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Electromagnetic turbulence and ion kinetics in counterstreaming plasmas hold great significance in laboratory astrophysics, such as turbulence field amplification and particle energization. Here, we quantitatively demonstrate for the first time how electromagnetic turbulence affects ion kinetics under achievable laboratory conditions (millimeter-scale interpenetrating plasmas with initial velocity of 2000 km/s, density of 4×10^{19} cm^{-3}, and temperature of 100 eV) utilizing a recently developed high-order implicit particle-in-cell code without scaling transformation. It is found that the electromagnetic turbulence is driven by ion two-stream and filamentation instabilities. For the magnetized scenarios where an applied magnetic field of tens of Tesla is perpendicular to plasma flows, the growth rates of instabilities increase with the strengthening of applied magnetic field, which therefore leads to a significant enhancement of turbulence fields. Under the competition between the stochastic acceleration due to electromagnetic turbulence and collisional thermalization, ion distribution function shows a distinct super-Gaussian shape, and the ion kinetics are manifested in neutron yields and spectra. Our results have well explained the recent unmagnetized experimental observations, and the findings of magnetized scenario can be verified by current astrophysical experiments.
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PURPOSE: Five strategies were recommended by the American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) guidelines for the treatment of postmenopausal osteoporosis (PMO) patients with a very high fracture risk. We aimed to assess their cost-effectiveness in the United States (US). METHODS: A microsimulation Markov model was created to compare the cost-effectiveness of five treatment strategies, including zoledronate, denosumab, abaloparatide, teriparatide, and romosozumab in PMO patients with a recent fracture from the healthcare perspective of the US. The data used in the model were obtained from published studies or online resources. Base-case analysis, one-way deterministic sensitivity analysis (DSA) and probability sensitivity analysis (PSA) were conducted for 65-, 70-, 75-, and 80-year-old patients. RESULTS: In base case, at 65 years, zoledronate was the cheapest strategy. The incremental cost-effectiveness ratios (ICER, which represent incremental costs per QALY gained) of denosumab, teriparatide, abaloparatide, and romosozumab against zoledronate were $13,020/QALY (quality-adjusted years), $477,331 /QALY, $176,287/QALY, and $98,953/QALY, respectively. Under a willing-to-pay (WTP, which means the highest price a consumer will pay for one unit of a good of service) threshold of $150,000/QALY, denosumab and romosozumab were cost-effective against zoledronate. The PSA results showed that denosumab was the most cost-effective option with WTP thresholds of $50,000/QALY, $100,000/QALY and $150,000/QALY. The results were similar in other age groups. The DSA results indicated that the most common parameters that have important influence on the outcome were drug persistence, incidence of adverse events, the efficacy of drugs on hip fractures and the cost of the drug. CONCLUSION AND RELEVANCE: Among PMO patients with a very high fracture risk in the US, zoledronate is the cheapest strategy and denosumab is the most cost-effective choice among these five strategies.
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Conservadores de la Densidad Ósea , Fracturas de Cadera , Osteoporosis Posmenopáusica , Osteoporosis , Humanos , Femenino , Estados Unidos/epidemiología , Conservadores de la Densidad Ósea/uso terapéutico , Teriparatido/uso terapéutico , Denosumab/uso terapéutico , Ácido Zoledrónico/uso terapéutico , Análisis de Costo-Efectividad , Posmenopausia , Análisis Costo-Beneficio , Osteoporosis/tratamiento farmacológico , Osteoporosis Posmenopáusica/tratamiento farmacológico , Osteoporosis Posmenopáusica/epidemiologíaRESUMEN
The efficiency of high-order harmonic generation from a relativistic laser interacting with solid targets depends greatly on surface plasma distribution. The usual method of enhancing efficiency involves tuning the plasma scale length carefully by improving the laser contrast. Here, we experimentally demonstrate that efficient harmonics can be achieved directly by compressing large-scale surface plasma via the radiation pressure of a circularly polarized normally incident prepulse. The harmonic generation efficiency obtained by this method is comparable to that obtained with optimized plasma scale length by high-contrast lasers. Our scheme does not rely on high-contrast lasers and is robust and easy to implement. Thus, it may pave a way for the development of intense extreme ultraviolet sources and future applications with high repetition rates.
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OBJECTIVE: To compare the therapeutic efficacy of paclitaxel (PTX) alone to its combination with methotrexate (MTX) on rheumatoid arthritis. METHODS: A collagen-induced arthritis (CIA) rat model was established by induction of type II collagen. Rats were divided into blank control group, CIA model group, MTX group 1â¯mg/kg, PTX 1.5â¯mg/kg, PTX 2.5â¯mg/kg, PTX 3.5â¯mg/kg, and MTX 1â¯mg/kgâ¯+ PTX 3.5â¯mg/kg, with 10 rats per group. The inflammation of the ankle joint was analyzed by H&E staining and interleukin (IL)-1ß and IL6 expression was detected by immunohistochemistry. TUNEL assay was performed to detect synovial tissue cell apoptosis after administration of PTX and MTX either alone or in combination. TLR4 and pNF-κBp65 protein expression in synovial tissue and the changes of serum IL1ß, IL6, IL12, MMP3, and TNFα protein factors were detected by western blot and ELISA, respectively. RESULTS: PTX and MTX improved histopathological changes in CIA rats. Besides, the apoptosis rate of synovial tissue cells in the PTX 3.5â¯mg/kg group was more than that of the PTXâ¯+ MTX group. Immunohistochemistry and western blot results indicated that PTX and MTX reduce the expression rate of IL6 and IL1ß and downregulate TLR4 and pNF-κBp65 protein expression. Furthermore, TLR4 and pNF-κBp65 reduced the concentration of MMP3, IL12, IL6, IL1ß, and TNFα. CONCLUSION: Both PTX and MTX exert significant suppression on rheumatoid arthritis, and the combined effect of the two drugs is weaker than that of PTX alone. Moreover, intraperitoneal injection of PTX 3.5â¯mg/kg every other day was the optimal dose observed in this study.
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Artritis Experimental , Artritis Reumatoide , Animales , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/patología , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/patología , Metotrexato/uso terapéutico , Paclitaxel , Ratas , Membrana SinovialRESUMEN
Objective: To assess the efficacy and safety of Saccharomyces boulardii (S. boulardii) in combination with triple therapy as a first-line regimen for the eradication of Helicobacter pylori (H. pylori) in non-ulcer dyspepsia (NUD) patients. Methods: A total of 497 Helicobacter pylori-positive patients who underwent gastroscopy and diagnosed with NUD were enrolled from June 2018 to January 2020 in 9 medical centers across China. Participants were segmentedly randomly divided into 3 groups. Patients in group A received S. boulardii for 14 days and triple therapy for 10 days, while patients in group B received bismuth quadruple group for 10 days, and patients in group C received triple therapy for 10 days. The H. pylori status was determined by the 13C-urea breath test on the 44th day of the treatment. Symptom improvement and adverse reactions were assessed on the 14th and 44th day. Results: There were 229 males and 268 females in all 497 patients enrolled. They were aged 18-69 (46.1±11.8) years and 472 of them (158 cases in group A, 159 cases in group B, and 155 cases in group C) completed the trial. The intention-to-treat (ITT) eradication rates in patients in patients A, B and C were 77.8% (126/162), 80.1% (137/171) and 65.2% (107/164) respectively, and per protocol-based (PP) eradication rates were 79.7% (126/158), 86.2% (137/159) and 69.0% (107/155) respectively. The differences were statistically significant in ITT and PP analysis among 3 groups (ITT: χ²=11.14, P<0.01; PP: χ²=13.86, P<0.01). There was no significant difference between eradication rates of two quadruple therapys(all P>0.05), but both of them were significantly higher than that of standard triple therapy (both P<0.05). Statistics revealed that both quadruple therapys led to significantly higher symptom improvement of belching compared with that of standard triple therapy in day 14 (P<0.05). The relief of abdominal distension and belching symptom scores of group A were significantly higher than those of group C in day 44(all P<0.05). There was no serious adverse event reported. The incidence of diarrhea in group A was significantly lower than those in the other two groups (both P<0.05). Conclusions: The combination of S. boulardii and triple therapy can achieve a better eradication effect on H. pylori infection with NUD, and has advantages in symptom relief and safety.
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Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Saccharomyces boulardii , Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Bismuto/uso terapéutico , Quimioterapia Combinada , Eructación/tratamiento farmacológico , Femenino , Gastritis/tratamiento farmacológico , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Masculino , Resultado del TratamientoRESUMEN
PURPOSE: Despite the large number of osteoporosis patients in China, the diagnosis and treatment rates remain low. The Fracture Risk Assessment Tool (FRAX) can be used to effectively evaluate fracture risk. In this study, we explored the Chinese-specific thresholds of FRAX without the T-score. METHODS: In all, 264 postmenopausal women aged > 50 years were randomly recruited from community-medical centers. All subjects completed self-reported questionnaires, BMD measurements, and spinal radiographs. The 10-year hip and major osteoporotic fracture risks were calculated by FRAX. A new threshold for both 10-year hip and major osteoporotic fracture risk was explored with receiver operating characteristic (ROC) curve analysis. RESULTS: Overall, 92 subjects were diagnosed with osteoporosis. Among them, 14 participants with T-score > - 2.5 were diagnosed with osteoporosis based on clinical fractures. ROC analysis showed the cut-off value of the 10-year hip osteoporotic fracture for detecting osteoporosis was 0.95%, while that of 10-year major osteoporotic fracture was 4.95%. The sensitivity and specificity of the 10-year hip osteoporotic fracture probability for detecting osteoporosis were 0.86 and 0.59, respectively, while the guideline-recommended threshold had a sensitivity of 0.49 and specificity of 0.83. The sensitivity and specificity of the 10-year major osteoporotic fractures with the new threshold were 0.76 and 0.69, respectively, while the recommended threshold had a sensitivity of 0 and specificity of 1. CONCLUSION: Current guideline-recommended FRAX thresholds without BMD showed low sensitivity. Therefore, 10-year osteoporotic hip fracture probability ≥ 0.95% and 10-year osteoporotic major fracture probability ≥ 4.95% are recommended as the new thresholds.
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Densidad Ósea , Osteoporosis Posmenopáusica/diagnóstico , Fracturas Osteoporóticas/diagnóstico , Posmenopausia , Medición de Riesgo/normas , Adulto , Anciano , Anciano de 80 o más Años , China/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Osteoporosis Posmenopáusica/epidemiología , Fracturas Osteoporóticas/epidemiología , Pronóstico , Curva ROC , Estándares de Referencia , Factores de RiesgoRESUMEN
Objectives: To compare the impact of ticagrelor or clopidogrel on serum uric acid levels among patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI) and further evaluate the effects of variation of serum uric acid levels on platelet reactivity. Methods: STEMI patients who admitted to Fuwai Hospital from April 2017 to January 2020, and underwent primary PCI and discharged alive with aspirin and ticagrelor or clopidogrel were included in this study. Patients were divided into ticagrelor group and clopidogrel group. The baseline clinical data were collected. Serum uric acid and creatinine levels at baseline and 30 days post-PCI were measured. Light transmittance aggregometry was used to assess maximum aggregation rate induced by adenosine diphosphate and arachidonic acid. The changes of serum uric acid and creatinine were compared between the two groups. Multivariate logistic regression was performed to evaluate independent related factors for rise in the uric acid levels, and the effect of variation of serum uric acid level on platelet reactivity was analyzed. Results: A total of 967 patients were included, the age was (59.4±12.1) years, and 163 case were female. There were 550 cases in ticagrelor group (56.9%) and 417 cases in clopidogrel group (43.1%). Baseline serum uric acid and creatinine levels were similar between the 2 groups. At 30 days, the serum uric acid level [(347.2±96.5) mmol/L vs. (341.2±105.3) mmol/L, P=0.009] and absolute [46.4 (-2.4, 88.1) mmol/L vs. 25.0 (-21.9, 73.0) mmol/L, P=0.001] and percentage [13.2 (-0.01, 29.0) % vs. 7.9 (-5.7, 25.0) %, P=0.007] increase in the serum uric acid levels were significantly higher in ticagrelor group than in clopidogrel group. The level of serum creatinine at 30 days was significantly lower in ticagrelor group than in clopidogrel group [(89.7±21.3) µmol/L vs. (94.4±43.9) µmol/L, P<0.05], whereas there were no differences in absolute [8.0 (-1.4, 16.6) µmol/L vs. 7.8 (-2.0, 16.6) µmol/L] and percentage [10.5 (-1.7%, 22.6%) vs. 9.8 (-2.4%, 22.1%)] change in the serum creatinine between the 2 groups (all P>0.05). Logistic regression analysis showed that, after adjusting for confounding factors, ticagrelor therapy was an independent related factor of serum uric acid elevation (OR=1.582, 95% CI:1.023-2.447, P=0.039). The variation of the serum uric acid levels did not affect platelet aggregation and the percentage of high platelet reactivity in both groups. Conclusions: Ticagrelor use is related to a significant increase in the serum uric acid levels at 30 days post-PCI in this patient cohort. The variations in the uric acid levels do not increase the percentage of high platelet reactivity in STEMI patients treated with ticagrelor or clopidogrel.
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Infarto del Miocardio , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Adenosina/uso terapéutico , Anciano , Femenino , Humanos , Persona de Mediana Edad , Infarto del Miocardio/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ticagrelor/uso terapéutico , Ticlopidina , Factores de Tiempo , Resultado del Tratamiento , Ácido ÚricoRESUMEN
ABSTRACT: Objective To establish a method for determination of the azide ions in blood by gas chromatography-mass spectrometry ï¼GC-MSï¼ following pentafluorobenzyl derivatization. Methods A blood sample of 0.2 mL was placed into a 10 mL glass test tube, and the internal standard sodium cyanide, derivatization reagent pentafluorobenzyl bromide and catalyst tetradecyl benzyl dimethyl ammonium chloride were added in turn. After vortex mixing, the mixture was heated with low-power microwave for 3 min. After centrifugation, the organic phase was taken for GC-MS analysis. Results The azide ions in blood had a good linear relationship in the mass concentration range of 0.5 to 20 µg/mL. The lowest detection limit was 0.25 µg/mL and the relative recovery was 91.36%-94.58%. The method was successfully applied to a case of death from sodium azide poisoning. The mass concentration of azide ions in the blood of the dead was 11.11 µg/mL. Conclusion The method developed in this paper has strong specificity and is easy to operate, which is suitable for the rapid detection of azide ions in blood.
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Azidas , Cromatografía de Gases y Espectrometría de Masas , Humanos , IonesRESUMEN
OBJECTIVE: To identify the role of misshapen/NIK-related kinase (MINK1) in age-related Osteoarthritis (OA) and injury-induced OA, and the effects of enhanced TGFß signaling in these progresses. DESIGN: The effect of MINK1 was analyzed with MINK1 knock out (Mink1-/-) mice and C57BL/6J mice. OA progress was studied in age-related OA and instability-associated OA (destabilization of the medial meniscus, DMM) models. The murine knee joint was evaluated through histological staining, Osteoarthritis Research Society International (OARSI) scores, immunohistochemistry, and µCT analysis. Primary chondrocytes were isolated from wild type and Mink1-/- mice and subjected to osteogenic induction and Western blot analysis. RESULTS: MINK1 is highly expressed during cartilage development and in normal cartilage. Mink1-/- mice displayed markedly lower OARSI scores, aggrecan degradation neoepitope positive cells and increased Safranin O and pSMAD2 staining in aging-related OA model. However, in injury-induced OA, loss of MINK1 accelerates extracellular matrix (ECM) destruction, osteophyte formation, and subchondral bone sclerosis. Accelerated subchondral bone remodeling in Mink1-/- mice was accompanied with increased numbers of nestin-positive mesenchymal stem cells (MSCs) and osterix-positive osteoprogenitors. pSMAD2 staining was increased in the subchondral bone marrow of Mink1-/- mice and overexpression of MINK1 inhibited SMAD2 phosphorylation in vitro. CONCLUSIONS: This study shows for the first time that activation of TGFß/SMAD2 by MINK1 deficiency plays opposite roles in aging-related and injury-induced OA. MINK1 deficiency protects cartilage from degeneration in aging joints through increased SMAD2 activation in chondrocytes, while accelerating OA progress in injury-induced model through enhanced osteogenesis of MSCs in the subchondral bone. These findings provide insights for developing precision OA therapeutics targeting TGFß/SMAD2 signaling.
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Osteoartritis/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Animales , Western Blotting , Células Cultivadas , Condrocitos/metabolismo , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Articulaciones/diagnóstico por imagen , Articulaciones/patología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Osteoartritis/diagnóstico por imagen , Osteoartritis/patología , Osteogénesis , Transducción de Señal , Microtomografía por Rayos XRESUMEN
Objectives: To investigate whether the fecal microbiome of Parkinson's disease patients differs from that of healthy population and explore the pathogenesis and new treatment of idiopathic Parkinson's disease. Methods: A total of 30 patients diagnosed as idiopathic Parkinson disease (PD group) in Beijing Friendship Hospital between April 2017 and June 2018 were enrolled and 30 healthy controls (NC group) were recruited at the same time.Medical records and score of unified Parkinson's disease rating scale (UPDRS) were collected and fresh fecal samples were obtained and stored in refrigerator (-80â). The microbial compositions of fecal samples were investigated by 16S rRNA gene sequencing targeting the V3-V4 region. The taxa abundance and microbial composition were tested. Results: There was no difference of age and sex in PD and NC groups. Chao1 and Shannon indexes tended to be higher in PD group, yet failed to reach statistic significance (P=0.115 and 0.052). Relative abundance of gut microbiota differed in each taxonomic category. The relative abundance of Firmicutes in PD group was 53.6%(41.7%-64.8%), while that of Bacteroidetes in NC group was 51.7%(31.7%-65.3%). The ratios of Firmicutes to Bacteroidetes were significantly different between the two groups (1.6(0.9-3.4) vs 0.7(0.5-1.4), P=0.001). In Clostridia, Bacilli and Erysipelotrichia of Firmicutes, the relative abundances of Clostridiales, Christensenellaceae, Peptoclostridium, Lactobacillus and Erysipelatoclostridium were higher in PD group (P=0.024, 0.046, 0.036, 0.022 and 0.037). The relative abundance of Prevotella of Bacteroidales, was lower in PD group, yet failed to reach statistic significance (P=0.121). The relative abundances of Alistipes of Rikenellaceae and Butyricimonas of Marinilabiliales in PD group were significantly higher than those in NC group (P=0.047 and 0.033). The relative abundance of Bifidobacterium of Actinobacteria was significanly higher in PD group when compared with NC group (P=0.009). Despite the relatively low abundance, Akkermansia of Verrucomicrobia was significantly higher in PD group than in NC group (P=0.025). Conclusion: The structures of the fecal microbiota differ significantly between PD patients and healthy controls.
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Microbioma Gastrointestinal , Enfermedad de Parkinson , Heces , Humanos , ARN Ribosómico 16SRESUMEN
Objective: To investigate the association between postprocedural D-dimer, high sensitivity C-reactive protein(hs-CRP) and low-density lipoprotein-cholesterol(LDL-C) and outcomes of acute myocardial infarction (AMI) patients treated by percutaneous coronary intervention(PCI), in order to clarify the impacts of thrombotic, inflammatory and cholesterol risks on long-term prognosis. Methods: Patients with AMI who underwent emergency PCI from January 2010 to June 2017 in Fuwai Hospital with complete baseline data were enrolled. Patients were stratified into four groups according to quartiles of D-dimer, hs-CRP and LCL-C. Cox regression was used to analyze the relationship between these biomarkers and prognosis. Restricted cubic spline (RCS) was used to characterize the continuous association between risk of all-cause death and biomarkers. The primary outcome was all-cause death. Results: A total of 3 614 patients were included in the analysis. The age was (59.2±12.0) years old, and 2 845 (78.7%) were male and 3 161 (87.5%) patients were diagnosed as ST-segment elevation myocardial infarction. The follow-up time was 652 (414, 1 880) days. Survival analysis showed that postprocedural D-dimer and hs-CRP were significantly associated with all-cause mortality (all P<0.05). Cox regression with multiple adjustments showed that patients with D-dimer≥580 µg/L presented higher risk of all-cause death (HR=2.03, 95%CI 1.22-3.38, P=0.006), compared to patients with D-dimer<220 µg/L. RCS analysis showed that risk of all-cause death was stably high when D-dimer reached 500 µg/L. Multivariable Cox regression also showed that patients with hs-CRP<2.74 mg/L (HR=1.86, 95%CI 1.10-3.15, P=0.020)or hs-CRP≥11.99 mg/L (HR=2.14, 95%CI 1.35-3.40, P=0.001) presented higher mortality compared to patients whose hs-CRP was 2.74-7.18 mg/L. RCS analysis indicated a J-shaped relation between hs-CRP and mortality, as greater risk of death was observed when hs-CRP was lower than 2 mg/L or higher than 10 mg/L. LDL-C was not associated with outcomes (all P>0.05). Conclusions: Postprocedural D-dimer is significantly associated with long-term prognosis of AMI patients treated by PCI. Patients with extremely high or low levels of hs-CRP presents worse outcomes. Intensive and tailored antithrombotic or anti-inflammatory therapies should be considered for patients with increased thrombotic risk and those with extremely high or low inflammatory risk.
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Infarto del Miocardio , Intervención Coronaria Percutánea , Anciano , Biomarcadores , Proteína C-Reactiva , LDL-Colesterol , Femenino , Productos de Degradación de Fibrina-Fibrinógeno , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/cirugía , PronósticoRESUMEN
Objective: To compare the 6-month follow-up results of primary percutaneous coronary intervention (PPCI) guided by optical coherence tomography (OCT) or coronary angiography (CAG) alone in a larger ST-segment elevation myocardial infarction (STEMI) cohort. Methods: We enrolled 275 STEMI patients undergoing OCT-guided PPCI from March 2017 through December 2018. Two hundred and seventy-five propensity score matched STEMI patients undergoing CAG-guided PPCI served as control group. The 6-month clinical follow-up results were compared between the two groups. The demographic data, complications, coronary angiography and OCT characteristics were evaluated. Results: OCT evaluation showed that there were 151 patients (54.9%) with plaque prolapse and 113 patients (41.1%) with stent malposition. Proximal and/or distal dissection of stents occurred in 38 patients (13.8%), of which 3 patients (1.1%) had both proximal and distal dissection. Of the 38 patients, 2 patients received rescue stent implantation. Results of clinical follow-up at 6 months showed that there was no significant difference in cardiovascular death, repeat myocardial infarction, target vessel revascularization, stroke and hemorrhage endpoint events between OCT-guided PPCI patients and CAG-guided PPCI patients (P=0.682). Conclusion: Clinical events at 6 months are similar between OCT-guided PPCI and CAG-guided PPCI for STEMI patients.
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Intervención Coronaria Percutánea , Tomografía de Coherencia Óptica , Angiografía Coronaria , Estudios de Seguimiento , Humanos , Resultado del TratamientoRESUMEN
The 'Trojan Horse' underdense plasma photocathode scheme applied to electron beam-driven plasma wakefield acceleration has opened up a path which promises high controllability and tunability and to reach extremely good quality as regards emittance and five-dimensional beam brightness. This combination has the potential to improve the state-of-the-art in accelerator technology significantly. In this paper, we review the basic concepts of the Trojan Horse scheme and present advanced methods for tailoring both the injector laser pulses and the witness electron bunches and combine them with the Trojan Horse scheme. These new approaches will further enhance the beam qualities, such as transverse emittance and longitudinal energy spread, and may allow, for the first time, to produce ultrahigh six-dimensional brightness electron bunches, which is a necessary requirement for driving advanced radiation sources. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.
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ABSTRACT: Objective To identify tiletamine, zolazepam and their metabolites in samples from drug facilitated sexual assault by gas chromatography-quadrupole time of flight mass spectrometry ï¼GC-QTOF-MSï¼. Methods Urine samples of victims were collected, and detected by GC-QTOF-MS after liquid-liquid extraction and concentration. The molecular formula of fragments ions was identified by determination of accurate mass numbers, to detect related substances. Results Tiletamine, zolazepam, three metabolites of tiletamine and two metabolites of zolazepam were identified in urine samples from actual cases. Conclusion GC-QTOF-MS provides abundant and accurate information of fragment ions mass numbers, which can be used for qualitative identification of tiletamine, zolazepam and their metabolites in drug facilitated sexual assault.
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Cromatografía Líquida de Alta Presión/métodos , Toxicología Forense/métodos , Cromatografía de Gases y Espectrometría de Masas/métodos , Delitos Sexuales , Espectrometría de Masas en Tándem/métodos , Tiletamina/análisis , Zolazepam/análisis , Humanos , Tiletamina/sangre , Zolazepam/sangreRESUMEN
Multistage coupling of laser-wakefield accelerators is essential to overcome laser energy depletion for high-energy applications such as TeV-level electron-positron colliders. Current staging schemes feed subsequent laser pulses into stages using plasma mirrors while controlling electron beam focusing with plasma lenses. Here a more compact and efficient scheme is proposed to realize the simultaneous coupling of the electron beam and the laser pulse into a second stage. A partly curved channel, integrating a straight acceleration stage with a curved transition segment, is used to guide a fresh laser pulse into a subsequent straight channel, while the electrons continue straight. This scheme benefits from a shorter coupling distance and continuous guiding of the electrons in plasma while suppressing transverse beam dispersion. Particle-in-cell simulations demonstrate that the electron beam from a previous stage can be efficiently injected into a subsequent stage for further acceleration while maintaining high capture efficiency, stability, and beam quality.
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BACKGROUND: Thrombocytopenia is a frequently encountered phenomenon during intra-aortic balloon pumping (IABP), which may limit its prolonged utilization. The aim of the study was to explore the risk factors and clinical implications of IABP-associated thrombocytopenia in patients with acute coronary syndrome (ACS). METHODS: We retrospectively analyzed the data of 222 patients with ACS undergoing invasive treatment strategy supported by IABP. The incidence and risk factors of IABP-associated thrombocytopenia, and the association between thrombocytopenia and relevant clinical endpoints (in-hospital death, bleeding according to the TIMI scale, and thromboembolic events), were analyzed. RESULTS: IABP-associated thrombocytopenia was observed in 54.5% (121/222) of the patients. The incidence of thrombocytopenia was higher and the magnitude of reduction in platelet count was greater in the Arrow balloon group (n = 89) compared with the Datascope balloon group (n = 133; 68.5% vs. 45.1%, p = 0.001; 48.7% vs. 33.2%, p < 0.001; respectively). Independent predictors of thrombocytopenia included older age and Arrow balloon utilization (odds ratio [OR]: 1.054; 95% confidence interval [CI]: 1.028-1.080; p<0.001; OR: 2.468; 95%CI: 1.375-4.431; p = 0.002; respectively). The incidence of in-hospital death was higher in patients who developed thrombocytopenia than those who did not (9.1% vs. 2.0%, p = 0.041), and thrombocytopenia was correlated with in-hospital death (OR: 5.932; 95%CI: 1.221-28.822; p = 0.027). However, the rates of TIMI bleeding and thromboembolic events were similar between the two groups (5.8% vs. 5.0%, p = 1.000; 3.2% vs. 6.0%, p = 0.518; respectively), and thrombocytopenia was not associated with TIMI bleeding or thromboembolic events (OR: 0.940; 95%CI: 0.267-3.307; p = 0.923; OR: 0.541, 95%CI: 0.148-1.974, p = 0.352; respectively). CONCLUSION: IABP-associated thrombocytopenia occurred in 54.5% of patients with ACS undergoing an invasive strategy and it was correlated with increased in-hospital mortality. Older age and use of the Arrow balloon may predict IABP-associated thrombocytopenia.
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Síndrome Coronario Agudo , Contrapulsador Intraaórtico , Intervención Coronaria Percutánea , Trombocitopenia , Síndrome Coronario Agudo/complicaciones , Síndrome Coronario Agudo/terapia , Anciano , Femenino , Heparina , Heparina de Bajo-Peso-Molecular , Humanos , Incidencia , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Trombocitopenia/etiología , Resultado del TratamientoRESUMEN
Objective: To verify the safety and efficacy of IONTRIS particle therapy system (IONTRIS) in clinical implementation. Methods: Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial: 31 males and 4 females with a median age of 69 yrs (range 39-80). Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non-metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation. Results: Twenty-two patients received carbon ion and 13 had proton irradiation. With a median follow-up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression-free survival rate was 93.8% (15/16). Among the 19 patients with prostate cancer, biological-recurrence free survival was 100%. Particle therapy was well tolerated in all 35 patients. Twenty-five patients (71.4%) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow-up. Six (17.1%) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed. Conclusions: IONTRIS is safe and effective for clinical use. However, long term follow-up is needed to observe the late toxicity and long term result.
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Neoplasias de Cabeza y Cuello/radioterapia , Radioterapia de Iones Pesados/métodos , Neoplasias de la Próstata/radioterapia , Terapia de Protones/métodos , Neoplasias Retroperitoneales/radioterapia , Sarcoma/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Neoplasias de Cabeza y Cuello/patología , Radioterapia de Iones Pesados/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/patología , Terapia de Protones/efectos adversos , Neoplasias Retroperitoneales/patología , Sarcoma/patologíaRESUMEN
OBJECTIVE: To explore the influence of SOX10 on the proliferation and invasion of prostate cancer cells. METHODS: SOX10 protein in prostate cancer cell lines PC3, DU145 and LNcap was detected by Western blotting analysis. The expression of SOX10 in prostate cancer cell lines (PC3 and DU145) were knocked down by small interfering RNAs, and the efficiency of SOX10 by small interfering RNAs was confirmed using Western blotting analysis. CCK-8 assays were conducted to assess the influences of SOX10 on the proliferation of PC3 and DU145 cells, and invasion assays were conducted to assess the influences of SOX10 on the invasion of PC3 and DU145 cells. RESULTS: After SOX10 in prostate cancer cells was knocked down by small interfering RNAs, the proliferation of prostate cancer cells PC3 and DU145 was significantly inhibited. Results of CCK-8 assays showed that the absorbance of PC3 and DU145 in SOX10-silenced groups was decreased compared with those in control groups (PC3: 0 d: 0.166±0.01, 0.162±0.012 vs. 0.155 ±0.01, P>0.05; 1 d: 0.210±0.011, 0.211±0.018 vs. 0.252±0.023, P>0.05; 2 d: 0.293±0.017, 0.280±0.028 vs. 0.433±0.030, P<0.01; 3 d: 0.363±0.071, 0.411±0.038 vs. 0.754±0.045, P<0.01; 4 d: 0.592±0.065, 0.670±0.093 vs. 1.456±0.111, P<0.01. DU145: 0 d: 0.168±0.018, 0.164±0.01 vs. 0.153 ±0.012, P>0.05; 1 d: 0.218±0.007, 0.206±0.024 vs. 0.255±0.02, P>0.05; 2 d: 0.297±0.013, 0.291±0.012 vs. 0.444±0.023, P<0.05; 3 d: 0.378±0.058, 0.419±0.026 vs. 0.762±0.039, P<0.01; 4 d: 0.681±0.094, 0.618±0.050 vs. 1.419±0.170, P<0.01). Meanwhile, knocking down SOX10 significantly suppressed the invasion of prostate cancer cells PC3 and DU145. Results of invasion assays showed that the numbers of invaded cells in SOX10-silenced groups were significantly less than those in control groups (PC3: 142±38, 171±17 vs. 304±55; DU145: 96±22, 134±23 vs. 341±34, P<0.05). CONCLUSION: SOX10 might promote prostate cancer progression by accelerating the ability of the proliferation and invasion of prostate cancer cells, and SOX10 might be a potential therapeutic target for prostate cancer.
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Proliferación Celular , Invasividad Neoplásica , Neoplasias de la Próstata , Factores de Transcripción SOXE , Línea Celular Tumoral , Humanos , Masculino , ARN Interferente Pequeño , Factores de Transcripción SOXE/fisiologíaRESUMEN
Objective: To investigate the clinical features and change trend of patients with acute coronary syndrome(ACS) undergoing emergent percutaneous coronary intervention(PCI). Methods: In this retrospective study, we retrieved all medical records of 4 907 ACS patients who underwent emergent PCI in Fuwai hospital from January 1,2010 to December 31,2016. We analyzed the clinical features and change trend in these patients. According to clinical diagnosis, patients were grouped as ST-elevated myocardial infarction(STEMI) group (3 719 cases) and NSTE-ACS group (patients with non-STEMI and unstable angina, 1 188 cases). Results: The ACS patients were aged (59.5±11.8) years old. There were 3 772 males and 1 135 females. The annual number of ACS patients underwent emergent PCI increased from 412 patients in 2010 to 1 067 patients in 2016. The number of NSTE-ACS patients increased from 11.4% (47/412) in 2010 to 26.5% (283/1 067) in 2016. Compared with STEMI group, patients in NSTE-ACS group were significantly older ((61.2±10.9) years old vs. (58.9±12.1) years old,P<0.01).The percent of female patients (30.1% (358/1 188) vs. 20.9% (777/3 719), P < 0.01), history of hypertension (69.1% (821/1 188) vs. 60.4% (2 248/3 719,P <0.01), previous PCI (25.8% (307/1 188) vs. 12.4% (461/3 719), P <0.01), and previous coronary artery bypass grafting (3.0% (36/1 188) vs. 1.0% (37/3 719), P <0.01) were all significantly higher in NSTE-ACS group than in STEMI group. On the other hand, NSTE-ACS patients presented less chronic renal failure (2.9% (35/1 188) vs. 4.3% (173/3 719), P <0.05) and hepatic dysfunction (8.5% (101/1 188) vs. 13.3% (495/3 719), P<0.01) as compared to ACS patients. In coronary angiography, NSTE-ACS patients had a higher prevalence of left-main disease (14.0% (166/1 188) vs. 7.8% (291/3 719), P<0.012 5) and triple vessel disease (47.8% (568/1 188) vs. 43.5% (1 619/3 719), P<0.012 5). There were no differences in prevalence of diabetes mellitus (31.9% (1 187/3 719) vs. 34.8% (414/1 188),P>0.05) and acute renal failure (0.1% (38/3 719) vs. 0.6% (7/1 188),P>0.05) between STEMI group and NSTE-ACS group. Conclusions: This single center retrospective analysis reveals that there is an increasing trend of NSTE-ACS patients from 2010 to 2016. Furthermore, there are more high-risk clinical characteristics in NSTE-ACS patients than in STEMI patients.
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Síndrome Coronario Agudo , Intervención Coronaria Percutánea , Síndrome Coronario Agudo/complicaciones , Síndrome Coronario Agudo/terapia , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio , Estudios Retrospectivos , Infarto del Miocardio con Elevación del STRESUMEN
Self-injection in a laser-plasma wakefield accelerator is usually achieved by increasing the laser intensity until the threshold for injection is exceeded. Alternatively, the velocity of the bubble accelerating structure can be controlled using plasma density ramps, reducing the electron velocity required for injection. We present a model describing self-injection in the short-bunch regime for arbitrary changes in the plasma density. We derive the threshold condition for injection due to a plasma density gradient, which is confirmed using particle-in-cell simulations that demonstrate injection of subfemtosecond bunches. It is shown that the bunch charge, bunch length, and separation of bunches in a bunch train can be controlled by tailoring the plasma density profile.