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The purpose of this study was to evaluate the potential predictor of tumor size on rates of overall and disease-free survival (OS and DFS) as determined by postoperative pathologic examination in patients with glottic carcinoma.Retrospective cohort study.Tertiary care university hospital.In this study, 1337 consecutive patients with glottic carcinoma who underwent surgical treatment from 2005 to 2010 were retrospectively reviewed. The influence of tumor size that was evaluated by tumor area (tumor length × tumor width) on OS and DFS outcomes was assessed by Cox regression analyses.In all, 1303 (97.5%) patients were male, and 34 (2.5%) were female, with a mean ± SD age of 60.4 ± 10 years. The 10-year OS and DFS rates were 72.9% and 69.9%, respectively. The tumor area cutoff values that best discriminated OS and DFS rates were both 1.80 cmThe results of this study indicate that patients with glottic carcinoma with a tumor area1.8 cm

Wetland restoration has been implemented widely but evaluation of the effectiveness of wetland restoration has been limited. In this study, we aimed to investigate the utility of aquatic invertebrate assemblages as potential indicators of restoration condition in wetlands of the Sanjiang Plain, Northeastern China. Results from non‐metric multidimensional scaling analysis of invertebrate assemblages showed that study wetlands (n = 16) divided into two groups: natural wetlands and wetlands that have been restored for 4 years were classified as a group, and impaired wetlands and wetlands restored for only 1 year were classified into another group. After 4 years of recovery, 47.9% of invertebrate taxa found at the natural wetlands could also be found at the restored wetlands, primarily insects with aerial dispersal capabilities for rapid colonization. Indicator species analysis identified differences in community composition among wetland types, and Amphiagrion sp. and Bezzia sp. were indicators of the restored wetlands. In Northeastern China, aquatic invertebrate assemblages and certain indicator species may provide robust measures of wetland restoration. It is urgent for further exploration to monitor restored wetlands in the long‐time series and fully assess the efficiency of the restoration.

Background To investigate the therapeutic mechanism of the BRD4 inhibitor JQ1 in SACC-83 cells and explore strategies to enhance its therapeutic potential. Material and methods SACC-83 cells were used in the experiment. Immunohistochemistry was used to assess BRD4 expression in SACC tissues and corresponding adjacent non-tumor tissues. Cell viability and proliferation were evaluated using the Cell Counting Kit-8 assay. Flow cytometry was used to quantitate apoptosis. Levels of cleaved caspase-3, BRD4, c-Myc, pEGFR (γ-1173), and EGFR were determined by quantitative real-time PCR and Western blot. To study the role of EGFR in JQ1 resistance, we generated EGFR knockdown SACC-83 cells by siRNA transfection. Results Our study revealed that BRD4 was overexpressed and could be a treatment target in SACC. The BRD4 inhibitor JQ1 markedly inhibited c-Myc expression in SACC-83 cells, which produced modest therapeutic effects. Nevertheless, the EGFR pathway was strongly activated following JQ1 treatment, which led to JQ1 resistance. Combined JQ1 and PI3K inhibitor treatment effectively increased the therapeutic potential by inhibiting the EGFR and c-Myc signaling pathways in SACC-83 cells. Moreover, EGFR knockdown sensitized SACC-83 cells to JQ1. Conclusion These data demonstrate that EGFR and c-Myc signaling synergistically drive SACC progression. The JQ1 and PI3K inhibitor combination exhibited a strong synergistic effect by suppressing c-Myc and EGFR in SACC-83 cells, identifying a novel rational combinatorial treatment. Moreover, EGFR expression influences the sensitivity of SACC-83 cells to JQ1, which is useful for planning treatment.

Inhibiting BRD4 has emerged as a promising anticancer strategy, and inhibitors such as JQ1 can suppress cell growth in oral squamous cell carcinoma (OSCC). However, the mechanism through which JQ1 exerts its anticancer activity has not been reported. Moreover, JQ1 does not markedly inhibit proliferation and increase apoptosis in OSCC when used as a monotherapy. Herein, we explore the mechanism of JQ1 in OSCC and probe ways to increase its therapeutic potential. In this study, we used two cell lines, Cal27, and Scc25. We found that BRD4 was highly expressed in OSCC tissues when compared with adjacent non-tumor tissues, and JQ1 worked through the EGFR-mediated signaling pathway in tumor cells. Furthermore, we demonstrated that JQ1 induced an increased treatment effect in vitro and in vivo when combined with a PI3K inhibitor. Interestingly, subsequent mechanistic analyses indicated that further suppressing EGFR and BRD4 expression was instrumental to this functional synergism. Moreover, we found that upregulating EGFR expression by EGF stimulation protected cells treated with JQ1 from apoptosis, while knockdown of EGFR before addition of JQ1 successfully mimicked the combination treatment results. In summary, our findings revealed that JQ1 can act by inhibiting the EGFR-mediated signaling pathway, and EGFR expression influences the sensitivity of OSCC to JQ1. Regarding clinical use, this study demonstrates that BRD4 is a novel therapeutic target and EGFR can be used as a biomarker to identify the most appropriate anti-BRD4 treatment strategy in OSCC.

Anthropogenic activities and natural causes contribute to the increase of the area and degree of degraded saline wetlands in arid/semi‐arid and coastal regions. The objective of this study was to determine the salt tolerance of seven aquatic plant species during asexual reproduction and at continued growth stage. The species were exposed to five salinity treatments from 0.3 (control) to 20 dS/m during the 30 day experiment. Data were collected on asexual reproduction and growth, chlorophyll content index in leaves, Na+ and K+ concentrations and total nitrogen (TN) and total phosphorus (TP) concentrations in above‐ground biomass (AGB) and below‐ground biomass (BGB). The results of this study showed that: 1) the increase of salinity (especially at a salinity level of EC≥15 dS/m) generally inhibited the capacity for asexual reproduction and reduced the chlorophyll content index in leaves; 2) total dry biomass of plants was significantly and negatively related to asexual reproduction of plants; 3) species‐specific salt tolerance mechanisms were shown as indicated by the Na+ and K+ concentrations and Na+/K+ ratios in different parts of plants; and 4) the absorption of TN and TP were inhibited at high salinity level (i.e., EC=20 dS/m) in AGB and BGB of most tested plant species. Salinity may enhance plant uptake of TN and TP under certain condition (e.g., EC at 5, 10 and 15 dS/m). In general, giant reed (Arundo donax) and alligator weed (Alternanthera philoxeroides) showed better asexual reproduction and growth capacity under high salt stress, and they should be considered as potential plant species to be used in the restoration of degraded saline wetlands and/or in treatment wetlands for decontaminating saline wastewater.

Background The purpose of this study was to assess the clinical results of patients with T3 glottic laryngeal carcinoma treated with total laryngectomy or partial laryngectomy. Methods We conducted a retrospectively review of 307 patients with T3 glottic laryngeal squamous cell carcinoma (SCC). Results The 5-year cancer-specific survival (CSS) rate was 71.5% and the overall survival (OS) rate was 70.6%. For patients who underwent total laryngectomy, the 5-year disease-free survival (DFS) rate was 59.8%, and the CSS rate was 67.9%. For partial laryngectomy, the 5-year DFS rate was 64.8%, and the CSS rate was 78.0%. High lymph node and stage status are predictors of mortality for these patients. No difference was found in DFS and CSS rates between patients with negative margins and those with positive margins after postoperative radiotherapy and chemotherapy. Conclusion Postoperative radiotherapy and chemotherapy are effective treatments for patients with T3 glottic laryngeal carcinoma, especially with a positive margin. For selected patients with T3 glottic laryngeal carcinoma, partial laryngectomy is a good choice because it can achieve satisfactory oncologic results while preserving laryngeal function.

Many publications have reported the growing application of complementary and alternative medicine, particularly the use of Chinese herbal medicine (CHM) in combination with routine pharmacotherapy (RP) for senile vascular dementia (SVD), but its efficacy remains largely unexplored. The purpose of this study is to evaluate the efficacy of CHM adjunctive therapy (CHMAT), which is CHM combined with RP, in the treatment of SVD. Publications in seven electronic databases were searched extensively, and 27 trials with a total of 1961 patients were included for analysis. Compared with RP alone, CHMAT significantly increased the effective rate [odds ratio (OR) 2.98, 95% confidence interval (CI) 2.30, 3.86]. In addition, CHMAT showed benefits in detailed subgroups of the Mini-Mental State Exam (MMSE) score from time of onset to 4 weeks (WMD 3.01, 95% CI 2.15, 3.87), 8 weeks (weighted mean difference (WMD) 2.30, 95% CI 1.28, 3.32), 12 weeks (WMD 2.93, 95% CI 2.17, 3.69), and 24 weeks (WMD 3.25, 95% CI 2.61, 3.88), and in the activity of daily living scale score from time of onset to 4 weeks (WMD -4.64, 95% CI -6.12, -3.17), 8 weeks (WMD -4.30, 95% CI -6.04, -2.56), 12 weeks (WMD -3.89, 95% CI -4.68, -3.09), and 24 weeks (WMD -4.04, 95% CI -6.51, -1.57). Moreover, CHMAT had positive effects on changes in the Hasegawa dementia scale, National Institutes of Health Stroke Scale, Clinical Dementia Rating, and Montreal Cognitive Assessment scores, as well as blood fat levels (total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and apolipoprotein E), platelet aggregation rate (1-min platelet aggregation rate, 5-min platelet aggregation rate, and maximal platelet aggregation rate), and blood rheology (whole-blood viscosity and hematocrit). No serious or frequently occurring adverse effects were reported. Weaknesses of methodological quality in most trials were assessed using the Cochrane risk of bias tool, while the quality level of Grades of Recommendations Assessment Development and Evaluation (GRADE) evidence classification indicated 'very low'. This systematic review suggests that CHM as an adjunctive therapy can improve cognitive impairment and enhance immediate response and quality of life in SVD patients. However, because of limitations of methodological quality in the included studies, further research of rigorous design is needed.

Nanoscopy has now become a real procedure in fluorescence microscopy of living cells. The STED/RESOLFT family of nanoscopy approaches has the best prospects for delivering high speed imaging, but the history of STED includes a continuing struggle to reduce the deactivation power applied, along with difficulties in achieving simultaneous multicolor images. In this manuscript, we present a concept for a similar real-time nanoscopy, using a new class of bipartite probes that separate the luminescent and quenching functions into two coupled molecules. In particular, the STAQ (Superresolution via Transiently Activated Quencher) example we show herein employs the excited state absorbance (not ground state) of the partner to accept energy from and quench the luminescent dye. The result is that much less deactivation power is needed for superresolved (∼50 nm) imaging. Moreover, the TAQ partner excited by the “donut” beam is shown to quench several different visible dyes via the same mechanism, opening the door to easier multicolor imaging. We demonstrate three dyes sharing the same deactivation and show examples of superresolved multicolor images. We suggest STAQ will facilitate the growth of real-time nanoscopy by reducing confounding photodamage within living cells while expanding the nanoscopist's palette. Microsc. Res. Tech. 78:343–355, 2015. Published 2015. This article is a U.S. Government work and is in the public domain in the USA

Apolipoprotein E (apoE) is predominantly synthesized by astrocytes in the brain. In this study, we investigated the role of apoE in astrocyte apoptosis. We demonstrated that apoE protects astrocytes from hypoxia-induced apoptosis in a dose-dependent manner. Glutamate release from astrocytic cultures is significantly lower from WT mice than from apoE knockout mice. Furthermore, the protective effect of apoE is mimicked by an NMDA receptor antagonist, MK-801. Finally, the apoE activator T0901317 significantly reduced the effect of glutamate-induced apoptosis of astrocytes. These results suggest that apoE protects astrocytes from hypoxia-induced apoptosis associated to NMDA receptor activation. Approaches that elevate apoE secretion in astrocytes might provide a novel strategy in the protection of neuronal ischemic injury.

The use of small interfering RNAs (siRNAs) to down-regulate the expression of disease-associated proteins carries significant promise for the treatment of a variety of clinical disorders. One of the main barriers to the widespread clinical use of siRNAs, however, is their entrapment and degradation within the endolysosomal pathway of target cells. Here we report the trafficking and function of PP75, a non-toxic, biodegradable, lipid membrane disruptive anionic polymer composed of phenylalanine derivatized poly(L-lysine iso-phthalamide). PP75 is readily endocytosed by cells, safely permeabilizes endolysosomes in a pH dependent manner and facilitates the transfer of co-endocytosed materials directly into the cytoplasm. The covalent attachment of siRNAs to PP75 using disulfide linkages generates conjugates that effectively traffic siRNAs to the cytoplasm of target cells both in vitro and in vivo. In a subcutaneous malignant glioma tumor model, a locally delivered PP75-stathmin siRNA conjugate decreases stathmin expression in tumor cells and, in combination with the nitrosourea chemotherapy carmustine, is highly effective at inhibiting tumor growth. PP75 may be clinically useful for the local delivery of siRNAs, in particular for the treatment of solid tumors.

Citation Zhong Y-P, Ying Y, Wu H-T, Zhou C-Q, Xu Y-W, Wang Q, Li J, Sheng X-T, Li J. Impact of anticardiolipin antibody on the outcome of in vitro fertilization and embryo transfer. Am J Reprod Immunol 2011; 66: 504–509 Problem To investigate the impact of anticardiolipin antibody (ACA) on the outcome of in vitro fertilization and embryo transfer (IVF-ET). Methods A total of 76 infertile women positive for anticardiolipin antibody (ACA+ group) and 819 controls negative for anticardiolipin antibody (ACA− group) undergoing IVF-ET in the First Affiliated Hospital, to Sun Yat-Sen University, were retrospectively analyzed. Women were diagnosed as having pure tubal factor infertility. Results The proportion of patients with a history of spontaneous abortion in the ACA+ group was significantly higher than that in ACA− group (19.7% versus 8.9%). The IVF rate, pregnancy rate and implantation rate in the ACA+ group were markedly lower than those in the ACA− group (75.5% versus 78.9%, 31.3% versus 48.6% and 16.1% versus 28.1%, respectively). Furthermore, the incidence of pregnancy loss in the ACA+ group was higher than that in the ACA− group (32.0% versus 15.1%). Conclusion ACA-positive patients had significantly decreased IVF rate, pregnancy rate and implantation rate and high risk of abortion. Therefore, ACA positivity predicts poor outcome of IVF-ET, and pre-treatment to lower ACA level may be clinically beneficial for patients receiving IVF-ET.

Fluorine-18-labeled lapatinib has been successfully synthesized for the first time by the reaction of a dimethylformamide solution of meta-[18F]fluorobenzylbromide with a Boc-protected lapatinib precursor fragment. The reaction proceeded in the presence of K2CO3 at 110 °C for 10 min in a microwave and was followed by Boc-group deprotection with trifluoroacetic acid. The overall radiochemical yield of the reaction starting from the radiofluorination of the iodonium salt was 8–12% (uncorrected, n = 6) in a 140-min synthesis time.

18F-labeled fluorobenzaldehydes and fluorobenzylbromides are useful synthons for the preparation of positron emission tomography radiopharmaceuticals. Although ortho- and para-[18F]fluorobenzaldehydes can easily be prepared with high yields, the corresponding meta-derivatives are more problematic. In order to improve the yield of meta-[18F]fluorobenzaldehyde, we used the corresponding diaryliodonium salt precursors, since diaryliodonium salts had already been used as precursors in the preparations of 18F-labeled electron-rich, as well as electron-deficient, aromatic rings. Diaryliodonium salts with different counter ions [PhIPhCHO]X (X = Cl, Br, OTs, OTf) were synthesized. 18F radiolabeling was performed using different bases at different temperatures in the presence of a radical scavenger, 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO). The best conversion (∼80%) to meta-[18F]fluorobenzaldehyde was obtained using CsHCO3 base at a reaction temperature of 110°C. To study iodonium salt counter ion effects on radiofluorination, each precursor was separately treated with Cs[18F]F/CsHCO3 in DMF at 110°C for 5 min in the presence of TEMPO. Our observed reactivity order was OTs

Objectives/Hypothesis: To investigate the potential usefulness of indirect computed tomography lymphography (CT-LG) with iopamidol in the detection of cervical lymph node metastases in a VX2 rabbit tongue cancer model. Study Design: Randomized controlled trial. Methods: Thirty-seven rabbits were randomly divided into control (n = 7) and tongue tumor-bearing (n = 30) groups. In the control group, indirect CT-LG was performed with 0.5- and 0.25-mL injections of iopamidol in the right and left tongue submucosa, respectively. In the tumor-bearing group, indirect CT-LG with 0.5 mL of iopamidol was performed on day 11 (n = 8), 14 (n = 8), 21 (n = 8), or 28 (n = 6) after carcinoma transplant. The correlation between indirect CT-LG and histopathology was investigated. Results: In normal rabbits, oval or round enhanced cervical lymph nodes in each side of the neck were visualized by indirect CT-LG. In tumor-bearing rabbits, one enhanced lymph node on each side of the neck was visualized with or without filling defects in all rabbits except two on day 28 in which lymph nodes were not enhanced. The sensitivity, specificity, accuracy, and positive and negative predictive values for using filling defects on CT-LG as a diagnostic criterion were 77.4%, 77.8%, 77.6%, 80%, and 75%, respectively. Indirect CT-LG detected 84.6% of 2- to 6-mm intranodal tumor deposits. Conclusions: Indirect CT-LG may be useful for differentiating metastatic from nonmetastatic lymph nodes. Laryngoscope, 2011

The present paper assesses the impact of improved upland rice technology on farmers’ well-being. The study uses propensity-score matching to address the problem of ‘self-selection,’ because technology adoption is not randomly assigned. It applies this procedure to household survey data collected in Yunnan, China in 2000, 2002 and 2004. The findings indicate that improved upland rice technology has a robust and positive effect on farmers’ well-being, as measured by income levels and the incidence of poverty. The effect of technology on well-being shows a diminishing impact on producers’ incomes. This implies that newer innovations are continuously needed to replace older technologies that have reached their saturation points. asej_2033 141..159

9-Carboranylcarbene is formed by reaction of carbon atoms with o-carborane. The triplet state reacts with alkenes by hydrogen abstraction, not the more usual addition reaction.