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Radiofrequency ablation and cryoballoon ablation are the main methods of catheter ablation for patients with atrial fibrillation (AF). However, different ablation catheters have different efficacy and complication rates. This study aimed to compare the efficacy and complication rates of quantitative radiofrequency ablation guided by ablation index (RFCA-AI) with those of second-generation cryoballoon ablation (CBA-2).A total of 230 consecutive patients with symptomatic AF undergoing a first ablation procedure of CBA-2 (92 patients) or RFCA-AI (138 patients) were enrolled in this study.The late recurrence rate in the CBA-2 group was higher than that in the RFCA-AI group (p = 0.012). Subgroup analysis showed the same result in patients with paroxysmal AF (PAF) (p = 0.039), but no difference was found in patients with persistent AF (p = 0.21). The average operation duration in the CBA-2 group (85 (75-99.5) min) was shorter than that in the RFCA-AI group (100 (84.5-120) min), but the average exposure time in the CBA-2 group (17.36 (13.87-22.49) min vs 5.49 (4.00-8.24) min; p0.0001) and X-ray dose (223.25 (149.15-336.95) min vs 109.15 (80.75-168.7) min; p0.0001) were significantly longer than those in RFCA-AI group. The patients were then divided into a late recurrent group and a late recurrence-free group. Multivariate logistic regression analysis showed that left atrial diameter (LAD), early recurrence, and methods of ablation (cryoballoon ablation) were independent risk factors for late recurrence after AF ablation.For patients with PAF, CBA-2 was inferior to RFCA-AI. Furthermore, although RFCA-AI had an equivalent complication rate and longer operation time than CBA-2, it also had a shorter exposure time and required a lower radiation dose. The early recurrence of AF and LAD were independent risk factors for predicting late recurrence after AF ablation (Tab. 5, Fig. 3, Ref. 29).

Background Renal cell carcinoma (RCC) is a common tumor of the urinary system. Nowadays, immunotherapy is a hot topic in treatment of solid tumors, especially those with pre-activated immune state. Methods In this study, we have downloaded genomic and clinical data of RCC samples from TCGA database. Four immune-related genetic signatures were used to predict the prognosis of RCC by Cox regression analysis. We have established a prognostic risk model. The model consists of the genes most related to prognosis from the four genes signatures and aims at prognosis of the RCC samples via Kaplan-Meier survival analysis. Independent data from the ICGC database were used to test the predictive stability of the model. Furthermore, we have performed landscape analysis to assess the presence of mutations in the genes of interest in the RCC samples from the TCGA. Finally, we have explored the correlation between the selected genes and the level of tumor immune infiltration via TIMER platform. Results We have used four genetic signatures to construct prognostic risk models and found that each of the models divide the RCC samples into high- and low-risk groups, each of the groups correlating with significantly different prognosis, especially in the advanced RCC cases. A comprehensive prognostic risk model was constructed with eight candidate genes from four signatures (HLA-B, HLA-A, HLA-DRA, IDO1, TAGAP, CIITA, PRF1 and CD8B) dividing the advanced RCC samples from the TCGA database into high-risk and low-risk groups with a significant difference in the overall survival. The stability of the model was verified by independent data from the ICGC database. The samples from different subgroups. Landscape analysis showed that the mutation ratios in some genes were different between two risk groups. Besides, the expression levels of the selected genes were interrelated with the infiltration degree of the immune cells in the advanced RCC. ConclusionsEight immune-related genes were screened in our study to construct a promising prognostic risk model with a great predictive value for the prognosis of advanced RCC. The selected genes were associated with infiltrating immune cells in tumors which presents a chance for personalized treatment for advanced RCC.

Fullerene (C60) L-phenylalanine derivative attached with poly (lactic acid) (C60-phe-PLA) was developed to prepare injectable Mitoxantrone (MTX) multifunctional implants. C60-phe-PLA was self-assembled to form microspheres consisting of a hydrophilic antitumor drug (MTX) and a hydrophobic block (C60) by dispersion-solvent diffusion method. The self-assembled microspheres showed sustained release pattern almost 15days in vitro release experiments. According to the tissue distribution of C57BL mice after intratumoral administration of the microspheres, the MTX mainly distributed in tumors, and rarely in heart, liver, spleen, lung, and kidney. Photodynamic antitumor efficacy of blank microsphere was realized. Microspheres afforded high antitumor efficacy without obvious toxic effects to normal organs, owing to its significantly increased MTX tumor retention time, low MTX levels in normal organs and strong photodynamic activity of PLA-phe-C60. These C60-phe-PLA microspheres may be promising for the efficacy with minimal side effects in future treatment of solid tumors.

Early-life stress in adolescence has a long-lasting influence on brain function in adulthood, and it is mostly recognized as a predisposing factor for mental illnesses, such as anxiety and posttraumatic stress disorder. Previous studies also indicated that adolescent predictable chronic mild stress (PCMS) in early life promotes resilience to depression- and anxiety-like behaviors in adulthood. However, the role of PCMS in associated memory process is still unclear. In the present study, we found that adolescent PCMS facilitated extinction and inhibited fear response in reinstatement and spontaneous recovery tests in adult rats, and this effect was still present 1 week later. PCMS in adolescence increased the activity of brain-derived neurotrophic factor (BDNF)-extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in infralimbic cortex (IL) but not prelimbic cortex in adulthood. Intra-IL infusion of BDNF antibody and the ERK1/2 inhibitor U0126 reversed PCMS-induced enhancement of fear extinction. Moreover, we found that PCMS decreased DNA methylation of the Bdnf gene at exons IV and VI and elevated the mRNA levels of Bdnf in the IL. Our findings indicate that adolescent PCMS exposure promotes fear memory extinction in adulthood, which reevaluates the traditional notion of adolescent stress.

A new type lacquer coating was developed by adding certain molecular weight of chitosan to the Rhus vernicifera lacquer sap. The optimum range of chitosan molecular weight and adding quantity were investigated, and the blended lacquer coating was prepared based on these results. The properties, such as molecular weight distribution, particle size distribution, drying times, and gel fraction were examined. In addition, the reaction between urushiol and chitosan is discussed based on the results of nuclear magnetic resonance (NMR) and infrared (IR) measurements. A blended lacquer coating with 3% chitosan dissolve in 5% of citric acid showed almost the same drying time and film hardness as 100% R. vernicifera lacquer sap as examined in an automatic drying time recorder, but had lighter surface color. Furthermore, the UV resistance and viscoelastic property also were investigated in detail.

Cognition is impacted by aging. However, the mechanisms that underlie aging-associated cognitive impairment are unclear. Here we showed that cognitive decline in aged rats was associated with changes in DNA methylation of protein kinase Mζ (PKMζ) in the prelimbic cortex (PrL). PKMζ is a crucial molecule involved in the maintenance of long-term memory. Using different behavioral models, we confirmed that aged rats exhibited cognitive impairment in memory retention test 24 h after training and overexpression of PKMζ in the PrL rescued cognitive impairment in aged rats. After fear conditioning, the protein levels of PKMζ and the membrane expression of GluR2 increased in the PrL in young and adult rats but not in aged rats and the levels of methylated PKMζ DNA in the PrL decreased in all age groups, whereas the levels of unmethylated PKMζ DNA increased only in young and adult rats. We also found that environmentally enriched housing reversed the hypermethylation of PKMζ and restored cognitive performance in aged rats. Inactivation of PKMζ prevented the potentiating effects of environmental enrichment on memory retention in aged rats. These results indicated that PKMζ might be a potential target for the treatment of aging-related cognitive impairment, suggesting a potential therapeutic avenue.

Wind turbine system with Permanent Magnet Synchronous Generator (PMSG) is a complex nonlinear system of multi-interference and strong coupling, so its accurate mathematical model is difficult to be built. Due to the randomness of the wind, traditional PID control is often hard to get satisfactory results in the Maximum Power Point Tracking (MPPT) control of the wind turbine. A new adaptive optimization control based on action dependent heuristic dynamic programming (ADHDP) is presented to control the stator current of PMSG. The stator current of the generator can adapt the change of the wind speed, so the MPPT of PMSG can be achieved. Simulation results in Matlab/Simulink show that the ADHDP controller can get better performances than PID controller.

a new method of locating the pinch is presented for the design of heat exchanger networks. The method is based on the pinch design method for heat exchanger networks which was first introduced by Linnhoff. The method first consider both the heat loss of a hot stream and the heat capacity flowrate of a stream with variation in temperature in the design of heat exchanger networks. Which affect not only minimum utility requirement for heat exchanger network but also the pinch location, choice ofΔTmin

a novel method of locating the pinch is presented for the design of heat exchanger networks. The method is based on the pinch design method for heat exchanger networks which was first introduced by Linnhoff. The method first consider the heat capacity flowrate of a stream with variation in temperature. This is because heat capacity flowrate of a stream with variation in temperature not only affect minimum utility requirement for heat exchanger network but also affect the pinch location, choice ofΔTmin.

The technology for bleaching of the starch glycoside surfactant was studied by using hydrogen peroxide as the major decoloring agent, coupled with magnesium sulfate, sodium silicate and EDTA as additive agents. The technic of decoloration was optimized through the orthogonal experimentation. Under the optimal experimental conditions, the resulting products exhibit good stability. After 72h stability test, only a little change of 1.01% by U-2001 spectrophotometer at absorbance 470 nm. The absorbance was observed by compared with the products before decoloration and after. The main composition and structure of the starch glycoside surfactant were analyzed by infrared spectrum (IR) and gas chromatography (GC). The experimental results show that the technics of decoloration for the starch glycoside surfactant are feasible and simple which may be useful for practical applications.

This report explores some properties of 80-200 nm nanoparticles containing 5-aminolevulinic acid (ALA) and fullerene (C60) for photodynamic therapy (PDT). Compared with ALA, the nanoparticles yielded more protoporphyrin IX (PpIX) formation in cells and tissues and to a significant improvement in antitumor efficacy in tumor-bearing mice. Maximum levels of PpIX were obtained 4 h after administration and selective PpIX formation in tumor was observed. These nanoparticles appear to be a useful vehicle for drug delivery purposes. In this study, a procedure for preparing fullerene nanoparticles containing ALA was developed. The product alone exhibited no detectable toxicity in the dark and was superior to ALA alone in promoting PpIX biosynthesis and PDT efficacy both in culture and in a murine tumor model. These results suggest that this procedure could be the basis for an improved PDT protocol for cancer control.

The properties of an ideal photosensitizer are water solubility, low cytotoxicity in the dark, high ability to produce reactive oxygen species (ROS). The characteristics of water-soluble fullerene (C60) amino acid nanoparticles as a photosensitizer were evaluated. C60 modified with l-phenylalanine (C60-phe) or glycine (C60-gly) was very efficient to carry out photodynamic activity leading to cleavage of plasmid DNA in vitro. These C60 amino acid nanoparticles were the most active photosensitizer against human Liver cancer cells and induced cancer cells apoptosis after illumination. However, these derivatives exhibited no significant cytotoxicity in dark. It produced diffuse intracellular fluorescence when 2',7'-dichlorfluorescein-diacetate (DCFH-DA) was added as an ROS probe, suggesting phototoxicity of these derivatives related with the generation of intracellular ROS. These findings indicate that these fullerene derivatives may be excellent candidate PDT enhancing agents.

The photocytotoxicity of water-dispersed 100–300 nm fullerene amino acid derivatives nanoparticles was studied. The nanoparticle solution of fullerene derivatives, l-phenylalanine (C60-phe) and glycine (C60-gly), suppressed the in vitro growth of MCF-7 cells lines, induced cancer cells apoptosis, and caused a perturbation of the cell cycle. These nanoparticle solutions increased intracellular reactive oxygen species after irradiation. C60-phe or C60-gly upregulated the expression of phosphorylated (p)p38 mitogen-activated protein kinase (MAPK). N-Acetyl-l-cysteine significantly depressed the composite-induced activation of p38MAPK, and the kinase inhibitor SB203580 significantly prevented C60 derivative-induced cell apoptosis. This study revealed that p38MAPK is activated by C60 nanoparticles through triggering reactive oxygen species generation, leading to cancer cell injuries.

To investigate the time course of myocardial NF-kappaB activation and association with cardiac function and other pro-inflammation cytokines following coronary microembolization (CME).CME was induced by homologous microthrombotic particle suspension injection into left ventricle with simultaneous short-term ascending aorta clamping. The CME rats were randomized to untreated group and pyrrolidine dithiocarbamate (PDTC, a specific NF-kappaB inhibitor) treated group (n = 32 respectively). The rats were sacrificed on day 1, 3, 7 and 14 post-operationally (n = 8 each). Twenty-four rats were sham-operated and served as controls. NF-kappaB DNA-binding activity was evaluated by electrophoretic mobility shift assay (EMSA), protein expressions of TNFalpha, IL-6 and ICAM-1 were analyzed by Western blotting, the dynamic alterations of TNFalpha, IL-6 and ICAM-1 mRNA were quantitatively assessed by Real-time PCR post hemodynamic measurements.NF-kappaB DNA-binding activity in CME group was significantly increased than that of sham group on day 1, peaked at day 3 and was similar as that in sham rats on day 14. The protein and mRNA expressions of TNFalpha, IL-6 and ICAM-1 were significantly increased in CME group at various time points compared those in sham rats. NF-kappaB DNA-binding activity positively correlated with mRNA expressions of TNFalpha, IL-6, ICAM-1, respectively (r = 0.72, P0.05; r = 0.94, P0.01; r = 0.62, P0.05). PDTC significantly suppressed protein and mRNA expressions of TNFalpha, IL-6 and ICAM-1 (P0.05) and improved left ventricular function.NF-kappaB activation post CME could upregulate the gene transcriptions of TNFalpha, IL-6, ICAM-1 and enhance inflammatory responses and aggravate left ventricular dysfunction.

To investigate the effects of granulocyte colony stimulating factor (G-CSF) on myocardial apoptosis following coronary microembolization (CME) and possible role of Janus kinase/singnal transducer and activator of transcription (JAK/STAT) pathway in this process.A total of 92 male Sprague Dawley rats were randomized into CME (n = 24), G-CSF (100 microg x kg(-1) x d(-1) i.p. 2 hours post CME for 5 days, n = 24), JAK2 inhibitor AG490 (G-CSF plus AG490, 5 mg x kg(-1) x d(-1) i.p. 2 hours post CME for 5 days, n = 24), all rats received left ventricular injection of homologous microthrombotic particle suspension post clamping the ascending aorta. Sham-operated group (n = 20) served as control. The rats were sacrificed at day 3, 7, 14 and 28 after operation. The myocardial mRNA expressions of Bcl-2, Bax, Fas, FasL and GAPDH which was used as the intercomparison, were evaluated by real time PCR. The ratio of Bcl-2/Bax was compared. The protein expression of Caspase-3, cleaved PARP, t-JAK2, p-JAK2, t-STAT3 and p-STAT3 were detected by western blot. Myocardial apoptosis were examined by TUNEL staining.Compared with Sham rats, the mRNA of Bcl-2, Bax, Fas and FasL significantly increased whereas the ratio of Bcl-2/Bax (0.28 +/- 0.04 vs. 2.98 +/- 0.49) significantly decreased and the protein expression of Caspase-3 (0.762 +/- 0.129 vs. 0.133 +/- 0.027), PARP (0.992 +/- 0.146 vs. 0.386 +/- 0.074) and the myocardial apoptosis index (17.2 +/- 1.9 vs. 1.2 +/- 0.6) significantly increased in CME hearts (all P0.05). rhG-CSF significantly attenuated CME induced changes and cotreatment with JAK2 inhibitor AG490 abolished the effects of rhG-CSF. The protein expressions of t-JAK2 and t-STAT3 among the groups were similar. P-JAK2 and p-STAT3 protein expressions were significantly increased in G-CSF group compared to other groups (P0.05).G-CSF attenuated myocardial apoptosis induced by CME via JAK2/STAT3 pathway.

As a kind of sirolimus-eluting stent (SES) made in China, Firebird SES is more effective than bare metal stent (BMS) and not inferior to Cypher SES for short coronary lesions in terms of reduction of restenosis and revascularization. However, Firebird SES does not show any benefits in patients with a very long coronary lesion (VLCL). The present study was undertaken to evaluate the safety and efficacy of Firebird SES for VLCL by comparison of Cypher SES and BMS.In this prospective, nonrandomized and comparative study, eligible patients with de novo coronary lesion (or = 30 mm) between January 2005 and June 2006 were allocated into Firebird SES group, Cypher SES group or BMS group. They were subjected to an angiographic follow-up of 6 months and a clinical follow-up of 12 months. The primary endpoints constitute the in-stent and in-segment restenosis rates at 6 months. The secondary endpoint was defined as a major adverse cardiovascular event (MACE) that was a 12-month combined endpoint of all-cause deaths, reinfarction or in-stent thrombosis, and target-lesion revascularization. The 12-month in-stent thrombosis was also evaluated to address the safety of Firebird SES implantation exceptionally.A total of 468 patients were assessed for eligibility. Of 113 patients who were finally included according to the prior inclusion and exclusion criteria, 39 (41 lesions) were treated with Firebird SES, 37 (39 lesions) with Cypher SES, and 37 (37 lesions) with BMS. There were no significant differences in the baseline characteristics between the three groups; but there were longer lesions, more frequent use of overlapping stent in the Firebird SES group and the Cypher SES group. Angiographic follow-up showed that the rates of binary stenosis were similar between the Firebird SES group and the Cypher SES group (in-segment: 14.6% vs 12.8%, relative risk (RR) 1.14, P = 0.81; in-stent: 9.8% vs 10.3%, RR 0.95, P = 0.94), and significantly lower than those in the BMS group (in-segment: vs. 36.1%, RR 0.41 or 0.36, P = 0.04 or 0.03, respectively; in-stent: vs 30.6%, RR 0.32 or 0.34, P = 0.03 or 0.04, respectively). The total MACE rate up to 12 months was also similar in both SES groups (7.7% vs 5.4%, P = 1.000), and significantly lower than that in the BMS group (27.0%, P = 0.034 or 0.024, respectively). The in-stent thrombosis rate in the follow-up period was 2.6% in the Firebird SES group, not higher in the Cypher SES and BMS groups (2.7% and 2.7%, respectively, P = 1.000).In the treatment of VLCL, Firebird SES would be safer and more effective than BMS. Firebird SES may be not inferior to Cypher SES in terms of restenosis and MACE.