D. | McGoron, Lucy | McGoron, Lucy
doi:10.1186/s13722-017-0087-8
PMCID: PMC5606215
3.  Neuromodulation of courtship drive through tyramine-responsive neurons in the Drosophila brain 
Current biology : CB  2016;26(17):2246-2256.
SUMMARY
Neuromodulators influence the activities of collections of neurons, and have profound impacts on animal behavior. Male courtship drive is complex, and is subject to neuromodulatory control. Using the fruit fly, Drosophila melanogaster, we identified neurons in the brain (inferior posterior slope; IPS) that impact courtship drive, and were controlled by tyramine—a biogenic amine related to dopamine, whose roles in most animals are enigmatic. We knocked out a tyramine-specific receptor, TyrR, which was expressed in IPS neurons. Loss of TyrR led to a striking elevation in courtship activity between males. This effect occurred only in the absence of females, as the TyrRGal4 mutant males exhibited a wild-type preference for females. Artificial hyperactivation of IPS neurons caused a large increase in male-male courtship, while suppression of IPS activity decreased male-female courtship. We conclude that TyrR is a receptor for tyramine, and suggest that it serves to curb high levels of courtship activity through functioning as an inhibitory neuromodulator.
doi:10.1016/j.cub.2016.06.061
PMCID: PMC5021585  PMID: 27498566
4.  Androgen-independent LNCaP cells are a subline of LNCaP cells with a more aggressive phenotype and androgen suppresses their growth by inducing cell cycle arrest at the G1 phase 
Androgen deprivation therapy (ADT, surgical or chemical castration) is the mainstay treatment for metastatic prostate cancer (PCa); however, patients ineluctably relapse despite extremely low androgen levels. This evolution of PCa indicates its lethal progression. In this study, to mimic the traits of clinical PCa progression in vitro, we investigated the alterations in the cell biological characteristics in androgen-independent LNCaP cells (LNCaP-AI cells) compared with LNCaP cells. We also examined the effects of androgen on LNCaP and LNCaP-AI cell proliferation, androgen receptor (AR) expression and prostate-specific antigen (PSA) secretion. Furthermore, AR was silenced in the LNCaP and LNCaP-AI cells to detect the roles that AR plays in cell growth, apoptosis and PSA secretion. We found that prolonged androgen ablation increased the LNCaP-AI cell growth rate and cell invasiveness, and induced epithelial-mesenchymal transition in the LNCaP-AI cells. Moreover, despite the fact that the LNCaP and LNCaP-AI cells expressed equal amounts of AR protein, androgen induced a greater secretion of PSA in the LNCaP-AI cells than in the LNCaP cells. The proliferation of the LNCaP-AI cells was not dependent on, but was suppressed by androgen, which led to arrest at the G1 phase. Conversely, androgen significantly increased LNCaP cell proliferation by promoting the G1-S transition. Moreover, the silencing of AR suppressed LNCaP and LNCaP-AI cell growth by inducing cell cycle arrest at the G1 phase rather than promoting apoptosis, and reduced PSA secretion. On the whole, our data suggest that LNCaP-AI cells have a more more aggressive phenotype compared with the LNCaP cells; AR remains a critical factor in the LNCaP-AI cells, and androgen suppresses LNCaP-AI cell growth by blocking the cell cycle at the G1 phase.
doi:10.3892/ijmm.2017.3125
PMCID: PMC5627872  PMID: 28901378
androgen-independent LNCaP cells; growth suppression; cell cycle arrest; androgen; androgen receptor
5.  In-situ visualization of multiple filament competition dynamic during nonlinear propagation of femtosecond laser 
Scientific Reports  2017;7:10384.
In this work, multiple filamentation competition of femtosecond pulse in methanol is studied both experimentally and numerically. The visualization of multiple filamentation competition has been realized in the experiment performing the three-photon fluorescence of Coumarin 440. The random changes of multiple filamentation stemmed from the jitter of the peak laser intensity ratio of initial hot spots are first observed directly and visually, which can be well explained by a simplified (2D+1)-dimensional model.
doi:10.1038/s41598-017-10768-2
PMCID: PMC5583335  PMID: 28871115
6.  Gambling Disorder and Minority Populations: Prevalence and Risk Factors 
Current addiction reports  2016;3(3):280-292.
Purpose of review
Previous studies demonstrate disparities in health and health services including gambling disorders (GD) among ethnic and racial minority groups. In this review, we summarize studies examining the prevalence of GD across different ethnic and racial minorities.
Recent findings
We describe the sociodemographic subgroup variations at heightened risk for GD and factors associated with GD in racial and ethnic minority groups including gambling availability, comorbid substance use, psychiatric conditions, stress, acculturation, and differences in cultural values and cognitions. We found that research of GD among minority groups is scant, and the prevalence of GD among these groups is at a magnitude of concern.
Summary
Racial and ethnic minority status in it of itself is not a risk factor for GD but may be a proxy for underlying potential risk factors. The need for prevention and treatment programs for different cultural group remains unmet.
doi:10.1007/s40429-016-0108-9
PMCID: PMC5560497  PMID: 28824833
Gambling disorder; Racial minorities; Ethnic minorities; Risk factors
7.  Human influence on the temporal dynamics and spatial distribution of forest biomass carbon in China 
Ecology and Evolution  2017;7(16):6220-6230.
Abstract
Global carbon cycles are impacted by human activity primarily via fossil fuel combustion and forest carbon budget alterations. In this study, the temporal dynamics and spatial distribution of forest biomass carbon (FBC) stock and density in China were analyzed to assess the large‐scale effects of humans on FBC. The results indicated that from 1977 to 2013, the FBC stock increased by 62.9%, from 4,335 to 7,064 Tg C, owing to human‐driven forestation and ecological restoration programs. Because of intensive human impacts, 44.2%–54.6% of the FBC stock was concentrated in four provinces (Heilongjiang, Yunnan, Inner Mongolia, and Sichuan) and the FBC density increased from the densely populated southeastern provinces to the sparsely populated northeastern and western provinces. On a spatial scale, the FBC density was significantly negatively related to population density, and the degree of the dependence of the FBC density on population density has been declining since 1998. This improvement in human–forest relations is related to economic development and programs in China that have promoted forestation and reduced deforestation. These results suggest that human impacts, including forestation, deforestation, population density, and economic development, have played significant roles in determining the temporal and spatial variations of FBC in the anthropogenic era. Moreover, our findings have implications for forest management and improvement of the forest carbon sink in China.
doi:10.1002/ece3.3188
PMCID: PMC5574751  PMID: 28861227
carbon density; carbon stock; forestation; human activity; population density
8.  Association between human papillomavirus and prostate cancer: A meta-analysis 
Oncology Letters  2017;14(2):1855-1865.
Observational studies have suggested an association between human papillomavirus (HPV) infection and the risk of prostate cancer (PCa). However, the association between HPV infection and the risk of PCa remains unclear. The aim of the present meta-analysis study was to investigate whether HPV serves a role in increasing the risk of PCa. Relevant previous studies up to May 2015 were searched in PubMed, Web of Science, Cochrane library, Chinese National Knowledge Infrastructure, China Wan Fang database and China Biomedical Literature Database. A random-effects model or fixed-effects model was employed to determine odds ratios (ORs) with 95% confidence intervals (CIs), when appropriate. Heterogeneity was evaluated using Q and I2 statistical analysis. A total of 24 case-control studies involving 971 patients and 1,085 controls were investigated to estimate the association between HPV infection and PCa risk. The pooled estimate for OR was 2.27 (95% CI, 1.40–3.69). Stratified pooled analyses were subsequently performed according to the HPV detection methods, geographical regions, publication years and types of tissue. Sensitivity analysis based on various exclusion criteria maintained the significance with respect to PCa individually. Little evidence of publication bias was observed. The meta-analysis suggested that HPV infection is associated with increasing risk of PCa, which indicated a potential pathogenetic link between HPV and PCa.
doi:10.3892/ol.2017.6367
PMCID: PMC5529902
human papillomavirus; prostate cancer; meta-analysis
9.  Circulating tumor cells in prostate cancer: Precision diagnosis and therapy 
Oncology Letters  2017;14(2):1223-1232.
The primary cause of tumor-associated mortality in prostate cancer (PCa) remains distant metastasis. The dissemination of tumor cells from the primary tumor to distant sites through the bloodstream cannot be detected early by standard imaging methods. Circulating tumor cells (CTCs) represent an effective prognostic and predictive biomarker, which are able to monitor efficacy of adjuvant therapies, detect early development of metastases, and finally, assess therapeutic responses of advanced disease earlier than traditional diagnostic methods. In addition, since repeated tissue biopsies are invasive, costly and not always feasible, the assessment of tumor characteristics on CTCs, by a peripheral blood sample as a liquid biopsy, represents an attractive opportunity. The implementation of molecular and genomic characterization of CTCs may contribute to improve the treatment selection and thus, to move toward more precise diagnosis and therapy in PCa. The present study summarizes the current advances in CTC enrichment and detection strategies and reviews how CTCs may contribute to significant insights in the metastatic process, as well as how they may be utilized in clinical application in PCa. Although it is proposed that CTCs may offer insights into the prognosis and management of PCa, there are a number of challenges in the study of circulating tumor cells, and their clinical utility remains under investigation.
doi:10.3892/ol.2017.6332
PMCID: PMC5529747
prostate cancer; circulating tumor cell; liquid biopsy; epithelial-mesenchymal transition; metastasis; prognostic; predictive
10.  The inhibition of NOTCH2 reduces UVB-induced damage in retinal pigment epithelium cells 
Molecular Medicine Reports  2017;16(1):730-736.
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly. The pathogenesis of dry AMD remains indistinct and the mechanism of retinal pigment epithelium (RPE) cells death in dry AMD is controversial. The aim of the present study was to investigate the functions of Notch signaling in ultraviolet B (UVB)-induced damage of RPE cells. It was identified that, in RPE cells, UVB increased intracellular reactive oxygen species (ROS) and induced cell apoptosis. In addition, UVB activated Notch signaling in a dose dependent manner. Surprisingly, NOTCH2, but not NOTCH1, was demonstrated to be the major Notch receptor in RPE cells. Under normal conditions, the inhibition of NOTCH2 reduced cell growth and cell migration, but had no impact on intracellular ROS and cell apoptosis. However, in the presence of UVB, the inhibition of NOTCH2, but not NOTCH1, attenuated intracellular ROS and cell apoptosis. The function of Notch signaling involved in UVB damage of RPE cells may not only be significant to understanding the pathogenesis of AMD (especially dry AMD), but also useful for designing effective therapeutic agents for dry AMD.
doi:10.3892/mmr.2017.6625
PMCID: PMC5482198  PMID: 28560393
age-related macular degeneration; retinal pigment epithelium; ultraviolet B; Notch signaling
11.  Variations in Mental Health Diagnosis and Prescribing Across Pediatric Primary Care Practices 
Pediatrics  2016;137(5):e20152974.
BACKGROUND:
Primary care pediatricians increasingly care for children’s mental health problems, but little is known about practice-level variation in diagnosis and psychotropic medication prescribing practices.
METHODS:
This retrospective review of electronic heath records from 43 US primary care practices included children aged 4 to 18 years with ≥1 office visit from January 1, 2009, to June 30, 2014. We examined variability in diagnosis and psychotropic prescribing across practices using logistic regression with practice fixed effects and evaluated associations of the availability of colocated or community-based mental health providers or the proportion of children in foster care with diagnosis and prescribing using generalized linear mixed models.
RESULTS:
Among 294 748 children, 40 932 (15%) received a mental health diagnosis and 39 695 (14%) were prescribed psychotropic medication. Attention deficit/hyperactivity disorder was most commonly diagnosed (1%–16% per practice). The proportion of children receiving any psychotropic medication (4%-26%) and the proportion receiving ≥2 medication classes (1%-12%) varied across practices. Prescribing of specific medication classes also varied (stimulants, 3%–18%; antidepressants, 1%–12%; α-agonists, 0%–8%; second-generation antipsychotics, 0%–5%). Variability was partially explained by community availability of psychiatrists (significantly higher odds of a diagnosis or prescription when not available) but not by colocation of mental health professionals or percentage of children in foster care.
CONCLUSIONS:
The prevalence of mental health diagnosis and psychotropic medication prescribing varies substantially across practices and is only partially explained by psychiatrist availability. Research is needed to better define the causes of variable practice-level diagnosis and prescribing and implications for child mental health outcomes.
doi:10.1542/peds.2015-2974
PMCID: PMC4845867  PMID: 27244791
12.  RON and c-Met facilitate metastasis through the ERK signaling pathway in prostate cancer cells 
Oncology Reports  2017;37(6):3209-3218.
Prostate cancer (PCa) is a metastatic malignant cancer driven by complex pathological mechanisms and characterized by poor long-term prognosis. Metastasis is the main cause of death of PCa patients, yet the molecular mechanisms of this process are poorly understood. In the present study, positive co-expression of RON and c-Met was observed in human clinical PCa tissues (biopsy material), as detected by immunohistochemical staining and quantitative real-time PCR. We investigated this further in PCa cells, demonstrating that the inhibition of RON and c-Met with foretinib (GSK1363089) suppressed metastasis and promoted the reversal of the epithelial-to-mesenchymal transition (EMT) in PCa cells. Furthermore, the invasion and migration of PCa cells were enhanced by the exogenous activation of RON with MSP and c-Met with HGF, whereas silencing of RON and c-Met attenuated the invasion and metastasis of the PCa cells. Our data also demonstrated that HGF/c-Met, but not the MSP-RON signaling pathway may be the dominant mechanism for PCa EMT. We further revealed that RON and c-Met facilitate metastasis via ERK1/2 signaling. These findings indicate that RON and c-Met facilitate metastasis through ERK1/2 signaling and that targeting RON and c-Met with foretinib may be an attractive therapeutic option for suppressing PCa metastasis.
doi:10.3892/or.2017.5585
PMCID: PMC5442400  PMID: 28440432
RON; c-Met; metastasis; prostate cancer; ERK; foretinib
13.  Pectoralis Major Myocutaneous Flap for Head and Neck Defects in the Era of Free Flaps: Harvesting Technique and Indications 
Scientific Reports  2017;7:46256.
The role of the pectoralis major myocutaneous flap (PMMF) in head and neck reconstruction is challenged recently due to its natural drawbacks and the popularity of free flaps. This study was designed to evaluate the indications and reliability of using a PMMF in the current free flap era based on a single center experience. The PMMF was harvested as a pedicle-skeletonized flap, with its skin paddle caudally and medially to the areola, including the third intercostal perforator, preserving the upper one third of the pectoralis major muscle. The harvested flap was passed via a submuscular tunnel over the clavicle. One hundred eighteen PMMFs were used in 114 patients, of which 76 were high-risk candidates for a free flap; 8 patients underwent total glossectomy, and 30 underwent salvage or emergency reconstruction. Major complications occurred in 4 patients and minor complications developed in 10. Tracheal extubation was possible in all cases, while oral intake was possible in all but 1 case. These techniques used in harvesting a PMMF significantly overcome its natural pitfalls. PMMFs can safely be used in head and neck cancer patients who need salvage reconstruction, who are high risk for free flaps, and who need large volume soft-tissue flaps.
doi:10.1038/srep46256
PMCID: PMC5384233  PMID: 28387356
14.  Case management of patients with Type 2 diabetes mellitus: a cross-sectional survey in Chongqing, China 
Background
Type 2 diabetes mellitus has been identified as one of the priority diseases and included in the essential public health service package in China. This study investigated the frequency of follow-up visits and contents of care for case management of patients with Type 2 diabetes in Chongqing located in the western China, in terms of the regional practice guideline; and analyzed factors associated with the use of care.
Methods
A cross-sectional survey was conducted with patients diagnosed with Type 2 diabetes in two areas in Chongqing. Total 502 participants (out of 664 people eligible) completed the interview. The outcome measures included at least four follow-up visits in a year, annual HbA1c test, blood lipid test and diabetic screening for nephropathy and eyes. Logistic regression analysis was applied to examine the association between participants’ demographic and socio-economic characteristics and outcome measures.
Results
Over the one-year study period, 65% of participants had four or more follow-up visits. In light of the recommended tests, the proportions of having HbA1c test, blood lipid test and screening for nephropathy and eyes annually were 8, 54, 45 and 44%, respectively. After adjusting for study sites, age, sex, education, type of residence, level of income, the patients who were covered by Urban Employee Basic Medical Insurance, were enrolled in the targeted disease reimbursement program, and lived with diabetes more than five years were more likely to have regular follow-up visits and the recommended tests.
Conclusions
Case management for patients with Type 2 diabetes mellitus was not effectively implemented in terms of frequency of follow-up visits and recommended tests over one-year period, as indicated in the regional practice guideline.
doi:10.1186/s12913-017-2039-0
PMCID: PMC5303217  PMID: 28187724
Type 2 diabetes mellitus; Chronic disease case management; Compliance; China
15.  Distinct prognostic values of S100 mRNA expression in breast cancer 
Scientific Reports  2017;7:39786.
S100 family genes encode low molecular weight, acidic-Ca2+ binding proteins implicating in a wide spectrum of biological processes. S100 family contains at least 20 members, most of which are frequently dysregulated in human malignancies including breast cancer. However, the prognostic roles of each individual S100, especially the mRNA level, in breast cancer patients remain elusive. In the current study, we used “The Kaplan-Meier plotter” (KM plotter) database to investigate the prognostic values of S100 mRNA expression in breast cancer. Our results indicated that high mRNA expression of S100A8, S100A9, S100A11 and S100P were found to be significantly correlated to worse outcome, while S100A1 and S100A6 were associated with better prognosis in all breast cancer patients. We further assessed the prognostic value of S100 in different intrinsic subtypes and clinicopathological features of breast cancer. The associated results will elucidate the role of S100 in breast cancer and may further lead the research to explore the S100-targeting reagents for treating breast cancer patients.
doi:10.1038/srep39786
PMCID: PMC5209742  PMID: 28051137
16.  Roles of LncRNAs in Viral Infections 
Many proteins and signaling pathways participate in anti-viral host responses. Long non-coding RNAs (lncRNAs), a subset of non-coding RNAs greater than 200 nucleotides in length, have been recently described as critical regulators in viral infections. Accumulating research indicates that lncRNAs are important in the development and progression of infectious diseases. LncRNAs are not only involved in anti-viral responses, but in many different virus-host interactions, some of which may be beneficial to the virus. Here we review the current knowledge regarding host and viral lncRNAs and their roles in viral infections. In addition, the potential of using lncRNAs as diagnostic biomarkers is discussed.
doi:10.3389/fcimb.2017.00205
PMCID: PMC5445353
long non-coding RNAs; virus infection; cellular lncRNAs; virus-encoded lncRNAs; cell-virus interaction
17.  Tunable reflecting terahertz filter based on chirped metamaterial structure 
Scientific Reports  2016;6:38732.
Tunable reflecting terahertz bandstop filter based on chirped metamaterial structure is demonstrated by numerical simulation. In the metamaterial, the metal bars are concatenated to silicon bars with different lengths. By varying the conductivity of the silicon bars, the reflectivity, central frequency and bandwidth of the metamaterial could be tuned. Light illumination could be introduced to change the conductivity of the silicon bars. Numerical simulations also show that the chirped metamaterial structure is insensitive to the incident angle and polarization-dependent. The proposed chirped metamaterial structure can be operated as a tunable bandstop filter whose modulation depth, bandwidth, shape factor and center frequency can be controlled by light pumping.
doi:10.1038/srep38732
PMCID: PMC5150638  PMID: 27941833
18.  Anticancer activities of alkaloids extracted from the Ba lotus seed in human nasopharyngeal carcinoma CNE-1 cells 
To investigate the anticancer activities of alkaloids from the Ba lotus seed (BLSA) in human nasopharyngeal carcinoma (NPC) CNE-1 cells, an MTT assay, flow cytometry, reverse transcription-polymerase chain reaction and western blotting were performed. BLSA was found to significantly reduce CNE-1 cell proliferation in a dose-dependent manner at all concentrations compared with the control (P<0.05). In addition, flow cytometry analysis identified that BLSA treatment significantly increased the sub-G1 content in CNE-1 cells (P<0.05). Following BLSA treatment, the mRNA and protein levels of a number of apoptosis-related factors, such as caspase family members (caspase-3, −8 and −9), B-cell lymphoma (Bcl)-2-associated X protein, Fas and Fas ligand were significantly increased compared with the control (P<0.05). This was accompanied by a significant decrease in anti-apoptotic Bcl-2 and Bcl-extra large protein expression compared with the control (P<0.05). Furthermore, BLSA treatment was determined to modulate CNE-1 cell expression of nuclear factor (NF)-κB and NF-κB inhibitor α. The results of the present study indicate that BLSA has anticancer activity through inducing cellular apoptosis. In addition, these results suggest that BLSA can be used as a therapeutic agent in NPC.
doi:10.3892/etm.2016.3727
PMCID: PMC5103758  PMID: 27882126
alkaloids; Ba lotus seed; human nasopharyngeal carcinoma; CNE-1; apoptosis; caspase family
19.  Broadband terahertz metamaterial absorber based on sectional asymmetric structures 
Scientific Reports  2016;6:32466.
We suggest and demonstrate the concept and design of sectional asymmetric structures which can manipulate the metamaterial absorber’s working bandwidth with maintaining the other inherent advantages. As an example, a broadband terahertz perfect absorber is designed to confirm its effectiveness. The absorber’s each cell integrates four sectional asymmetric rings, and the entire structure composed of Au and Si3N4 is only 1.9 μm thick. The simulation results show the bandwidth with absorptivity being larger than 90% is extended by about 2.8 times comparing with the conventional square ring absorber. The composable small cell, ultra-thin, and broadband absorption with polarization and incident angle insensitivity will make the absorber suitable for the applications of focal plane array terahertz imaging.
doi:10.1038/srep32466
PMCID: PMC5004127  PMID: 27571941
20.  Social integration and maternal smoking: A longitudinal analysis of a national birth cohort 
Maternal and child health journal  2016;20(8):1586-1597.
Objectives
Social support and engagement are related to smoking behavior in general populations, but it is unknown whether these measures of social integration as experienced by recent mothers are related to longitudinal maternal smoking patterns. The purpose of this study is, first, to describe longitudinal patterns of maternal smoking before, during, and after pregnancy through the early childhood parenting years, as well as variation in these patterns; and second, to examine these patterns in relation to social integration, emotional, behavioral, and sociodemographic factors.
Methods
Among 9,050 mothers of the Early Childhood Longitudinal Study-Birth Cohort (a nationally representative probability sample of children born in 2001), we estimated trajectories of maternal smoking with general growth mixture model (GGMM), and examined how baseline predictors are associated with these patterns over a 5 to 6 year period beginning three months prior to pregnancy.
Results
A 5-class solution identified trajectories of nonsmokers (70.5%), temporary quitters (9.4%), pregnancy-inspired quitters (3.3%), delayed initiators (5.1%), and persistent smokers (11.7%). Modifiable risk factors included postpartum alcohol consumption and behavioral cues from co-resident smokers, while breastfeeding beyond six months and social engagement through religious service attendance were protective characteristics.
Conclusions
Prevention of and treatment for maternal perinatal and postpartum smoking is best informed by mothers’ emotional, behavioral and sociodemographic characteristics. Religious service attendance, but not measures of social support or social engagement, is a protective factor for maternal smoking trajectories.
doi:10.1007/s10995-016-1958-4
PMCID: PMC4958414  PMID: 26987858
maternal smoking patterns; social support; social engagement; community involvement; social connectedness; GGMM
21.  Controllable light capsules employing modified Bessel-Gauss beams 
Scientific Reports  2016;6:29001.
We report, in theory and experiment, on a novel class of controlled light capsules with nearly perfect darkness, directly employing intrinsic properties of modified Bessel-Gauss beams. These beams are able to naturally create three-dimensional bottle-shaped region during propagation as long as the parameters are properly chosen. Remarkably, the optical bottle can be controlled to demonstrate various geometries through tuning the beam parameters, thereby leading to an adjustable light capsule. We provide a detailed insight into the theoretical origin and characteristics of the light capsule derived from modified Bessel-Gauss beams. Moreover, a binary digital micromirror device (DMD) based scheme is first employed to shape the bottle beams by precise amplitude and phase manipulation. Further, we demonstrate their ability for optical trapping of core-shell magnetic microparticles, which play a particular role in biomedical research, with holographic optical tweezers. Therefore, our observations provide a new route for generating and controlling bottle beams and will widen the potentials for micromanipulation of absorbing particles, aerosols or even individual atoms.
doi:10.1038/srep29001
PMCID: PMC4937432  PMID: 27388558
22.  GPR30 decreases with vascular aging and promotes vascular smooth muscle cells maintaining differentiated phenotype and suppressing migration via activation of ERK1/2 
OncoTargets and therapy  2016;9:3415-3422.
Estrogen receptors, including classic nuclear receptors ERα, ERβ, and membrane receptor GPR30, are expressed in vascular tissues and exert protective actions in vascular diseases. But the expression pattern and functional roles of GPR30 in vascular smooth muscle cells (VSMCs) remain unclear. In this study, we found that ERα, ERβ, and GPR30 were decreased with VSMCs passaging in vitro or growing in vivo and activation of GPR30 promoted ERα expression. Then, we validated that activation of GPR30 significantly decreased migratory capability of VSMCs and suppressed ERα, whereas PDGF-BB (20 ng/mL) treatment caused increase of migration. And activation of GPR30 led to reduction of osteopontin and cellular retinol binding protein 1, enhancement of calponin and 3F8, and upregulation of total and phosphorylated ERK1/2 expression in VSMCs knocked down by GPR30, ERα, and ERβ or treated with PDGF-BB. These data suggest that GPR30 promotes VSMCs reducing migration and maintaining differentiated phenotype via activation of ERK1/2 pathway. Our findings provide novel mechanisms of GPR30 protection of VSMCs as well as a new target for prevention of vascular aging.
doi:10.2147/OTT.S104972
PMCID: PMC4907733  PMID: 27354813
vascular smooth muscle cell; estrogen receptor; G protein-coupled receptor 30; phenotype; migration
23.  Broadband diffuse terahertz wave scattering by flexible metasurface with randomized phase distribution 
Scientific Reports  2016;6:26875.
Suppressing specular electromagnetic wave reflection or backward radar cross section is important and of broad interests in practical electromagnetic engineering. Here, we present a scheme to achieve broadband backward scattering reduction through diffuse terahertz wave reflection by a flexible metasurface. The diffuse scattering of terahertz wave is caused by the randomized reflection phase distribution on the metasurface, which consists of meta-particles of differently sized metallic patches arranged on top of a grounded polyimide substrate simply through a certain computer generated pseudorandom sequence. Both numerical simulations and experimental results demonstrate the ultralow specular reflection over a broad frequency band and wide angle of incidence due to the re-distribution of the incident energy into various directions. The diffuse scattering property is also polarization insensitive and can be well preserved when the flexible metasurface is conformably wrapped on a curved reflective object. The proposed design opens up a new route for specular reflection suppression, and may be applicable in stealth and other technology in the terahertz spectrum.
doi:10.1038/srep26875
PMCID: PMC4881048  PMID: 27225031
24.  Interaction of Toll-Like Receptors with the Molecular Chaperone Gp96 Is Essential for Its Activation of Cytotoxic T Lymphocyte Response 
PLoS ONE  2016;11(5):e0155202.
The heat shock protein gp96 elicits specific T cell responses to its chaperoned peptides against cancer and infectious diseases in both rodent models and clinical trials. Although gp96-induced innate immunity, via a subset of Toll like receptors (TLRs), and adaptive immunity, through antigen presentation, are both believed to be important for priming potent T cell responses, direct evidence for the role of gp96-mediated TLR activation related to its functional T cell activation is lacking. Here, we report that gp96 containing mutations in its TLR-binding domain failed to activate macrophages, but peptide presentation was unaffected. Moreover, we found that peptide-specific T cell responses, as well as antitumor T cell immunity induced by gp96, are severely impaired when the TLR-binding domain is mutated. These data demonstrate the essential role of the gp96-TLR interaction in priming T cell immunity and provide further molecular basis for the coupling of gp96-mediated innate with adaptive immunity.
doi:10.1371/journal.pone.0155202
PMCID: PMC4868323  PMID: 27183126
25.  Changing Patterns of Alpha Agonist Medication Use in Children and Adolescents 2009–2011 
Abstract
Objectives: The purpose of this study was to describe rates and patterns of long- and short-acting alpha agonist use for behavioral problems in a primary care population following Food and Drug Administration (FDA) approval of the long-acting alpha agonists guanfacine and clonidine.
Methods: Children and adolescents 4–18 years of age, who received an alpha agonist prescription between 2009 and 2011, were identified from a sample of 45 United States primary care practices in two electronic health record-based research networks. Alpha agonist receipt was identified using National Drug Codes and medication names. The proportion of subjects receiving long- and short-acting prescriptions in each year was calculated and examined with respect to reported mental health diagnoses, and whether indications for use were on-label, had evidence from clinical trials, or had no trial evidence.
Results: In a cohort of 282,875 subjects, 27,671 (10%) received any psychotropic medication and only 4,227 subjects (1.5%) received at least one prescription for an alpha agonist, most commonly a short-acting formulation (83%). Only 20% of alpha agonist use was on-label (use of long-acting formulations for attention-deficit/hyperactivity disorder [ADHD]). Most subjects (68%) received alpha agonists for indications with evidence of efficacy from clinical trials but no FDA approval, primarily short-acting formulations for ADHD and autism; 12% received alpha agonists for diagnoses lacking randomized clinical trial evidence in children, including sleep disorders and anxiety, or for which there was no documented mental health diagnosis. Rates of long-acting alpha agonist use increased more than 20-fold from 0.2% to 4%, whereas rates of short-acting alpha agonist use grew only slightly between 2009 and 2011 from 10.6% to 11.3%.
Conclusions: Alpha agonist use was uncommon in this population, and most subjects received short-acting forms for conditions that were off-label, but with clinical trial evidence. The safety and efficacy of use for conditions, including sleep disorders and anxiety, lacking evidence from randomized trials, warrant further investigation.
doi:10.1089/cap.2014.0122
PMCID: PMC4442562  PMID: 25919708

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