Nonlinear optical microscopy for skin in vivo:Basics,development and applications

Multi-photon microscopy(MPM)and coherent anti-Stokes Raman scattering(CARS)are two advanced nonlinear optical imaging techniques,which provide complementary information and have great potential in combination for noninvasive in vrito biomedical applications.This paper provides a detailed discussion of the basics,development and applications of these technologies for in vrivo skin research,covering the following topics:The principle and advantage of MPM and CARS,instrumentation development for in vino applications,MPM and CARS of normal skin,application of MPM and CARS in skin cancer and disease diagnosis;application of MPM in skin disease intervention,ie.,imaging guided two-photon photothermolysis.

Clinical application of DNA ploidy to cervical cancer screening: A review

Screening for cervical cancer with DNA ploidy assessment by automated quantitative image cytometry has spread throughout China over the past decade and now an estimated 1 million tests per year are done there. Compared to conventional liquid based cytology, DNA ploidy has competitive accuracy with much higher throughput per technician. DNA ploidy has the enormous advantage that it is an objective technology that can be taught in typically 2 or 3 wk, unlike qualitative cytology, and so it can enable screening in places that lack sufficient qualified cytotechnologists and cytopathologists for conventional cytology. Most papers on experience with application of the technology to cervical cancer screening over the past decade were published in the Chinese language. This review aims to provide a consistent framework for analysis of screening data and to summarize some of the work published from 2005 to the end of 2013. Of particular interest are a few studies comparing DNA ploidy with testing for high risk human papilloma virus(hrH PV) which suggest that DNA ploidy is at least equivalent, easier and less expensive than hrH PV testing. There may also be patient management benefits to combining hr HPV testing with DNA ploidy. Some knowledge gaps are identified and some suggestions are made for future research directions.

Estrogens in males: what have we learned in the last 10 years?

This review focuses on the role of estrogen in men, mainly in male reproduction. The continuing increase in data obtained, and recent discoveries in this area will enable a better understanding of male physiology; these, in turn, will have important clinical implications.

Percutaneous assist devices in acute myocardial infarction with cardiogenic shock: Review, meta-analysis

AIM: To assess the impact of percutaneous cardiac support in cardiogenic shock(CS) complicating acute myocardial infarction(AMI), treated with percutaneous coronary intervention. METHODS: We selected all of the studies published from January 1st, 1997 to May 15 st, 2015 that compared the following percutaneous mechanical support in patients with CS due to AMI undergoing myocardial revascularization:(1) intra-aortic balloon pump(IABP) vs Medical therapy;(2) percutaneous left ventricular assist devices(PLVADs) vs IABP;(3) complete extracorporeal life support with extracorporeal membrane oxygenation(ECMO) plus IABP vs IABP alone; and(4) ECMO plus IABP vs ECMO alone, in patients with AMI and CS undergoing myocardial revascularization. We evaluated the impact of the support devices on primary and secondary endpoints. Primary endpoint was the inhospital mortality due to any cause during the same hospital stay and secondary endpoint late mortality at 6-12 moof follow-up. RESULTS: One thousand two hundred and seventytwo studies met the initial screening criteria. After detailed review, only 30 were selected. There were 6 eligible randomized controlled trials and 24 eligible observational studies totaling 15799 patients. We found that the inhospital mortality was:(1) significantly higher with IABP support vs medical therapy(RR = +15%, P = 0.0002);(2) was higher, although not significantly, with PLVADs compared to IABP(RR = +14%, P = 0.21); and(3) significantly lower in patients treated with ECMO plus IABP vs IABP(RR =-44%, P = 0.0008) or ECMO(RR =-20%, P = 0.006) alone. In addition, Trial Sequential Analysis showed that in the comparison of IABP vs medical therapy, the sample size was adequate to demonstrate a significant increase in risk due to IABP. CONCLUSION: Inhospital mortality was significantly higher with IABP vs medical therapy. PLVADs did not reduce early mortality. ECMO plus IABP significantly reduced inhospital mortality compared to IABP.

Lentivirus vectors construction of SiRNA targeting interference GPC3 gene and its biological effects on liver cancer cell lines Huh-7

Objective:To build GPC3 gene short hairpin interference RNA(shRNA)slow virus veclor.observe expression of Huh-7 GPC3 gene in human liver cell line proliferation apoptosis and the effect of GPC3 gene influencing on liver cancer cell growth,and provide theoretical basis for genc therapy of liver cancer.Methods:Hepatocellular carcinoma cell line Huh-7 wsa transfected by a RNA interference technique.GPC3 gene expression in a variety of liver cancer cell lines was detected by fluorescence quantitative PCR.Targeted GPC3 gene seqnences of small interfering RNA(siRNA)PGC-shRNA-GPC3 were restructured.Stable expression cell linse of siRNA were screened and established with the heplp of liposomes(lipofectamine^(TM2000))as carrier transfcetion of human liver cell lines.In order to validate siRNA interference efficiency.GPC3 siRNA mRNA expression was detected after transfection by using RT-PCR and Western blot.The absorbance value of the cells of blank group,untransfection group and transfection group,the cell cycle and cell apoptosis were calculated,and effects of GPC3 gene nn Huh-7 cell proliferation and apoptosis were observed.Results:In the liver cancer cell lines Huh-7 GPC3 gene showed high expression.PGC-shRNA-GPC3 recombinant plasmid was constructde successfully via sequencing validation.Stable recombinant plasmid transfected into liver cancer cell linse Huh-7can obviously inhibit GPC3 mRNA expression level.Conclusions:The targeted GPC3 siRNA can effectively inhibit the expression of GPC3.

Novel rechargeable calcium phosphate nanoparticle-containing orthodontic cement

White spot lesions （WSLs）, due to enamel demineralization, occur frequently in orthodontic treatment. We recently developed a novel rechargeable dental composite containing nanoparticles of amorphous calcium phosphate （NACP） with long-term calcium （Ca） and phosphate （P） ion release and caries-inhibiting capability. The objectives of this study were to develop the first NACP- rechargeable orthodontic cement and investigate the effects of recharge duration and frequency on the efficacy of ion re-release. The rechargeable cement consisted of pyromellitic glycerol dimethacrylate （PMGDM） and ethoxylated bisphenol A dimethacrylate （EBPADMA）. NACP was mixed into the resin at 40% by mass. Specimens were tested for orthodontic bracket shear bond strength （SBS） to enamel, Ca and P ion initial release, recharge and re-release. The new orthodontic cement exhibited an SBS similar to commercial orthodontic cement without CaP release （P〉 0.1）. Specimens after one recharge treatment （e.g., 1 min immersion in recharge solution repeating three times in one day, referred to as ＂1 min 3 times＂） exhibited a substantial and continuous re-release of Ca and P ions for 14 days without further recharge. The ion re-release did not decrease with increasing the number of recharge/re-release cycles （P〉 0.1）. The ion re-release concentrations at 14 days versus various recharge treatments were as follows： 1 min 3 times〉3 min 2 times〉 1 min 2 times〉6 min 1 time〉3 min 1 time〉 1 min 1 time. In conclusion, although previous studies have shown that NACP nanocomposite remineralized tooth lesions and inhibited caries, the present study developed the first orthodontic cement with Ca and P ion recharge and long-term release capability. This NACP-rechargeable orthodontic cement is a promising therapy to inhibit enamel demineralization and WSLs around orthodontic brackets.

Biointerface engineering nanoplatforms for cancer-targeted drug delivery

Over the past decade,nanoparticle-based therapeutic modalities have become promising strategies in cancer therapy.Selective delivery of anticancer drugs to the lesion sites is critical for elimination of the tumor and an improved prognosis.Innovative design and advanced biointerface engineering have promoted the development of various nanocarriers for optimized drug delivery.Keeping in mind the biological framework of the tumormicroenvironment,biomembrane-camouflaged nanoplatforms have been a research focus,reflecting their superiority in cancer targeting.In this review,we summarize the development of various biomimetic cell membrane-camouflaged nanoplatforms for cancertargeted drug delivery,which are classified according to the membranes fromdifferent cells.The challenges and opportunities of the advanced biointerface engineering drug delivery nanosystems in cancer therapy are discussed.

Composite Configuration Interventional Therapy Robot for the Microwave Ablation of Liver Tumors

The existing interventional therapy robots for the microwave ablation of liver tumors have a poor clinical applicability with a large volume, low positioning speed and complex automatic navigation control. To solve above problems, a composite configuration interventional therapy robot with passive and active joints is developed. The design of composite configuration reduces the size of the robot under the premise of a wide range of movement, and the robot with composite configuration can realizes rapid positioning with operation safety. The cumulative error of positioning is eliminated and the control complexity is reduced by decoupling active parts. The navigation algo- rithms for the robot are proposed based on solution of the inverse kinematics and geometric analysis. A simulation clinical test method is designed for the robot, and the functions of the robot and the navigation algorithms are verified by the test method. The mean error of navigation is 1.488 mm and the maximum error is 2.056 mm, and thepositioning time for the ablation needle is in 10 s. The experimental results show that the designed robot can meet the clinical requirements for the microwave ablation of liver tumors. The composite configuration is proposed in development of the interventional therapy robot for the microwave ablation of liver tumors, which provides a new idea for the structural design of medical robots.

100-nm T-gate InAlAs/InGaAs InP-based HEMTs with f_T = 249 GHz and f_(max) = 415 GHz

InA1As/InGaAs high electron mobility transistors （HEMTs） on an InP substrate with well-balanced cutoff frequency fT and maximum oscillation frequency frnax are reported. An InA1As/InGaAs HEMT with 100-nm gate length and gate width of 2 × 50 μm shows excellent DC characteristics, including full channel current of 724 mA/mm, extrinsic maximum transconductance gm.max of 1051 mS/mm, and drain-gate breakdown voltage BVDG of 5.92 V. In addition, this device exhibits fT = 249 GHz and fmax = 415 GHz. These results were obtained by fabricating an asymmetrically recessed gate and minimizing the parasitic resistances. The specific Ohmic contact resistance was reduced to 0.031 0.mm. Moreover, the fT obtained in this work is the highest ever reported in 100-nm gate length InA1As/InGaAs InP-based HEMTs. The outstanding gm.max, fT, fmax, and good BVDG make the device suitable for applications in low noise amplifiers, power amplifiers, and high speed circuits.

Calcium phosphate cements for bone engineering and their biological properties

Calcium phosphate cements （CPCs） are frequently used to repair bone defects. Since their discovery in the 1980s, extensive research has been conducted to improve their properties, and emerging evidence supports their increased application in bone tissue engineering. Much effort has been made to enhance the biological performance of CPCs, including their biocompatibility, osteoconductivity, osteoinductivity, biodegradability, bioactivity, and interactions with cells. This review article focuses on the major recent developments in CPCs, including 3D printing, injectability, stem cell delivery, growth factor and drug delivery, and pre- vascularization of CPC scaffolds via co-culture and tri-culture techniques to enhance angiogenesis and osteogenesis.

Effects of Si δ-Doping Condition and Growth Interruption on Electrical Properties of InP-Based High Electron Mobility Transistor Structures

The InGaAs/InAIAs/InP high electron mobility transistor （HEM：F） structures with lattice-matched and pseudo- morphic channels are grown by gas source molecular beam epitaxy. Effects of Si ^-doping condition and growth interruption on the electrical properties are investigated by changing the Si-cell temperature, doping time and growth process. It is found that the optimal Si ^-doping concentration （Nd） is about 5.0 x 1012 cm-2 and the use of growth interruption has a dramatic effect on the improvement of electrical properties. The material structure and crystal interface are analyzed by secondary ion mass spectroscopy and high resolution transmission elec- tron microscopy. An InGaAs/InAiAs/InP HEMT device with a gate length of lOOnm is fabricated. The device presents good pinch-off characteristics and the kink-effect of the device is trifling. In addition, the device exhibits fT = 249 GHa and fmax 〉 400 GHz.

A preliminary report on adjuvant analgesic efficacy of HANS in opioid tolerant patients with cancer pain

Objective： To observe the adjuvant analgesic efficacy of Han＇s Acupoint Nerve Stimulator （HANS） in opioid tolerant patients with cancer pain. Methods： A prospective non-controlled study was conducted. Opioid tolerant patients with cancer pain were enrolled and treated with both routinely analgesics and adjuvant HANS （2/100 Hz for 30 min/d, 5 d on and 2 d off for two weeks）. Cancer pain, quality of life （QOL）, anxiety and depression were assessed before enrollment and on d 8 and d 15 with the BPI-C, EORTC QLQ-C30, and self-rating anxiety scale （SAS）/ self-rating depression scale （SDS）, respectively; the therapeutic frequency of breakthrough pain （BP） and daily opioid dose were also recorded. Results： Totally 47 patients meeting the inclusion criteria participated in this study; 43 patients completed the two-week treatment and assessment. The mean scores of patient＇s ＂worst＂ and ＂least＂ pain intensity assessed with BPI-C decreased significantly on d 8 and d 15; the therapeutic frequency of BP also significantly decreased; but the average daily dose of opioids did not change significantly. For the nine symptoms in EORTC QLQ-C30 assessment, the mean scores of pain, fatigue, constipation and insomnia were significantly lower on d 8 and d 15 compared with baseline; the mean scores of the overall health status, nausea/vomiting and the incidence rates of both anxiety and depression also decreased significantly on d 15. Conclusions： To opioid tolerant patients with cancer pain, adjuvant treatment with HANS could improve pain release and patients＇ QOL by decreasing the severity of pain, fatigue, constipation, insomnia and other concomitant symptoms; it could also decrease the incidence rates of anxiety and depression.

Improvement of breakdown characteristics of an A1GaN/GaN HEMT with a U-type gate foot for millimeter-wave power application

In this study, the physics-based device simulation tool Silvaco ATLAS is used to characterize the electrical properties of an AlGaN/GaN high electron mobility transistor （HEMT） with a U-type gate foot. The U-gate AlGaN/GaN HEMT mainly features a gradually changed sidewall angle, which effectively mitigates the electric field in the channel, thus obtaining enhanced off-state breakdown characteristics. At the same time, only a small additional gate capacitance and decreased gate resistance ensure excellent RF characteristics for the U-gate device. U-gate AlGaN/GaN HEMTs are feasible through adjusting the etching conditions of an inductively coupled plasma system, without introducing any extra process steps. The simulation results are confirmed by experimental measurements. These features indicate that U-gate A1GaN/GaN HEMTs might be promising candidates for use in millimeter-wave power applications.

Improved image resolution on thoracic carcinomas by quantitative 18F-FDG coincidence SPECT/CT in comparison to 18F-FDG PET/CT

Currently,18F-FDG coincidence SPECT(Co-SPECT)/CT scan still serves as an important tool for diagnosis,staging,and evaluation of cancer treatment in developing countries.We implemented full physical corrections(FPC) to Co-SPECT(quantitative Co-SPECT) to improve the image resolution and contrast along with the capability for image quantitation.FPC included attenuation,scatter,resolution recovery,and noise reduction.A standard NEMA phantom filled with 10:1 F-18 activity concentration ratio in spheres and background was utilized to evaluate image performance.Subsequently,15 patients with histologically confirmed thoracic carcinomas were included to undergo a 18 F-FDG Co-SPECT/CT scan followed by a 18 F-FDG PET/CT scan.Functional parameters as SUVmax,SUVmean,SULpeak,and MTV from both quantitative Co-SPECT and PET were analyzed.Image resolution of Co-SPECT for NEMA phantom was improved to reveal the smallest sphere from a diameter of 28 mm to 22 mm(17 mm for PET).The image contrast was enhanced from 1.7 to 6.32(6.69 for PET) with slightly degraded uniformity in background(3.1% vs.6.7%)(5.6% for PET).Patients’ SUVmax,SUVmean,SULpeak,and MTV measured from quantitative Co-SPECT were overall highly correlated with those from PET(r=0.82-0.88).Adjustment of the threshold of SUVmax and SUV to determine SUVmean and MTV did not further change the correlations with PET(r=0.81-0.88).Adding full physical corrections to Co-SPECT images can significantly improve image resolution and contrast to reveal smaller tumor lesions along with the capability to quantify functional parameters like PET/CT.

Safety Evaluation of Stacked Genetically Modified Corn Event (MON89034 ×MON88017) Using Zebrafish as an Animal Model

This study assessed the effect of feeding stacked genetically modified (GM) corn event (MON89034 × MON88017) on embryonic development, adult tissue histology and assessed the possibility of transgenic DNA transfer, using zebrafish as an animal model. Adult zebrafish were separated into male and female groups. After 3 weeks of feeding with experimental diets, males and females were paired once a week and fertilized embryos were collected, then the male and female fish were re-turned to their sex-specific groups. This fertilization and embryo collection process were repeated 3 times. Embryonic morphological measurements were obtained on developing embryos up to 96 hours after fertilization, and then the embryos were fixed in 4% phosphate-buffered paraformal-dehyde for morphologic assessment. At the end of the feeding study, various adult zebrafish tissues were histologically examined for abnormalities. Both zebrafish tissues and embryos were analyzed for presence of plant specific genes and transgenic sequences. No changes or abnormalities were observed in embryonic morphology nor in any of the tissues examined histologically. In addition, no plant DNA reference genes or transgenic DNA were found in any of the analyzed samples. These results demonstrate that the safety and nutrition of MON89034 × MON88017 corn are similar to non-GM corn.

Function of the CaMKII-ryanodine receptor signaling pathway in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia

BACKGROUND:Calcium calmodulin-dependent kinase II(CaMKII) can be more active in patients with left ventricular hypertrophy(LVH),which in turn causes phosphorylation of ryanodine receptors,resulting in inactivation and the instability of intracellular calcium homeostasis.The present study aimed to determine the effect of CaMKII-ryanodine receptor pathway signaling in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia.METHODS:Forty New Zealand rabbits were randomized into four groups(10 per group):sham group,LVH group,KN-93 group(LVH+KN-93),and ryanodine group(LVH+ryanodine).Rabbits in the LVH,KN-93,and ryanodine groups were used to establish a left ventricular hypertrophy model by the coarctation of the abdominal aorta,while those in the sham group did not undergo the coarctation.After eight weeks,action potentials(APs) were recorded simultaneously in the endocardium and epicardium,and a transmural electrocardiogram(ECG) was also recorded in the rabbit left ventricular wedge model.Drugs were administered to the animals in the KN-93 and ryanodine groups,and the frequency of triggered APs and ventricular tachycardia was recorded after the rabbits were given isoprenaline(1 μmol/L) and high-frequency stimulation.RESULTS:The frequency(animals/group) of triggered APs was 0/10 in the sham group,10/10 in the LVH group,4/10 in the KN-93 group,and 1/10 in the ryanodine group.The frequencies of ventricular tachycardia were 0/10,9/10,3/10,and 1/10,respectively.The frequencies of polymorphic ventricular tachycardia or ventricular fibrillation were 0/10,7/10,2/10,and 1/10,respectively.The frequencies of triggered ventricular arrhythmias in the KN-93 and ryanodine groups were much lower than those in the LVH group(P<0.05).CONCLUSIONS:KN-93 and ryanodine can effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH.The CaMKII-ryanodine signaling pathway can be used as a new means of treating ventricular arrhythmia.

H2 Production from Wind Power in a Wind Farm in Spain

A hydrogen production and conversion plant from wind power was installed in the Sotavento wind farm by Gas Natural and the Galician Government. This facility is the highest electrolysis power installed at the European level. It consists of an electrolyser of 300 kW, a piston compressor, a 1,725 Nm3 H2 storage system and an engine of 55 kW. This pilot plant is being operated by Natural Gas in order to extrapolate its behavior to that of an industrial facility capable of managing all the production of Sotavento wind farm following different strategies： balancing, peak-shaving and repowering. In this paper, preliminary results at the facility are presented. The aim of these first tests has been to describe the operation of equipment under operating conditions required in the management of wind power production, in order to understand the behavior of the different equipment and try to make them suitable for this type of applications. This paper shows the difficulty of operating these systems under the wind power requirements.

Prognostic role of ABO blood type in patients with extranodal natural killer/T cell lymphoma,nasal type:a triple.center study

Background:The prognostic significance of ABO blood type for lymphoma is largely unknown.We evaluated the prognostic role of ABO blood type in patients with extranodal natural killer(NK)/T-cell lymphoma(ENKTL).Methods:We retrospectively analyzed clinical data of 697 patients with newly diagnosed ENKTL from three cancer centers.The prognostic value of ABO blood type was evaluated using Kaplan-Meier curves and Cox proportional hazard models.The prognostic values of the International Prognostic Index(IPI) and the Korean Prognostic Index(KPI)were also evaluated.Results:Compared with patients with blood type O,those with blood type non-O tended to display elevated baseline serum C-reactive protein levels(P=0.038),lower rate of complete remission(P=0.005),shorter progression-free survival(PFS,P<0.001),and shorter overall survival(OS,P=0.001).Patients with blood type O/AB had longer PFS(P<0.001) and OS(P=0.001) compared with those with blood type A/B.Multivariate analysis demonstrated that age >60 years(P<0.001),mass ≥5 cm(P=0.001),stage Ⅲ/Ⅳ(P<0.001),elevated serum lactate dehydrogenase(LDH) levels(P=0.001),and blood type non-O were independent adverse predictors of OS(P=0.001).ABO blood type was found to be superior to both the IPI in discriminating patients with different outcomes in the IPI low-risk group and the KPI in distinguishing between the intermediate-to-low-and high-to-intermediate-risk groups.Conclusions:ABO blood type was an independent predictor of clinical outcome for patients with ENKTL.

Extrinsic Base Surface Passivation in High Speed ＂Type-II＂ GaAsSb/InP DHBTs Using an InGaAsP Ledge Structure

Type-II GaAsSb/InP DHBTs with selectively-etched InGaAsP ledge structures are fabricated and characterized for the first time. The novel InGaAsP/GaAsSb/InP DHBTs with a 20nm lattice-matched GaAsSb base and a 75 nm InP collector have a dc current gain improvement by a factor of 2 and a cutoff frequency fT of 190 GHz. The InGaAsP ledge design provides a simple but effective approach to suppress the extrinsic base surface recombination and enable GaAsSb/InP DHBTs to further increase the operating frequencies and integration levels for millimeter wave applications.

A Posteriori Error Estimates for Finite Element Methods for Systems of Nonlinear,Dispersive Equations

The present study regards the numerical approximation of solutions of systems of Korteweg-de Vries type,coupled through their nonlinear terms.In our previous work[9],we constructed conservative and dissipative finite element methods for these systems and presented a priori error estimates for the semidiscrete schemes.In this sequel,we present a posteriori error estimates for the semidiscrete and fully discrete approximations introduced in[9].The key tool employed to effect our analysis is the dispersive reconstruction devel-oped by Karakashian and Makridakis[20]for related discontinuous Galerkin methods.We conclude by providing a set of numerical experiments designed to validate the a posteriori theory and explore the effectivity of the resulting error indicators.