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Despite advancements in synthetic chemistry, nature remains the primary source of drug discovery, and this never-ending task of finding novel and active drug molecules will continue. Flavonoids have been shown to possess highly significant therapeutic activities such as anti-inflammatory, anti-oxidant, anti-viral, anti-diabetic, anti-cancer, anti-aging, neuroprotective, and cardioprotective, etc., However, it has been found that orally administered flavonoids have a critical absorption disorder and, therefore, have low bioavailability and show fluctuating pharmacokinetic and pharmacodynamic responses. A detailed investigation is required to assess and analyze the variation in the bioavailability of flavonoids due to interactions with the intestinal barrier. This review will emphasize on the bioavailability and the pharmacological applications of flavonoids, key factors affecting their bioavailability, and strategies for enhancing bioavailability, which may lead to deeper understanding of the extent of flavonoids as a treatment and/or prevention for different diseases in clinics.

Subtilisin NAT, a Bacillus subtilisin, is widely applied as a functional food and considered to be one of the most exploitable potential oral thrombolytic agents. Subtilisin QK, another Bacillus subtilisin, is a serine protease fermented by Bacillus subtilis 02 and has a better thrombolytic effect. Therefore, subtilisin QK is typically used for evaluating the safety of Bacillus subtilisins. Here, we conduct several good laboratory practice (GLP)-compliant studies in non-rodent animal, i.e., in Beagle dogs, including acute toxicity, subchronic toxicity, and safety pharmacology studies. No adverse effects were evident in the acute and 28-d subchronic toxicity studies at doses up to 40000 FU/kg and 16000 FU/kg/d, respectively. In evaluating the pharmacological safety of up to 2000FU/kg subtilisin QK, we found no significant differences between the electrocardiograms, blood pressures, and respiration of beagle dogs. These findings suggest the safety of Bacillus subtilisin, providing reliable pharmacological and toxicological data for its development and popularization as a functional food and drug.

Owing to its interconnections and open characteristics, Physical Internet (PI) has the potential to help companies meet the sustainability challenges. In this paper, to investigate the sustainabili...

Background Subtilisin QK is a serine protease in the subtilisin family, and is fermented by Bacillus subtilis QK02. The fibrinolytic activity of subtilisin QK was measured by detecting low molecular weight degradation products using a spectrophotometric method developed by Japan Bio Science Laboratory Co., Ltd. Subtilisin QK powder can maintain its fibrinolytic activity for more than 24 months when it is stored at room temperature and protected from light. Our previous results showed that subtlisin QK directly degraded cross-linked fibrins in the fibrin plate assay and effectively inhibited thrombosis in the mouse thrombus model. The aim of this study was to determine the acute toxicity, potential subchronic toxicity, and safety pharmacology of subtilisin QK in Sprague–Dawley (SD) rats. Methods In the acute toxicity study, a single oral dose of 100,000 FU/kg was administered to 10 female and 10 male SD rats. In the 28-day subchronic toxicity, 60 female and 60 male SD rats were randomly assigned to four experimental groups (daily oral dose of 0, 2500, 7500 and 25,000 FU/kg). In the safety pharmacology study, 20 female and 20 male SD rats were randomly assigned to four experimental groups (single oral dose of 0, 500, 1500 and 5000 FU/kg). Results No death occurred and no adverse effects were observed in the acute toxicity study at a dose of 100,000 FU/kg. In the 28-day subchronic toxicity study, several hematological and blood biochemical parameters showed increases or decreases; however, due to the lack of a dose–response relationship, these differences were considered unrelated to treatment. In the safety pharmacology study, no adverse effects were observed on the central nervous of SD rats post-administration up to a dose of 5000 FU/kg subtilisin QK. Conclusion The results showed that oral consumption of subtilisin QK is of low toxicological concern. No adverse effects were observed at doses of 2500, 7500, and 25,000 FU/kg in the 28-day subchronic toxicity, and the no-observed-adverse-effect level (NOAEL) of subtilisin QK was 25,000 FU/kg.

Hereditary hemochromatosis and β-thalassemia can both result in the inappropriately low production of the hormone hepcidin, which leads to an increase in intestinal absorption and excessive iron deposition in the parenchymal cells. To the best of our knowledge, there have been no reports on the coexistence of the two disorders in China. We herein report a case in a Chinese who presented with late-onset hepatic cirrhosis with hereditary hemochromatosis and β-thalassemia. We analyzed the pedigree of the two disorders and the iron status in his family members. Our case supports that a heterozygous H63D mutation can interact with β-thalassemia, leading to late-onset hemochromatosis.

In the past decade, urban last-mile logistics (ULML) has attracted increasing attention with the growth of e-commerce. Under this background, express cabinet has been gradually advocated to improve...

Background To investigate the comparative effectiveness of stereotactic body radiotherapy (SBRT) and sublobar resection (SLR) in patients with stage I non-small cell lung cancer (NSCLC) considered to be high-risk lobectomy patients. Methods From January 2012 to December 2015, patients who underwent SBRT or SLR for clinical stage I NSCLC were examined retrospectively. Propensity score matching (PSM) was performed to reduce selection bias in SBRT and SLR patients. Results Data from 86 SBRT and 79 SLR patients was collected. Median follow-up periods of the SBRT and SLR groups were 32 and 37 months, respectively. Patients treated with SBRT exhibited significantly higher age, higher likelihood of being male, larger tumor diameter, lower forced expiratory volume in 1 second (FEV1), and poorer performance status compared with SLR patients. There were no significant differences between SBRT and SLR patients for 3-year overall survival (OS) (80.3% and 82.3%, P=0.405), cause-specific survival (CSS) (81.3% and 83.4%, P=0.383), and local control (LC) (89.7% and 86.0%, P=0.501). Forty-nine patients were identified from each group after performing PSM. After patients were matched for age, gender, performance status, tumor characteristics and pulmonary function, no significant differences were observed in 3-year OS (85.4% and 73.3%, P=0.649), CSS (87.2% and 74.9%, P=0.637) and LC (95.6% and 82.1%, P=0.055). Prevalence of significant adverse events (grade 3 or worse) was 0% and 10.2% in the matched SBRT and SLR groups (P=0.056), respectively. Conclusions Disease control and survival in the SBRT patients was equivalent to that seen in SLR patients with stage I NSCLC considered high-risk lobectomy candidates. SBRT could therefore be an alternative option to SLR in treating patients with a high operative risk.

Objective: The purpose of this study was to explore if the dimensions of the ischiofemoral space on MRI vary with changes in external femoral rotation in Ischifemoral Impingement patients relative to healthy control; if so, to determine the optimal diagnostic cutoff values of these dimensions in Ischifemoral Impingement. Methods: The study included 43 clinically confirmed Ischifemoral Impingement patients and 50 healthy volunteers. All subjects underwent hip MRI examinations with their hips externally rotated at 0°, 30° and 60°. The IFS and QFS were measured respectively at each angle. The measurements were compared between the IFI group and the control group to determine the optimal diagnostic cutoff values for diagnosing IFI by using IFS and QFS measurements. Results: In the IFI group, the spaces were smaller than those of the control group at all rotation angles (P < 0.05 for each). When external rotation angles were increased, the IFS and QFS tended to decrease. QFSs were smaller in the case group than the control group at each rotation angle. The receiver operating characteristic areas under the curves of IFS and QFS in a neutral position of 0° were highest. Conclusion: Both of the IFS and QFS spaces of IFI patients were found to be smaller than those of control group, regardless of the external hip rotation angles. A neutral position of 0° was deemed the best position for diagnosing IFI. The diagnostic cutoff values of IFS and QFS were 2.44cm and 1.34cm in the neutral position, respectively.

Background Previous research has shown that stereotactic body radiation therapy (SBRT) can achieve a high level of tumor control in patients with early-stage non-small cell lung cancer (NSCLC). However, to date, such studies have mainly focused on peripheral early-stage patients. This study aimed to assess the clinical outcomes and toxicity of patients with central lung cancer treated with SBRT in our institution. Methods A total of 31 consecutive central early-stage NSCLC patients who were treated with SBRT using the biologically effective dose (BED; α/β =10) 100-119 Gy in 4-10 fractions between April, 2013, and August, 2016, were reviewed. The RTOG 0813 trial standard was used to define whether the NSCLC was centrally located. All patients received four-dimensional computed tomography (4D CT) simulation. Intensity modulated radiation therapy (IMRT) and three-dimensional conformal radiation therapy (3D CRT) techniques were used in treatment planning. The dose to the planning target volume (PTV) was prescribed to the 95% isodose line. Mainly dosimetric parameters, clinical outcomes, and toxicity were analyzed. Results The 31 patients enrolled in the study had a median follow-up time of 47.7 months, and the median tumor diameter was 2.2 cm (range, 1.3-5.0 cm). A total of 15 patients (48.4%) developed disease recurrence. The incidences of local, regional, and distant disease recurrence at 3 years were 11.7%, 9.7%, and 30.7%, respectively; at 5 years, they were 21.5%, 15.0%, and 35.0%, respectively. The 3- and 5-year progression-free survival (PFS) rates were 55.1% and 40.5%, respectively; the corresponding overall survival (OS) rates were 85.3% and 68.4%, respectively. Toxicities of grade 3 or higher were observed in 6.5% of the patients. None of the patients experienced grade 4 or 5 acute adverse events; however, 2 patients possibly died of treatment-related late toxicity. Conclusions SBRT with a BED 100 Gy in 4-10 fractions is effective and acceptable for treating patients with central early-stage NSCLC. Further studies are warranted.

Ameliorated therapy based on the tumor microenvironment is becoming increasingly popular, yet only a few methods have achieved wide recognition. Herein, targeting multifunctional hydrophilic nanomicelles, AgBiS2@DSPE-PEG2000-FA (ABS-FA), were obtained and employed for tumor treatment. In a cascade amplification mode, ABS-FA exhibited favorable properties of actively enhancing computed tomography/infrared (CT/IR) imaging and gently relieving ambient oxygen concentration by cooperative photothermal and sonodynamic therapy. Compared with traditional Bi2S3 nanoparticles, the CT imaging capability of the probe was augmented (43.21%), and the photothermal conversion efficiency was increased (33.1%). Furthermore, remarkable ultrasonic dynamic features of ABS-FA were observed, with increased generation of reactive oxygen species (24.3%) being obtained compared to Ce6, a commonly used sonosensitizer. Furthermore, ABS-FA exhibited obvious inhibitory effects on HeLa cell migration at 6 μg/mL, which to some extent, demonstrated its suppressive effect on tumor growth. A lower dose, laser and ultrasonic power, and shorter processing time endowed ABS-FA with excellent photothermal and sonodynamic effects. By mild cascade mode, the hypoxic condition of the tumor site was largely improved, and a suitable oxygen-rich environment was provided, thereby endowing ABS-FA with a superior synergistically enhanced treatment effect compared with the single-mode approach, which ultimately realized the purpose of "one injection, multiple treatment". Moreover, our data showed that ABS-FA was given with a biological safety profile while harnessing in vivo. Taken together, as a synergistically enhanced medical diagnosis and treatment method, the one-for-all nanoplatform will pave a new avenue for further clinical applications.

The osteoporosis was common complication of ankylosing spondylitis (AS), but it was frequently unrecognized in the initial stage of the disease. This study was to compare areal bone mineral density (BMD) of hip joints in early AS patients with that in healthy controls, to explore the progress of bone loss in cortex and spongiosa in early AS. Quantitative computed tomography (QCT) of hip was performed in 60 AS patients (modified New York criteria for AS, with grade 2 sacroiliitis in computed tomography) and 57 healthy controls. The QCT measurements of AS patients were compared with the measurements of healthy controls. The AS patients had lower areal BMD in cortical bone and total bone of proximal femur in early AS patients (P

Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a life-threatening hyperinflammatory syndrome triggered by EBV infection. It often becomes relapsed or refractory (r/r), given that etoposide-based regimens cannot effectively clear the virus. r/r EBV-HLH is invariably lethal in adults without allogeneic hematopoietic stem cell transplantation. Here, we performed a retrospective analysis of 7 r/r EBV-HLH patients who were treated with nivolumab on a compassionate-use basis at West China Hospital. All 7 patients tolerated the treatment and 6 responded to it. Five of them achieved and remained in clinical complete remission with a median follow-up of 16 months (range, 11.4-18.9 months). Importantly, both plasma and cellular EBV-DNAs were completely eradicated in 4 patients. Single-cell RNA-sequencing analysis showed that HLH syndrome was associated with hyperactive monocytes/macrophages and ineffective CD8 T cells with a defective activation program. Nivolumab treatment expanded programmed death protein-1–positive T cells and restored the expression of HLH-associated degranulation and costimulatory genes in CD8 T cells. Our data suggest that nivolumab, as a monotherapy, provides a potential cure for r/r EBV-HLH, most likely by restoring a defective anti-EBV response.

Acute myeloid leukemia (AML) bears heterogeneous cells that can consequently offset killing by single-CAR-based therapy, which results in disease relapse. Leukemic stem cells (LSCs) associated with CD123 expression comprise a rare population that also plays an important role in disease progression and relapse. Here, we report on the robust anti-tumor activity of a compound CAR (cCAR) T-cell possessing discrete scFv domains targeting two different AML antigens, CD123, and CD33, simultaneously. We determined that the resulting cCAR T-cells possessed consistent, potent, and directed cytotoxicity against each target antigen population. Using four leukemia mouse models, we found superior in vivo survival after cCAR treatment. We also designed an alemtuzumab safety-switch that allowed for rapid cCAR therapy termination in vivo. These findings indicate that targeting both CD123 and CD33 on AML cells may be an effective strategy for eliminating both AML bulk disease and LSCs, and potentially prevent relapse due to antigen escape or LSC persistence.

// Huda Salman 1, 2 , Xiao Shuai 2, 3, * , Anh Thu Nguyen-Lefebvre 1, * , Banabihari Giri 1 , Mingqiang Ren 1 , Michael Rauchman 4 , Lynn Robbins 4 , Wei Hou 2 , Hasan Korkaya 1 and Yupo Ma 2 1 Georgia Regent University Cancer Center, Augusta, GA, USA 2 Present address: Stony Brook University Cancer Center, Stony Brook, NY, USA 3 Department of Hematology, West China hospital of Sichuan University, Chengdu, P.R. China 4 Department of Nephrology, Saint Louis University, St Louis, MO, USA * These authors contributed equally to this work Correspondence to: Huda Salman, email: huda.salman@stonybrookmedicine.edu Keywords: SALL1; AML Received: August 18, 2017 Accepted: October 25, 2017 Published: December 15, 2017 ABSTRACT Similar signaling pathways could operate in both normal hematopoietic stem and progenitor cells (HSPCs) and leukemia stem cells (LSCs). Thus, targeting LSCs signaling without substantial toxicities to normal HSPCs remains challenging. SALL1, is a member of the transcriptional network that regulates stem cell pluripotency, and lacks significant expression in most adult tissues, including normal bone marrow (NBM). We examined the expression and functional characterization of SALL1 in NBM and in acute myeloid leukemia (AML) using in vitro and in vivo assays. We showed that SALL1 is expressed preferentially in LSCs- enriched CD34+CD38- cell subpopulation but not in NBM. SALL1 inhibition resulted in decreased cellular proliferation and in inferior AML engraftment in NSG mice and it was also associated with upregulation of PTEN and downregulation of m-TOR, β-catenin, and NF- қB expression. These findings suggest that SALL1 inhibition interrupts leukemogenesis. Further studies to validate SALL1 as a potential biomarker for minimal residual disease (MRD) and to determine SALL1’s role in prognostication are ongoing. Additionally, pre-clinical evaluation of SALL1 as a therapeutic target in AML is warranted.

Miniaturized percutaneous nephrolithotomy (MPCNL), including minipercutaneous nephrolithotomy (PCNL), ultramini-PCNL, and micro-PCNL, have been developed recently. The aim of this meta-analysis was to compare the safety and efficacy of different tract sizes of MPCNL with retrograde intrarenal surgery (RIRS) in the management of kidney stones.We searched PubMed, Embase, and Web of Science to identify case-control trials and randomized controlled trials, which evaluated MPCNL vs RIRS before February 2017. Two reviewers independently evaluated the methodologic quality of the included studies, and the disagreements were solved by discussion. Meta-analysis was performed with Review Manager version 5.3 software.Fourteen publications involving 1279 patients were included. Mini-PCNL provided a significantly higher stone-free rate (SFR; odds ratio [OR] OR 1.66; p = 0.005), especially for lower pole renal stones (OR 2.65; p = 0.003), but brought longer hospital stay (weighted mean difference [WMD] 1.23; p = 0.0001) and larger hemoglobin drop (WMD 0.77; p 0.00001). There were no statistically significant differences between mini-PCNL and RIRS in the complications (OR 0.77; p = 0.23) and operative time (WMD: -6.52; p = 0.42). For ultramini-PCNL and micro-PCNL, the safety and efficacy were similar to RIRS.Mini-PCNL offers a significantly higher SFR than RIRS, for lower pole renal stones, the advantage of mini-PCNL is more obvious. However, RIRS is associated with shorter hospital stay and less hemoglobin drop. For ultramini-PCNL and micro-PCNL, tract size is smaller than mini-PCNL, and the SFR is similar to RIRS. In terms of the evidence at present, we recommend mini-PCNL for patients focusing more on the high SFR.

Current clinical outcomes using chimeric-antigen receptors (CARs) against multiple myeloma show promise in the eradication of bulk disease. However, these anti-BCMA (CD269) CARs observe relapse as a common phenomenon after treatment due to the reemergence of either antigen-positive or -negative cells. Hence, the development of improvements in CAR design to target antigen loss and increase effector cell persistency represents a critical need. Here, we report on the anti-tumor activity of a CAR T-cell possessing two complete and independent CAR receptors against the multiple myeloma antigens BCMA and CS1. We determined that the resulting compound CAR (cCAR) T-cell possesses consistent, potent and directed cytotoxicity against each target antigen population. Using multiple mouse models of myeloma and mixed cell populations, we are further able to show superior in vivo survival by directed cytotoxicity against multiple populations compared to a single-expressing CAR T-cell. These findings indicate that compound targeting of BCMA and CS1 on myeloma cells can potentially be an effective strategy for augmenting the response against myeloma bulk disease and for initiation of broader coverage CAR therapy.

Vessels operating in shallow waters require careful observation of the finite-depth effect. In present study, a Rankine source method that includes the shallow water effect and double body steady flow effect is developed in frequency domain. In order to verify present numerical methods, two experiments were carried out respectively to measure the wave loads and free motions for ship advancing with forward speed in head regular waves. Numerical results are systematically compared with experiments and other solutions using the double body basis flow approach, the Neumann-Kelvin approach with simplified m -terms, and linearized free surface boundary conditions with double-body m -terms. Furthermore, the influence of water depths on added mass and damping coefficients, wave excitation forces, motions and unsteady wave patterns are deeply investigated. It is found that finite-depth effect is important and unsteady wave pattern in shallow water is dependent on both of the Brard number τ and depth Froude number F h .

Objectives To explore the role of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) and CCRT plus adjuvant chemotherapy (AC) in locoregionally advanced nasopharyngeal carcinoma (LANPC). Materials and methods The propensity score-matched (PSM) method was adopted to balance variables. We identified independent prognostic factors using Cox regression analysis and compared outcomes between two chemotherapy treatment combinations for patients in different subgroups. Results A total of 550 patients were selected by one-to-two PSM. Survival outcomes for the matched data set indicated that the IC + CCRT group achieved higher 5-year overall survival (OS; 89.3% vs 85.3%, P = 0.119), failure-free survival (FFS; 80.2% vs 79.0%, P = 0.722) and distant metastasis-free survival (DMFS; 87.4% vs 84.4%, P = 0.322) compared with CCRT + AC, although this was statistically non-significant. Subgroup analysis revealed that IC + CCRT was associated with significantly improved OS (Hazard ratio [HR] = 2.68, 95% Confidence interval [CI] = 1.16–6.22, P = 0.017), FFS (HR = 1.94, 95% CI = 1.06–3.57, P = 0.029) and locoregional relapse-free survival (LRRFS; HR = 2.63, 95% CI = 1.04–6.68, P = 0.034) in T3 disease. Moreover, this combination of treatment could significantly prolong OS (HR = 3.72, 95% CI = 1.41–9.80, P = 0.004) in N2 disease. However, the superiority of CCRT + AC was only observed in LRRFS (HR = 0.18, 95% CI 0.04–0.79, P = 0.010) for the T4 subgroup. Conclusion IC + CCRT should be strongly considered by patients with LANPC, especially those with T3 or N2 disease.

e21052 Background: For patients with unresectable stage III disease, combined modality therapy (chemoradiation) is superior to radiation alone, and concurrent chemoradiotherapy (CCRT) is superior to sequential chemoradiotherapy (SCRT). The current standard of care for unresectable stage III disease is CCRT. Consequently, CCRT is commonly given to patients with minimal or no comorbidities, a good general condition, and who are relatively young. SCRT may be a valuable alternative for patients who are not eligible for CCRT. However, the role of salvage radiotherapy (SRT) after chemotherapy for patients with unresectable stage III disease without CCRT or SCRT is currently unknown. Methods: Patients with unresectable stage III disease receiving chemoradiotherapy were enrolled. All patients were treated with CCRT, SCRT or SRT. Overall survival (OS) was estimated by Kaplan-Meier curves. Results: From May 2014 to September 2018, 216 patients were enrolled, including 65 (30.1%) who received CCRT, 80 (37.0%) who received SCRT, and 71 (32.9%) who received SRT. No significant difference in gender, age, performance status, TNM stage, or EGFR gene status among the three groups. The median OS for the entire cohort was 22.1 (range: 18.4–25.8) months. The median OS in CCRT, SCRT, and SRT group were 29.7, 21.3, and 19.1 months, respectively (P = 0.011). The difference was statistically significant between CCRT group and SCRT or SRT group but was not between SCRT and SRT group. The 1-year survival rate in CCRT, SCRT, and SRT group were 89.2%, 75.0%, and 75.2%, respectively. However, the 3-year survival rate in CCRT, SCRT, and SRT group were 42.7%, 32.7%, and 9.6%, respectively. However, CCRT also has a higher rate of Grade 3 or 4 acute esophagitis and pneumonitis . Conclusions: The current study demonstrated compared with CCRT and SCRT, SRT had reduced patient survival survival time significantly.

A graphene quantum dot (GQD) is a novel carbon nanomaterial with the advantages of low cost and no pollution. It has attracted serious attention in the biomedical fields because of its stabilities and tunable fluorescence wavelength. In this manuscript, an N-doped graphene quantum dot (N-GQD) was synthesized by a hydrothermal method using citric acid as the carbon source and urea as the nitrogen source. X-ray diffraction, Raman spectroscopy, transmission electron microscopy, UV-vis absorption spectrum, and fluorescence spectrum were used to characterize the N-GQD. The results showed that the N-GQD had a uniform size of about 5 nm. The two fluorescence emission peaks, one in the visible light region showed a 49.75% quantum yield, while another in the near infrared region was 2.49%. The photothermal conversion efficiency was 62.53%, higher than any kind of carbon nanomaterial in existence today. MTT and a long-term cytotoxicity experiment confirmed that the N-GQD had low cytotoxicity. The probe also had the ability of photoacoustic response at the same time. After coupling with folic acid, it presented imaging and photothermal therapy on the cells, which has great application prospects in the early diagnosis and treatment of tumors.

This study was to validate the animal model for the research in the stage of recovery and sequela of ischemic stroke. For its recognized many advantages and widespread applications, middle cerebral artery occlusion / reperfusion (MCAO/R) in Male Sprague-Dawley rats was chosen to be the foundation model. Then the weight of rats (260–330 g), the thread bolt type (2636/2838/3040/3043), the time of brain infarct (2/3 h) were tested to choose the larger infarct volume, higher Longa's score and model success rate through Longa's score and TTC staining. Finally, optimum condition of model was used in long period observing from 1 to 90 days after MCAO/R via five assessment of sensorimotor functions and TTC staining. The results showed that the optimal rat model of cerebral infarction in the stage of recovery and sequela of ischemic stroke maybe the model rats which were 300 g weight and MCAO with 3040 line-lock for 3 h before reperfusion. In these conditions, the Longa's score was 2.1 ± 0.2, and infarct volume was 23.0 ± 2.4%. The sensorimotor functional test of bilateral asymmetry had significant difference from 1 to 90 days, the test of grid-walking had significant difference from 1 to 60 days, while other tests had significant difference only at 1 day after MCAO/R. In conclusion, 3040–300 g-3 h was the most appropriate condition, and the appropriate index of sensorimotor functions were bilateral asymmetry and grid-walking test.

The dead zone and voltage drop of inverter power switches make the currents in asynchronous motor drive system contain a large amount of harmonic. This aberration of currents waveform influences the efficiency of motor drive system. Aim at this problem, this paper proposes a harmonic injection method to eliminate the currents harmonic component when the motor is running, which improves currents waveform of motor and boosts efficiency of motor drive system. The effectiveness and real-time performance of this algorithm is verified via the simulation and the contrast experiment. Through the result of simulation, five times harmonic content decreased from 9% to 2%, the total harmonic distortion of voltage (THD) decreased from 6% to 2%, and efficiencyis increased from 98.99% to 99.95%.

A new type powertrain system architecture for city electric bus was introduced, which combines the function of Extended-Range Electric Vehicle (E-REV) and Plug-in Hybrid Electric Vehicle (P-HEV). Five driving modes were designed and its dynamics were analyzed. Numerical method on dynamics was proposed. The dynamic performance parameter of five drive modes were calculated and analyzed. The results indicate that the dynamic performance reaches the limit value at full drive mode and meet the requirement of city bus.

In view of the difference in design, construction and the usage of the old and the new bridges, there are always stress defects in seamline because of the concrete creep and shrinkage, temperature effect and prestress loss, which seriously affect the service and driving safety. The current ways in foreign and domestic, such as plant steel and semi-rigid connection method, are passive processing based on structure, can’t ensure the long-term performance. According to the three direction stress existing in the seamline, this paper decomposes the material contribution and structure influence, putting forward respectively using material and structure to overcome the adverse situation, using material to remove partial long-term effect, and through the sensitivity analysis of related parameters, to make the structure bearing the rest adverse effect, ensuring the long-term performance of seamline. The relevant conclusion can provide reference for the design and construction of the concrete bridge seamline.

A novel low voltage ride through (LVRT) control strategy is designed by using sliding mode control (SMC), based on the analysis of dynamic mathematical models of the doubly fed induction generators. This method chooses two sliding surfaces according to the requirement of LVRT. It designs control strategies by combining function Lyapunov and exponential reaching law. The results of common vector control and this strategy are compared by simulation experiment of grid voltage depth dropping, which shows that the novel control strategy is better than traditional vector control strategy and is beneficial for the system quick recovery after faults£®

Wind speed forecasting is an effective method to improve power stability of wind farm. Grey system theory have certain advantages in the study of poor information and uncertainty problems, it is suitable for the system with limited computing power and data storage capacity, such as wind turbine control system. In order to further improve the prediction accuracy of grey model, we combined GM (1, 1) model and BP neural network prediction model in this paper, and improved the combined model by background value optimizing and introducing genetic algorithm. Through analyzing the simulation results and comparing the forecasting results with the actual wind speed, it is clear that the improved combined prediction model is superior to pure grey forecasting model and it meets the needs of the wind power control.

This paper studied the principles of thermal gas mass flow meter. According to the car engine EGR cooler working principle, we found out a kind of heat dissipation gas mass flow meter to measure the mass flow quantity of the gas in the EGR cooler test and analysis system which is a newly applied invention patent. We analyzed various parameters of the gas mass flow meter suitable to the system. Meanwhile, in order to verify reliability of the thermal gas mass flow meter in the system, we adopted CFD method to simulate the EGR cooler by using empirical parameters, and collected several related sensor parameters of the EGR cooler in the condition that the inlet temperature was constantly at 368K while the coolant had 4 kinds of degrees. Combining heat empirical formula, we got the EGR cooler outlet temperature and the overall heat transfer coefficient. After comparing the calculated values of the gas path total EGR cooler outlet temperature and heat transfer coefficients with the experimental values, we found that the outlet temperature values of experiment were smaller than the calculated values by averagely 1.17%, while the average experimental values of the overall heat transfer coefficient were 3.1% larger than the calculated values. Thus, this type of mass flow meter has good stability in the newly applied Chinese patent EGR cooler performance test and analysis system.

Tarenflurbil (R-flurbiprofen) was acknowledged as a promising candidate in Alzheimer's disease (AD) therapy. However, the Phase III study of tarenflurbil was extremely restricted by its poor delivery efficiency to the brain. To tackle this problem, the novel carriers for tarenflurbil, racemic flurbiprofen (FLU) derivatives (FLU-D1 and FLU-D2) modified by N,N-dimethylethanolamine-related structures were synthesized and characterized. These derivatives showed good safety level in vitro and they possessed much higher cellular uptake efficiency in brain endothelial cells than FLU did. More importantly, the uptake experiments suggested that they were internalized via active transport mechanisms. Biodistribution studies in rats also illustrated a remarkably enhanced accumulation of these derivatives in the brain. FLU-D2, the ester linkage form of these derivatives, achieved a higher brain-targeting efficiency. Its Cmax and AUC0-t were enhanced by 12.09-fold and 4.61-fold, respectively compared with those of FLU. Additionally, it could be hydrolyzed by esterase in the brain to release the parent FLU, which might facilitate its therapeutic effect. These in vitro and in vivo results highlighted the improvement of the brain-targeted delivery of FLU by making use of N,N-dimethylethanolamine ligand, with which an active transport mechanism was involved.

CXC chemokine receptor 4 (CXCR4) expression on acute myeloid leukemia (AML) cells correlated with stromal cell derived factor-1α (SDF-1α) and retained hematopoietic progenitors and leukemia cells within the bone marrow microenvironment. Here, we examined CXCR4 expression in 134 de novo AML and 21 controls by flow cytometry, evaluated the relationship between CXCR4 expression and clinical characteristics, and elucidated the prognostic significance of CXCR4 expression in AML prospectively. We found that the CXCR4 expression was significantly higher in AML patients than controls (P = .000). One hundred thirty four cases of de novo AML patients were divided into 2 groups according to the median of CXCR4 relative fluorescence intensity (RFI). CXCR4 high group (RFI >4.23) had markedly shorter overall survival (OS) and disease-free survival (DFS) than CXCR4 low group (RFI ≤4.23) in 106 AML patients who received chemotherapy (P = .002; .026, respectively). Furthermore, in the 87 non-M3 patients who received induction therapy, there was a significant decrease for OS but not for DFS in the CXCR4 high group (P = .047 and .178, respectively). Moreover, high levels of CXCR4 expression independently increased the risk of relapse in both all AML and non-M3 patients who achieved complete remission (CR) after chemotherapy (odds ratio = 1.090, P = .010; odds ratio = 1.068, P = .048, respectively). Collectively, our data suggest that CXCR4 overexpression was an independent prognostic factor for disease relapse and poorer OS in both all AML and non-M3 patients. CXCR4 expression levels can be determined at disease presentation by the flow rapidly and easily. As such, CXCR4 could be used as a potential therapeutic target in AML patients with poor prognosis.

This article presents a kind of high sensitive magnetic transducer which is based on the phase characteristics of giant magnet-impedance (GMI) effect. Then the development process of this new kind of magnetic transducer is discussed with the ideal condition of the GMI sensor elements (the frequency and the amplitude of the excitation current). Compared with the amplitude characteristics of GMI effect, the transducer can make a 10 to 100 times lower frequency. At the ideal condition, the sensor has a sensitivity of 1.6°/Oe, and we can conclude that the sensor has a potential to detect the weak magnetic.

In order to study the influence of heel on bubble layer shape and stability, based on Fluent and Mixture model, a numerical model was established to calculate bubble layer shape at the plate bottom at different main flow velocity, air flow rate and heel degree. The influence on bubble layer shape and skin friction reduction rate caused by heel was investigated. The results show that: bubble layer at the plate bottom spreads with the inflow transversely and longitudinally. When there is heel degree, bubble layer drifts to the smaller draft side. As heel degree increases, the drift of bubble layer becomes larger and the skin friction reduction rate decreases greatly. The local skin friction even increases greatly at the plate bottom apart from the air injection board. Both local void ratio and local friction reduction rate decreases in the longitudinal direction along the plate. Local void ratio is bigger than local friction reduction rate and the difference increases in the longitudinal direction along the plate.

Permanent-Magnet-Biased Saturation Based Fault Current Limiter (PMFCL) is a preferable solution to suppress the fault current, and may find early applications in large capacity power systems due to prominent advantages. Firstly, the topologies and the operating principles of the PMFCLs are elucidated in this paper. Then a new concept namely effective magnetic flux density is proposed in order to describe the overall impacts of the magnetic field on the current limiting capacity of the PMFCLs. Lastly, theoretical analysis and mathematical simulation on the dynamic characteristics of different modes of PMFCLs are carried out comparatively. All the results present invaluable fundamentals for further study on the operating mechanism of different modes of PMFCLs as well as optimization of the fault current limiting topology design.

Summary What is known and objective Rituximab, an anti-CD20 monoclonal antibody, is widely used with good response for the treatment of B-cell lymphoma and various refractory autoimmune diseases. Although rituximab is effective, rare but serious pulmonary adverse reactions have been reported. We report on a case of rituximab-induced life-threatening interstitial lung disease in a patient with diffuse large B-cell lymphoma (DLBCL), and describe the patient's serum cytokine profile during anti-TNF-α treatment. Case summary: A 71-year-old woman diagnosed with DLBCL was treated with three cycles of rituximab-containing chemotherapy. She developed a fatal respiratory failure, which was eventually diagnosed as rituximab-induced interstitial lung disease (R-ILD). The R-ILD in this patient did not respond to intensive steroid treatment, or to enternacept, an anti-TNF therapy. During therapy, we observed that the serum level of IL-6 was much higher at the beginning of treatment than was usual for other DLBCL patients. Levels of IL-6 and TNF-α also increased during the course of the clinical exacerbation. We undertook a literature search and reviewed similar cases of R-ILD. What is new and conclusion Although rituximab is generally effective and safe, caution is required for high-risk patients, as in our case, and as reported in several other cases in the literature. Cytokine analysis may help in identifying patients at high risk of R-ILD. Better intensive therapeutic approaches other than steroids are required even during the early stages of the complication.

A device for measuring high-TC superconducting transition temperature in a small cryocooler is described which allows a samples temperature to fall steadily from room temperature to 45K. This cryocooler not only meets the high-TC superconductors measurement requirements, but also yields accurate measurement results under ambient conditions. In this device, two measurement methods for measuring high-TC superconducting transition temperature are applied: the electric transport and the AC susceptibility. The former adopts a four-wire method to eliminate the contact resistance between the leads and the sample. During the measurement process the current reversal method for datum processing is applied to eliminate the thermoelectric voltages; this ensures the repeatability error less than 0.4K in the measurement of the superconducting transition temperature. The AC susceptibility method adopts a lock-in amplifier to provide an AC voltage signal for the primary coil, and then lock-in amplifier is used to measure the electrical signals of the secondary coil according to the AC magnetic susceptibility values. The advantage of this device is that by merely changing the position of the sample in the vacuum chamber, the R-T curve and the χ-T curve of a superconducting sample in the same temperature range can be automatically recorded, which provides reliable data for high-TC superconductor transition curve measurement.

With the development of new energy vehicle, the current air conditioner technology has been unable to meet the requirement of future automobile. In this paper, the characteristics of traditional automobile air conditioner is summarized. And several new air conditioners, adapting to the new energy vehicles are putted forward. Compared with traditional air conditioner, these new air conditioners are more possible to be used in the future vehicles.

Recent years, automobile air-conditioner control system is particularly important as the automobile air-conditioner is becoming an important indicator to measure the comfort of a car. This paper introduces the hardware and software design of the system based on STC12C5A60S2 microcontroller.The hardware design part includes the circuits design of motor and fan, and the software design part describes the way to realize the modes conversion function. Experiments show that the automobile air-conditioner system can reach high control accuracy and it's practical.

This paper presented a method for recording and reconstructing high-quality digital color holographic images. Digital holography with three different wavelength lasers and a monochrome CCD has been demonstrated. With the phase-shifting of the reference beam, in-line holograms for three wavelengths are recorded successively for derivation of the complex amplitude at each wavelength. The three monochromatic interferograms are reconstructed and combined into full-color images in the computer. Laser power variation for wavelength can be compensated for the reconstruction process.

The average time required for cancers to progress through stages can be reflected in the average age of the patients diagnosed at each stage of disease. To estimate the time it takes for non-small-cell lung cancer (NSCLC) to progress through different tumor, node and metastasis (TNM) stages and sizes, we compared the mean adjusted age of 45904 NSCLC patients with different stages and tumor sizes from Surveillance, Epidemiology and End Results (SEER) cancer registry database and our institute. Multiple-linear-regression models for age were generated adjusting for various factors. Caucasian, African-American and Asian patients with stage IA cancers were on average 0.8, 1.0 and 1.38 adjusted years younger, respectively, than those with stage IIIB cancers (p

When the bridges broaden with seamless technology, there are differences between the existing bridge and the new bridge in design, construction and service. Because of concrete creep and shrinkage, temperature effect and prestress loss, there are stress defects in the seam, which will affect the service and safety. The current methods for the seam in foreign and domestic, such as plant steel and semi-rigid connection method are passive measures based on structure exiting state, which cannot ensure the long-term performance of the seam.

An experimental study was carried out on a prototype of a scroll expander used as the air-powered vehicle engine. The speed characteristic was tested based on the test system at the constant suction temperature and pressure. The results show that the air mass consumption rate and the output power both increase with the rotating speed. The maximum air mass consumption rate is 800kg/h and the maximum power achieves 8.112 kW. The effective efficiency increases with the rotating speed but the increment decreases. The maximum efficiency is only 0.26 due to the low manufacturing and assembly accuracy of the expander.

This paper will put forward a device installed into the fuel system, which can use the sliding electric arc to electrolyze the natural gas to make hydrogen and then blend them in the fuel pipe for final combustion. This device can help to make a new type of HCNG engine fuel system, which electrolyses the single fuel (natural gas) partly to make appropriate-rate hydrogen for combustion. And in this paper, this new fuel system will be described in detail. The picture of sliding electric arc is shown in the end of this paper.

The research is conducted on emulsified fuel applied to engine YC6J190 without any modification of the engine. In this experiment, the contrast of the fuel consumption and the emissions is studied with having water or not. From the results, it can be concluded that the emulsified fuel can reduce the NOx and smoke emissions greatly at the same time, but the fuel consumption is different in different conditions. The emulsified fuel with 20% water is most suitable for this type of engine regarding fuel consumption and emissions. Then dynamic characteristics is tested using the emulsified fuel with 20% water to find that the decline in power and torque output is not apparent. At the end, we conclude that emulsion containing 20% of water would replace diesel as for this type of engine.

Type B lactic acidosis (LA) is a distinct form of metabolic acidosis characterized by low blood pH (≤ 7.35) accompanied by accumulation of lactate (blood concentration ≥ 5 mmol/L) (Luft et al. in Am J Clin Pathol 80:484-489, 1983). There are two types of LA that are caused by different mechanisms. Type A is more common, and is caused by the lack of oxygen (tissue hypoxia or hypoperfusion). In this case, impaired cellular respiration leads to lower pH level and at the same time the cells are forced to metabolize glucose anaerobically, which leads to increased production of lactate. The other type, Type B, is relatively rare, and is occasionally found in patients with hematological malignancies, such as leukemia or lymphoma. The molecular mechanism of Type B LA is not fully understood. Here, we report a case of precursor B cell acute lymphoblastic leukemia who initially shows manifestations of Type B LA and bilateral renal enlargement.

As wind turbines (WTs) become larger in size, they are experiencing increasing structural loads on their flexible components. This may shorten the working life of WTs or even cause damage to them. This work proposes a nonlinear individual pitch control (IPC) strategy to mitigate blade fatigue load for WTs operating in the above-rated wind speed region. The controller consists of a blade vibration damper and a pitch angle lead compensator for each blade. The damper is used to damp the vibration of the blades, which is designed by nonlinear dynamic inversion (NDI) method to deal with the non-affine nonlinearity of the WT model. The lead compensator is used to compensate the delay between pitch angle command and actual angle caused by the pitch actuator. The simulation results with the aero-elastic model of FAST show that the nonlinear controller has a better system performance, compared with several other IPC controllers. Besides, the proposed approach is able to work well in large wind speed range, and is easy to implement for industrial applications.

Objective. Hemophagocytic lymphohistiocytosis (HLH), also known as Hemophagocytic Syndrome (HPS), is an increasingly recognized clinical syndrome that is characterized by extreme immune activation. HLH was first described as an inherited immune disorder in pediatrics, but it may also arise in adults as the result of persistent antigen stimulation due to infections, autoimmune disorders or malignancies. Early recognition of HLH and appropriate treatment are critically important. For the pediatric patients, the Histiocyte Society Study Group for HLH has developed the HLH-94 and HLH-2004 treatment protocols, but there is no such guideline or consensus for adult HLH. Although there were increasing amount of clinical studies in adult HLH, the majority of them just described the etiologies and clinical profiles, and failed to analyze the treatment effects on outcomes. Therefore, there is an urgent need for more clinical data focusing on treatment in adult HLH patients, in order to clarify optimal therapeutic regimens. Our study retrospectively analyzed the causes, treatment strategies, and relevant outcomes in 104 adult HLH patients in our institution, and with the goal of identifying more appropriate therapeutic strategies for adult HLH patients. Methods. After the approval of our protocol by local institutional Ethics Committee, the medical records of 104 consecutive patients with adult onset HLH in West China Hospital from June 2008 to February 2016 were reviewed. The diagnosis was re-confirmed according to HLH-04 criteria, and demographic data, clinical profiles, treatments and outcomes were collected and analyzed. The latest follow-up visit occurred on 1st July 2016. The different therapeutic effects on prognosis were discussed based on the endpoints which were defined as short-term (30 days) and long-term (last follow-up date) survival rates. Statistical analysis was performed on SAS 9.4 software, and was involved in Log-rank test in univariate analysis and Cox proportional hazard regression model in multivariate analysis. All p values were two-sided and p Results. All of 104 consecutive patients with adult HLH were enrolled in this study. The male/female ratio was 1.6:1 with the median age of 35 (range 16-77). In etiological classification, 75 cases were lymphoma-associated HLH, 13 cases were infection-associated HLH, 2 cases were with autoimmune disorders, and for the remaining 14 cases, the underlying diseases could not be identified. In treatment analysis, corticosteroids were used in 91 cases (87.5%), the median initiation time was 0 day (range 0-26 days) after HLH diagnosis, the median four-week accumulating dosage was 236.57mg dexamethasone. Etoposide was employed in 55 cases (52.9%), the median initiation time was 3.5 days (range 0-62 days), the median four-week accumulating dosage was 590.00mg. Cyclosporine A (CSA) was used in 42 cases (40.4%), the median initiation time was 2 days (range 0-51 days), the median four-week accumulating dosage was 7100.00mg. The median survival time for all patients was 46 days (1-2529 days). On the 30th day after admission, 27 patients (26.0%) had died, and 77 patients (74.0%) had survived. At the last follow-up visit, 74 patients (71.2%) had died, 17 patients (16.2%) were still alive, and 13 patients had been lost to follow-up. Statistical analysis indicated that patients in etoposide-treated group was associated with superior short-term survival rate, compared with non-etoposide-treated group (p=0.0471), but there was no difference in long-term survival rate between the two groups. CSA-treated group was associated with inferior long-term survival rate (p=0.0214), compared with non-CSA-treated group. In patients with lymphoma-associated HLH, those who received antineoplastic chemotherapy had a higher long-term survival rate than those who did not receive it (HAZARD=0.07, p Conclusion. The major underlying diseases of adult onset HLH are malignant lymphomas. Etoposide might only improve the short-term survival, but fail to change the long-term survival. Immunosuppressor CSA seems to be associated with negative effects on long-term survival rate. For patients with lymphoma-associated HLH, antineoplastic chemotherapy might improve the long-term outcome. More clinical prospective studies should be initiated for adult acquired HLH. Disclosures No relevant conflicts of interest to declare.

After analyzing advantages and disadvantages of original methods that analyze students' grade and evaluate teaching quality with average grade, this paper proposed a new method that use the transfer matrix obtained by markov chain to analyze students' grade and evaluate teaching quality. Markov chain use scores transition matrix of students to illustrate the changes in student achievement, eliminating the subjective factor, which can provide better, more objective assessment of teaching quality.

According to the specific requirements of national standards on transient emission measurement system, an emission measurement system with VMAS is constructed. The components and theory of VMAS are introduced. The system’s repeatability is discussed based on test results. Then the possibility and importance are discussed about adoption the VMAS testing method for emission inspection of in-use petrol vehicles in China.

A novel Hybrid Clustering Algorithm (HCA) that incorporates the K-means into the canonical Immune Programming Algorithm (IPA) is proposed after analyzing the advantages and disadvantages of the classical k-means clustering algorithm in the paper. The theory analysis and experimental results show the algorithm not only avoids the local optima and is robust to initialization, but also increases the convergent speed, meanwhile evidently restrains the degenerating phenomenon during the evolutionary process.