Objective： This study was designed to determine the safety, pharmacokinetics and biologic effects of a humanmouse chimeric anti-CD20 monoclonal antibody （SCT400） in Chinese padents with CD20-positive B-cell non- Ho...Objective： This study was designed to determine the safety, pharmacokinetics and biologic effects of a humanmouse chimeric anti-CD20 monoclonal antibody （SCT400） in Chinese padents with CD20-positive B-cell non- Hodgkin＇s lymphoma （CD20 B-cell NHL）. SCT400 has an identical amino acid sequence as rituximab, with the exception of one amino acid in the CH1 domain of the heavy chain, which is common in Asians. Methods： Fifteen patients with CD20＋ B-cell NHL received dose-escalating SCT400 infusions （250 mg/m2： n=3; 375 mg/m2： n=9; 500 mg/m2： n=3） once weekly for 4 consecutive weeks with a 24-week follow-up period. The data of all patients were collected for pharmacoklnetics and pharmacodynamics analyses. Results： No dose-limiting toxicities were observed. Most drug-related adverse events were grade 1 or 2. Two patients had grade 3 or 4 ncutropenia. Under premedication, the drug-related infusion reaction was mild. A rapid, profound and durable depletion of circulating B cells was observed in all dose groups without significant effects on T cell count, natural killer （NK） cell count or immunoglobulin levels. No patient developed anti- SCT400 antibodies during the course of the study. SCT400 serum half-life （Tin）, maximum concentration （Cmax and area under the curve （AUC） generally increased between the first and fourth infusions （P〈0.05）. At the 375 mg/m2 dose, the T1/2 was 122.5±46.7 h vs. 197.0,75.0 11, respectively, and the Cmax was 200.6±20.2 pg/mL vs. 339.1±71.0 ng/mL, respectively. From 250 mg/m2 to 500 mg/m2, the Cmax and AUC increased significantly in a dose-dependent manner （P〈0.05）. Patients with a high tumor burden had markedly lower serum SCT400 concenmations compared with those without or with a low tumor burden. Of the 9 assessable patients, 1 achieved complete response and 2 achieved partial responses. Conclusions; SCT400 is well-tolerated and has encouraging preliminary efficacy in Chinese patients with CD20＋ B-cell NHL.展开更多
Objective： The recommended dose of prophylactic pegylated recombinant human granulocyte-colony stimulating factor（PEG rhG-CSF） is 100 μg/kg once per cycle for patients receiving intense-dose chemotherapy.However, ...Objective： The recommended dose of prophylactic pegylated recombinant human granulocyte-colony stimulating factor（PEG rhG-CSF） is 100 μg/kg once per cycle for patients receiving intense-dose chemotherapy.However, few data are available on the proper dose for patients receiving less-intense chemotherapy. The aim of this phase I study is to explore the proper dose and administration schedule of PEG rhG-CSF for patients receiving standard-dose chemotherapy.Methods：Eligible patients received 3-cycle chemotherapy every 3 weeks.No PEG rhG-CSF was given in the first cycle.Patients experienced grade 3 or 4 neutropenia would then enter the cycle 2 and 3.In cycle 2,patients received a single subcutaneous injection of prophylactic PEG rhG-CSF on d 3,and received half-dose subcutaneous injection in cycle 3 on d 3 and d 5,respectively.Escalating doses（30,60,100 and 200μg/kg）of PEG rhG-CSF were investigated.Results：A total of 26 patients were enrolled and received chemotherapy,in which 24 and 18 patients entered cycle 2 and cycle 3 treatment,respectively.In cycle 2,the incidence of grade 3 or 4 neutropenia for patients receiving single-dose PEG rhG-CSF of 30,60,100 and 200 μg/kg was 66.67%,33.33%,22.22% and 0,respectively,with a median duration less than 1（0–2）d.No grade 3 or higher neutropenia was noted in cycle 3 in all dose cohorts.Conclusions：The pharmacokinetic and pharmacodynamic profiles of PEG rhG-CSF used in cancer patients were similar to those reported,as well as the safety.Double half dose administration model showed better efficacy result than a single dose model in terms of grade 3 neutropenia and above.The single dose of 60 μg/kg,100 μg/kg and double half dose of 30 μg/kg were recommended to the phase Ⅱ study,hoping to find a preferable method for neutropenia treatment.展开更多
The miscibility and phase behavior of the blends of polyoxymethylene (POM)/Novolak were investigated by the cloud point method, which showed that the POM/Novolak blends exhibited a lower critical solution temperature....The miscibility and phase behavior of the blends of polyoxymethylene (POM)/Novolak were investigated by the cloud point method, which showed that the POM/Novolak blends exhibited a lower critical solution temperature. The melting point of POM decreased when diluted with Novolak. From the melting temperature depression of POM, a negative interaction parameter (x) between POM and Novolak was obtained. The IR spectrum revealed that the miscibility between POM and Novolak was caused by the specific interaction between the OH groups of Novolak and the ether oxygen atoms of POM. The morphology of the blends investigated by polarized light microscopy showed that the size of spherulites of POM was sharply decreased by its mixing with Novolak. This suggests that Novolak be used as a compatibilizer for POM.展开更多
In-situ HVEM observation on phase transition of the YBa_2Cu_3O_(7-x) superconducting compound in pro- cess of heating was carried out,and high temperature X-ray diffraction analysis in air and X-ray diffraction phase ...In-situ HVEM observation on phase transition of the YBa_2Cu_3O_(7-x) superconducting compound in pro- cess of heating was carried out,and high temperature X-ray diffraction analysis in air and X-ray diffraction phase analysis for the sample treated in vacuum condition were made.The results showed that the temperature of phase transition is related to oxygen content in the sample and in general,is 100℃ to 120℃ lower in vacu- um condition than in air.At 320℃ to 350℃ twin bands begin to disappear,and some Cu_2O are formed on the surface of the sample and transit from orthorhombic YBa_2Cu_3O_(7-x) to arthorhombic Y_2BaCuO_5 compound. This transition was completed at about 500℃.Above 900℃,this compound consists of the Y_2BaCuO_5, BaCuO_2,Y_2O_3 and some other minor compounds.No phase transition was observed during cooling the sample.展开更多
Objective： The mitomycin C and cisplatin combination was investigated in patients with advanced breast cancer who had been exposed to anthracyclines, vinorelbine and taxanes. Methods： Three-weekly regimen consisted ...Objective： The mitomycin C and cisplatin combination was investigated in patients with advanced breast cancer who had been exposed to anthracyclines, vinorelbine and taxanes. Methods： Three-weekly regimen consisted of mitomycin, 6 mg/m^2 administered intravenously on day 1, and cisplatin, 25 mg/m^2 intravenously on day 1-3. Results： Thirty-eight patients aged 25-75 years （median, 46 years） were treated with an overall response rate of 31.6%. The median time to progression （TTP） was 4.0 months. Median TTP for 12 patients with a complete or partial response was 9.0 months, while stable disease and progression of disease 4.0 months, P=0.002. Grade 3/4 side effects of neutropenia, thrombocytopenia and nausea/vomiting were documented in 4 （10.5%）, 4 （10.5%） and 3 （7.9%） patients, respectively. The median overall survival was 13＊ months. Conclusion： Mitomydn C/cisplatin doublet showed antitumor activity for anthracydine-, vinorelbine- and taxane-resistant breast cancer comparable to other regimens. This well-tolerated regimen provides an affordable option for patients in China.展开更多
The elastocalorie effect of PbTiO3 thin films with 180° domain structure is studied using the phase field method. The influence of external stress σ33, misfit strain μm and domain wall energy on the adiabatic t...The elastocalorie effect of PbTiO3 thin films with 180° domain structure is studied using the phase field method. The influence of external stress σ33, misfit strain μm and domain wall energy on the adiabatic temperature change （ △ Tσ） at room temperature are carried out. The calculation results indicate that ｜△Tσ｜ increases as ｜σ33｜ or ｜μm｜ increases. The largest △ Tσ wlue of--7.81（ is obtained at σ33 = 2 GPa and Um =-0.02. Furthermore, the domain switching behaviors under different gradient coeffcients are different, and finally affect the elastocaloric effect in PTO thin films. These results could provide a guide to choose the substrate and the preparation process in experiments.展开更多
INTRODUCTIONThe studies on the quantitative distribution of the conventional elements and their phases in the sediments of the Changjiang Estuary are of great importance to the understanding of the chemical processes ...INTRODUCTIONThe studies on the quantitative distribution of the conventional elements and their phases in the sediments of the Changjiang Estuary are of great importance to the understanding of the chemical processes of ion exchange, absorption, desorption and flocculation in the estuary.展开更多
Purpose: Investigation of safety, tolerability, pharmacokinetics, and anti-tumor activity of the Lewis Y-specific, fully humanized monoclonal antibody (mAb) IGN311 in patients with Lewis Y positive tumors in a Phase I...Purpose: Investigation of safety, tolerability, pharmacokinetics, and anti-tumor activity of the Lewis Y-specific, fully humanized monoclonal antibody (mAb) IGN311 in patients with Lewis Y positive tumors in a Phase I clinical trial. Experimental Design: Twelve patients (pts) were enrolled in an open-label, uncontrolled, dose escalating Phase I study. Three pts received 50 mg, three pts 100 mg and six pts 200 mg IGN311 by i.v. infusion on days 1 and 15. Blood samples were taken immediately before infusion, and 0.5, 4, 8, 24 hours post infusion, as well as on days 3, 5 and 8 after the first and second infusion, respectively, and day 29. A final visit was scheduled for day 43. Results: No drug related adverse events were observed in the 50 mg and 100 mg dose groups. Three out of six patients in the 200 mg dose group showed drug related adverse reactions with nausea, vomiting and hypotension in one patient (NCI CTC grade 3) being the dose limiting toxicities. t1/2 of IGN311 was ~20 days after second infusion of IGN311. Sera of patients receiving IGN311 were capable of lysing Lewis Y positive tumor cells in vitro by both, complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Circulating tumor cells found in the peripheral blood in two out of twelve pts prior to treatment were reduced after treatment to below the quantification limit of the detection method. None of the patients showed an increase in the number of disseminated tumor cells during treatment period. Conclusions: The good safety and PK profile, the biological activity regarding CDC and ADCC mediated tumor cell lysis, and the elimination of circulating tumor cells warrant further clinical investigation of IGN311.展开更多
A reliable,selective and sensitive liquid chromatography tandem mass spectrometry method was developed and validated for the quantification of lamotrigine in human plasma using lamotrigine13C3,d3 as an internal standa...A reliable,selective and sensitive liquid chromatography tandem mass spectrometry method was developed and validated for the quantification of lamotrigine in human plasma using lamotrigine13C3,d3 as an internal standard.Analyte and internal standard were extracted from human plasma by solid-phase extraction and detected in positive ion mode by tandem mass spectrometry with electrospray ionization（ESI） interface.Chromatographic separation was performed on a Chromolith s SpeedROD;RP-18e column（50-4.6 mm i.d.） using acetonitrile：570.1 mM ammonium formate solution（90：10,v/v） as the mobile phase at a flow rate of 0.500 mL/min.The calibration curves were linear over the range of 5.02-1226.47 ng/mL with the lower limit of quantitation validated at 5.02 ng/mL.The analytes were found stable in human plasma through three freeze（-20℃）-thaw（ice-cold water bath） cycles and under storage on bench-top in ice-cold water bath for at least 6.8 h,and also in the mobile phase at 10℃ for at least 57h.The method has shown good reproducibility,as the intra-and inter-day precisions were within 3.0%,while the accuracies were within 76.0% of nominal values.The validated LC-MS/MS method was applied for the evaluation of pharmacokinetic and bioequivalence parameters of lamotrigine after an oral administration of 50mg lamotrigine tablet to thirty-two healthy adult male volunteers.展开更多
Phase evolution and magnetic properties of (Nd_o.95La_0.05)9.5-11Febal.M_2B10.5. where M=Cr, Ti, Nb, V, Mo, Zr, Hf, Ta, Mn or W, melt spun ribbons have been investigated. Almost all the alloy ribbons. except for(Nd_0....Phase evolution and magnetic properties of (Nd_o.95La_0.05)9.5-11Febal.M_2B10.5. where M=Cr, Ti, Nb, V, Mo, Zr, Hf, Ta, Mn or W, melt spun ribbons have been investigated. Almost all the alloy ribbons. except for(Nd_0.95La_0.05)_9.5Fe_78M_2B_10.5(M=Mo and Mn),consist merely two magnetic phases, namely α-Fe and R_2Fe_14B, which display a better combination of _iH_c and magnetic energy product. Remanence (Br) and coercivity (i_H_c) values in the range of 8.0 to 9.1 kG and 9.5 to 18.9 kOe. respectively, can be achieved. Among compositions studied, the Ti and W-substitutions were found to be most effective in increasing the Br and i_H_c, respectively. For a fixed refractory metal substitution, namely, M=C_r, Ti or Nb, an increase in the total rare earth concentration resulted in nanocomposites of small grain sizes and a high volume fraction of the R_2Fe_14B phase, leading to an increase in the magnetic properties.展开更多
A rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry（UPLC-MS/MS） method is described for determination of letrozole in human plasma.Following solid phase extraction（SPE） of letroz...A rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry（UPLC-MS/MS） method is described for determination of letrozole in human plasma.Following solid phase extraction（SPE） of letrozole and letrozole-d4 on Orochem DVB-LP cartridges,chromatography was performed on Acquity UPLC BEH C_（18）（50 mm × 2.1 mm.1.7 μm） column using methanol-0.1%formic acid in water（85：15,v/v） as the mobile phase.Detection was carried out on a triple quadrupole mass spectrometer with an electrospray source,operated under positive ionization mode.Quantitation of letrozole and letrozole-d4 was done using multiple reaction monitoring（MRM） following the transitions at m/z286.2→217.0 and m/z 290.2→221.0,respectively.The calibration plots were linear through the concentration range of 0.10-100 ng/mL（r^2 ≥ 0.9990） using 100 μL human plasma.The extraction recovery of letrozole ranged from 94.3%to 96.2%and the intra-batch and inter-batch precision was ≤ 5.2%.The method was successfully applied to a bioequivalence study of letrozole after oral administration of2.5 mg tablet formulation to 16 healthy postmenopausal Indian women.The assay reproducibility was also established through incurred sample reanalysis（ISR） of 74 subject samples.展开更多
The present paper contains the effects of the ammonium ion, counter ion, solvent and anion being transferred on the solid-liquid phase transfer equilibrium constant of quaternary ammonium salts. The most striking diff...The present paper contains the effects of the ammonium ion, counter ion, solvent and anion being transferred on the solid-liquid phase transfer equilibrium constant of quaternary ammonium salts. The most striking difference between solid-liquid and liquid-liquid phase transfer equilibriums is that the length of alkyl chain shows a large effect on the latter but little on the former This means that the chain length affects only the hydrophobicity, rather than the lipophilicity.Keywords Quaternary ammonium salt, Phase transfer catalysis, Equilibrium constant, Hydrophobicity, Lipophilicity展开更多
The lytropic liquid crystals in dodecanic acid diethanolamine (DAD) /n-butanol (C4OH) /octane (n-C8H18) /deuteron (D2O) system were studied to determine the phase regions and were investigated by 2H-NMR spectroscopy,o...The lytropic liquid crystals in dodecanic acid diethanolamine (DAD) /n-butanol (C4OH) /octane (n-C8H18) /deuteron (D2O) system were studied to determine the phase regions and were investigated by 2H-NMR spectroscopy,optical polarizing microscope and small-angle X-ray diffraction (SAXD) methods.The results indicate that the lamellar,hexagonal and cubic liquid crystals all exist in the above system.Keeping the weight ratio of DAD and C4OH constant,the microphase Structure,2H quadruple splitting and the interlayer spacing are all changed with the addition of deuteron.展开更多
Recently biospecific affinity chromatography has been widely used for the separation and purification of various enzymes and nucleic acids. In this paper, a series of synthetic reactions of solid-liquid phase were car...Recently biospecific affinity chromatography has been widely used for the separation and purification of various enzymes and nucleic acids. In this paper, a series of synthetic reactions of solid-liquid phase were carried out on silica surface, using a macroporous(30 mu m), microspherical silica (8 mu m) as the matrix and gamma-aminopropyltriethoxysilane as the activating agent, the nicotinamide adenine dinucleotide(NAD) was bonded through its amino groups to the carboxylic groups of linked phospholipid which was bonded covalently on aminated support. The bonded stationary phase has high thermal stability, and could be used to separate of nucleotides with good resolution.展开更多
A one-step sintering process of bauxite raw material from direct mining was completed, and the kinetics of this process was analyzed thoroughly. The results show that the sintering kinetics of bauxite raw material exh...A one-step sintering process of bauxite raw material from direct mining was completed, and the kinetics of this process was analyzed thoroughly. The results show that the sintering kinetics of bauxite raw material exhibits the liquid-phase sintering behavior. A small portion of impurities existed in the raw material act as a liquid phase. After X-ray diffraction analyses, scanning electron microscopy observations, and kinetics calculations, sintering temperature and heating duration were determined as the two major factors contributing to the sintering process and densification of bauxite ore. An elevated heating temperature and longer duration favor the densification process. The major obstacle for the densification of bauxite material is attributed to the formation of the enclosed blowhole during liquid-phase sintering.展开更多
Background:Several programmed cell death ligand 1(PD-L1)/programmed cell death protein 1(PD-1)antibodies have been approved for cancer treatmentworldwide.Their pharmacokinetic and pharmacodynamic characteristics have ...Background:Several programmed cell death ligand 1(PD-L1)/programmed cell death protein 1(PD-1)antibodies have been approved for cancer treatmentworldwide.Their pharmacokinetic and pharmacodynamic characteristics have been reported mainly in western countries,but related data in Chinese patients are limited.This study was conducted to investigate the safety,efficacy,pharmacokinetics,and pharmacodynamics of an anti-PD-1 antibody,toripalimab,in Chinese patients.Methods:A single-center phase I study was conducted in Sun Yat-sen University Cancer Center.Eligible patients were adults with histologically confirmed,treatment-refractory,advanced,solitary malignant tumors.Toripalimab was intravenously infused every 2 weeks in dose-escalating cohorts at 0.3mg/kg,1 mg/kg,3 mg/kg,10 mg/kg,and 240 mg.The study followed standard 3+3 design.Results:Between 15th March 2016 and 27th September 2016,25 patients were enrolled,of whom 3(12.0%),7(28.0%),6(24.0%),6(24.0%),3(12.0%)received 0.3 mg/kg,1 mg/kg,3 mg/kg,10 mg/kg,and 240 mg toripalimab,respectively.After a median follow-up time of 5.0 months(range:1.5-19.8 months),we observed that the commonest treatment-related adverse events(TRAEs)were fatigue(64.0%)and rash(24.0%).No grade 3 or higher TRAEs were observed.No dose-limiting toxicity,treatment-related serious adverse events(SAEs),or treatment-related death occurred.Objective response ratewas 12.5%.The half-life of toripalimabwas 150-222 h after a single dose infusion.Most patients,including those from the 0.3 mg/kg group,maintained complete PD-1 receptor occupancy(>80%)on activated T cells since receiving the first dose of toripalimab.Conclusions:Toripalimab is a promising anti-PD-1 antibody,which was well tolerated and demonstrated anti-tumor activity in treatment-refractory advanced solitary malignant tumors.Further exploration in various tumors and combination therapies is warranted.展开更多
An orthogonal test was used to optimize the reaction conditions of roasting zinc oxide ore using（NH_4）_2SO_4. The optimized reaction conditions are defined as an（NH_4）_2SO_4/zinc molar ratio of 1.4：1, a roasting ...An orthogonal test was used to optimize the reaction conditions of roasting zinc oxide ore using（NH_4）_2SO_4. The optimized reaction conditions are defined as an（NH_4）_2SO_4/zinc molar ratio of 1.4：1, a roasting temperature of 440°C, and a thermostatic time of 60 min. The molar ratio of（NH_4）_2SO_4/zinc is the most predominant factor and the roasting temperature is the second significant factor that governs the zinc extraction. Thermogravimetric-differential thermal analysis was used for（NH_4）_2SO_4 and zinc mixed in a molar ratio of 1.4：1 at the heating rates of 5, 10, 15, and 20 K·min-1. Two strong endothermic peaks indicate that the complex chemical reactions occur at approximately 290°C and 400°C. XRD analysis was employed to examine the transformations of mineral phases during roasting process. Kinetic parameters, including reaction apparent activation energy, reaction order, and frequency factor, were calculated by the Doyle-Ozawa and Kissinger methods. Corresponding to the two endothermic peaks, the kinetic equations were obtained.展开更多
A new theoretical method with generality is proposed to study the statistical properties of the speckle phase. The general expression of the standard deviation of the speckle phase about the first-order statistics is ...A new theoretical method with generality is proposed to study the statistical properties of the speckle phase. The general expression of the standard deviation of the speckle phase about the first-order statistics is derived according to the relation between the phase and the complex speckle amplitude. The statistical properties of the speckle phase have been studied in the diffraction fields with this new theoretical method.展开更多
An improved high performance liquid chromatography-tandem mass spectrometry（LC-MS/MS） method has been developed for sensitive and rapid determination of albendazole（ABZ） and its active metabolite,albendazole sulfo...An improved high performance liquid chromatography-tandem mass spectrometry（LC-MS/MS） method has been developed for sensitive and rapid determination of albendazole（ABZ） and its active metabolite,albendazole sulfoxide（ABZSO）,in the positive ionization mode.The method utilized solid phase extraction（SPE） for sample preparation of the analytes and their deuterated internal standards（ISs） from100 μL human plasma.The chromatography was carried out on Hypurity C_（18） column using acetonitrile-2.0 mM ammonium acetate,pH 5.0（80：20,v/v） as the mobile phase.The assay exhibited a linear response over the concentration range of 0.200-50.0 ng/mL for ABZ and 3.00-600 ng/mL for ABZSO.The recoveries of the analytes and ISs ranged from 86.03%-89.66%and 89.85%-98.94%,respectively.Matrix effect,expressed as IS-normalized matrix factors,ranged from 0.985 to 1.042 for the both analytes.The method was successfully applied for two separate studies in healthy subjects using single dose of 400 mg conventional tablets and 400 mg chewable ABZ tablets,respectively.展开更多
Ultrasound imaging is the most widely used noninvasive medical imaging modality. Its latest elite concept is Superharmonic Imaging which is the most talked-about future of medical diagnostic ultrasound. In this paper,...Ultrasound imaging is the most widely used noninvasive medical imaging modality. Its latest elite concept is Superharmonic Imaging which is the most talked-about future of medical diagnostic ultrasound. In this paper, the computational and analytical study for superharmonic field generation from phased array transducer of 16 × 16 elements is presented. For this, the model preferred, includes the calculation for diffraction effect in frequency domain and nonlinear effect in time domain. The attenuation is included along with the diffraction in frequency domain as well. The comparative analysis of superharmonic field is also carried out with simulated fundamental and second harmonic fields by the same model. Similarly, the comparison with the results from the literature is also reported.展开更多
基金supported in part by Chinese National Major Project for New Drug Innovation (2008ZX09312-020,2009ZX09503-014,2012ZX09303012 and 2013ZX09402301)National Key Technology Support Program (2014BAI09B12)+1 种基金Beijing Municipal Science and Technology Commission Major Project for New Drug Innovation (Z111102071011001)Beijing Municipal Science and Technology Commission Project for Beijing Key Laboratory (Z121102009212055)
文摘Objective： This study was designed to determine the safety, pharmacokinetics and biologic effects of a humanmouse chimeric anti-CD20 monoclonal antibody （SCT400） in Chinese padents with CD20-positive B-cell non- Hodgkin＇s lymphoma （CD20 B-cell NHL）. SCT400 has an identical amino acid sequence as rituximab, with the exception of one amino acid in the CH1 domain of the heavy chain, which is common in Asians. Methods： Fifteen patients with CD20＋ B-cell NHL received dose-escalating SCT400 infusions （250 mg/m2： n=3; 375 mg/m2： n=9; 500 mg/m2： n=3） once weekly for 4 consecutive weeks with a 24-week follow-up period. The data of all patients were collected for pharmacoklnetics and pharmacodynamics analyses. Results： No dose-limiting toxicities were observed. Most drug-related adverse events were grade 1 or 2. Two patients had grade 3 or 4 ncutropenia. Under premedication, the drug-related infusion reaction was mild. A rapid, profound and durable depletion of circulating B cells was observed in all dose groups without significant effects on T cell count, natural killer （NK） cell count or immunoglobulin levels. No patient developed anti- SCT400 antibodies during the course of the study. SCT400 serum half-life （Tin）, maximum concentration （Cmax and area under the curve （AUC） generally increased between the first and fourth infusions （P〈0.05）. At the 375 mg/m2 dose, the T1/2 was 122.5±46.7 h vs. 197.0,75.0 11, respectively, and the Cmax was 200.6±20.2 pg/mL vs. 339.1±71.0 ng/mL, respectively. From 250 mg/m2 to 500 mg/m2, the Cmax and AUC increased significantly in a dose-dependent manner （P〈0.05）. Patients with a high tumor burden had markedly lower serum SCT400 concenmations compared with those without or with a low tumor burden. Of the 9 assessable patients, 1 achieved complete response and 2 achieved partial responses. Conclusions; SCT400 is well-tolerated and has encouraging preliminary efficacy in Chinese patients with CD20＋ B-cell NHL.
基金supported by Hangzhou Jiuyuan Gene Engineering Co., Ltdpartly funded by the Chinese National Science and Technology Major Project on Key New Drug Creation (2012ZX09303-012)Beijing Municipal Science & Technology Commission Major Project for New Drug Innovation (Z111102071011001), China
文摘Objective： The recommended dose of prophylactic pegylated recombinant human granulocyte-colony stimulating factor（PEG rhG-CSF） is 100 μg/kg once per cycle for patients receiving intense-dose chemotherapy.However, few data are available on the proper dose for patients receiving less-intense chemotherapy. The aim of this phase I study is to explore the proper dose and administration schedule of PEG rhG-CSF for patients receiving standard-dose chemotherapy.Methods：Eligible patients received 3-cycle chemotherapy every 3 weeks.No PEG rhG-CSF was given in the first cycle.Patients experienced grade 3 or 4 neutropenia would then enter the cycle 2 and 3.In cycle 2,patients received a single subcutaneous injection of prophylactic PEG rhG-CSF on d 3,and received half-dose subcutaneous injection in cycle 3 on d 3 and d 5,respectively.Escalating doses（30,60,100 and 200μg/kg）of PEG rhG-CSF were investigated.Results：A total of 26 patients were enrolled and received chemotherapy,in which 24 and 18 patients entered cycle 2 and cycle 3 treatment,respectively.In cycle 2,the incidence of grade 3 or 4 neutropenia for patients receiving single-dose PEG rhG-CSF of 30,60,100 and 200 μg/kg was 66.67%,33.33%,22.22% and 0,respectively,with a median duration less than 1（0–2）d.No grade 3 or higher neutropenia was noted in cycle 3 in all dose cohorts.Conclusions：The pharmacokinetic and pharmacodynamic profiles of PEG rhG-CSF used in cancer patients were similar to those reported,as well as the safety.Double half dose administration model showed better efficacy result than a single dose model in terms of grade 3 neutropenia and above.The single dose of 60 μg/kg,100 μg/kg and double half dose of 30 μg/kg were recommended to the phase Ⅱ study,hoping to find a preferable method for neutropenia treatment.
文摘The miscibility and phase behavior of the blends of polyoxymethylene (POM)/Novolak were investigated by the cloud point method, which showed that the POM/Novolak blends exhibited a lower critical solution temperature. The melting point of POM decreased when diluted with Novolak. From the melting temperature depression of POM, a negative interaction parameter (x) between POM and Novolak was obtained. The IR spectrum revealed that the miscibility between POM and Novolak was caused by the specific interaction between the OH groups of Novolak and the ether oxygen atoms of POM. The morphology of the blends investigated by polarized light microscopy showed that the size of spherulites of POM was sharply decreased by its mixing with Novolak. This suggests that Novolak be used as a compatibilizer for POM.
文摘In-situ HVEM observation on phase transition of the YBa_2Cu_3O_(7-x) superconducting compound in pro- cess of heating was carried out,and high temperature X-ray diffraction analysis in air and X-ray diffraction phase analysis for the sample treated in vacuum condition were made.The results showed that the temperature of phase transition is related to oxygen content in the sample and in general,is 100℃ to 120℃ lower in vacu- um condition than in air.At 320℃ to 350℃ twin bands begin to disappear,and some Cu_2O are formed on the surface of the sample and transit from orthorhombic YBa_2Cu_3O_(7-x) to arthorhombic Y_2BaCuO_5 compound. This transition was completed at about 500℃.Above 900℃,this compound consists of the Y_2BaCuO_5, BaCuO_2,Y_2O_3 and some other minor compounds.No phase transition was observed during cooling the sample.
文摘Objective： The mitomycin C and cisplatin combination was investigated in patients with advanced breast cancer who had been exposed to anthracyclines, vinorelbine and taxanes. Methods： Three-weekly regimen consisted of mitomycin, 6 mg/m^2 administered intravenously on day 1, and cisplatin, 25 mg/m^2 intravenously on day 1-3. Results： Thirty-eight patients aged 25-75 years （median, 46 years） were treated with an overall response rate of 31.6%. The median time to progression （TTP） was 4.0 months. Median TTP for 12 patients with a complete or partial response was 9.0 months, while stable disease and progression of disease 4.0 months, P=0.002. Grade 3/4 side effects of neutropenia, thrombocytopenia and nausea/vomiting were documented in 4 （10.5%）, 4 （10.5%） and 3 （7.9%） patients, respectively. The median overall survival was 13＊ months. Conclusion： Mitomydn C/cisplatin doublet showed antitumor activity for anthracydine-, vinorelbine- and taxane-resistant breast cancer comparable to other regimens. This well-tolerated regimen provides an affordable option for patients in China.
基金Supported by the National Natural Science Foundation of China under Grant Nos 11502078 and 11402222the General Project of Hunan Provincial Department of Education under Grant No 15C0535the Start-up Foundation of High-talent Research Project of Hunan University of Science and Technology under Grant No E51517
文摘The elastocalorie effect of PbTiO3 thin films with 180° domain structure is studied using the phase field method. The influence of external stress σ33, misfit strain μm and domain wall energy on the adiabatic temperature change （ △ Tσ） at room temperature are carried out. The calculation results indicate that ｜△Tσ｜ increases as ｜σ33｜ or ｜μm｜ increases. The largest △ Tσ wlue of--7.81（ is obtained at σ33 = 2 GPa and Um =-0.02. Furthermore, the domain switching behaviors under different gradient coeffcients are different, and finally affect the elastocaloric effect in PTO thin films. These results could provide a guide to choose the substrate and the preparation process in experiments.
基金The project was supported by the National Natural Science Foundation of China.
文摘INTRODUCTIONThe studies on the quantitative distribution of the conventional elements and their phases in the sediments of the Changjiang Estuary are of great importance to the understanding of the chemical processes of ion exchange, absorption, desorption and flocculation in the estuary.
文摘Purpose: Investigation of safety, tolerability, pharmacokinetics, and anti-tumor activity of the Lewis Y-specific, fully humanized monoclonal antibody (mAb) IGN311 in patients with Lewis Y positive tumors in a Phase I clinical trial. Experimental Design: Twelve patients (pts) were enrolled in an open-label, uncontrolled, dose escalating Phase I study. Three pts received 50 mg, three pts 100 mg and six pts 200 mg IGN311 by i.v. infusion on days 1 and 15. Blood samples were taken immediately before infusion, and 0.5, 4, 8, 24 hours post infusion, as well as on days 3, 5 and 8 after the first and second infusion, respectively, and day 29. A final visit was scheduled for day 43. Results: No drug related adverse events were observed in the 50 mg and 100 mg dose groups. Three out of six patients in the 200 mg dose group showed drug related adverse reactions with nausea, vomiting and hypotension in one patient (NCI CTC grade 3) being the dose limiting toxicities. t1/2 of IGN311 was ~20 days after second infusion of IGN311. Sera of patients receiving IGN311 were capable of lysing Lewis Y positive tumor cells in vitro by both, complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Circulating tumor cells found in the peripheral blood in two out of twelve pts prior to treatment were reduced after treatment to below the quantification limit of the detection method. None of the patients showed an increase in the number of disseminated tumor cells during treatment period. Conclusions: The good safety and PK profile, the biological activity regarding CDC and ADCC mediated tumor cell lysis, and the elimination of circulating tumor cells warrant further clinical investigation of IGN311.
文摘A reliable,selective and sensitive liquid chromatography tandem mass spectrometry method was developed and validated for the quantification of lamotrigine in human plasma using lamotrigine13C3,d3 as an internal standard.Analyte and internal standard were extracted from human plasma by solid-phase extraction and detected in positive ion mode by tandem mass spectrometry with electrospray ionization（ESI） interface.Chromatographic separation was performed on a Chromolith s SpeedROD;RP-18e column（50-4.6 mm i.d.） using acetonitrile：570.1 mM ammonium formate solution（90：10,v/v） as the mobile phase at a flow rate of 0.500 mL/min.The calibration curves were linear over the range of 5.02-1226.47 ng/mL with the lower limit of quantitation validated at 5.02 ng/mL.The analytes were found stable in human plasma through three freeze（-20℃）-thaw（ice-cold water bath） cycles and under storage on bench-top in ice-cold water bath for at least 6.8 h,and also in the mobile phase at 10℃ for at least 57h.The method has shown good reproducibility,as the intra-and inter-day precisions were within 3.0%,while the accuracies were within 76.0% of nominal values.The validated LC-MS/MS method was applied for the evaluation of pharmacokinetic and bioequivalence parameters of lamotrigine after an oral administration of 50mg lamotrigine tablet to thirty-two healthy adult male volunteers.
基金National Science Council, Taiwan! under grant !No. NSC-87-2112-M194-005.
文摘Phase evolution and magnetic properties of (Nd_o.95La_0.05)9.5-11Febal.M_2B10.5. where M=Cr, Ti, Nb, V, Mo, Zr, Hf, Ta, Mn or W, melt spun ribbons have been investigated. Almost all the alloy ribbons. except for(Nd_0.95La_0.05)_9.5Fe_78M_2B_10.5(M=Mo and Mn),consist merely two magnetic phases, namely α-Fe and R_2Fe_14B, which display a better combination of _iH_c and magnetic energy product. Remanence (Br) and coercivity (i_H_c) values in the range of 8.0 to 9.1 kG and 9.5 to 18.9 kOe. respectively, can be achieved. Among compositions studied, the Ti and W-substitutions were found to be most effective in increasing the Br and i_H_c, respectively. For a fixed refractory metal substitution, namely, M=C_r, Ti or Nb, an increase in the total rare earth concentration resulted in nanocomposites of small grain sizes and a high volume fraction of the R_2Fe_14B phase, leading to an increase in the magnetic properties.
基金Department of Chemistry,St.Xavier's College,Ahmedabad,India for supporting this work
文摘A rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry（UPLC-MS/MS） method is described for determination of letrozole in human plasma.Following solid phase extraction（SPE） of letrozole and letrozole-d4 on Orochem DVB-LP cartridges,chromatography was performed on Acquity UPLC BEH C_（18）（50 mm × 2.1 mm.1.7 μm） column using methanol-0.1%formic acid in water（85：15,v/v） as the mobile phase.Detection was carried out on a triple quadrupole mass spectrometer with an electrospray source,operated under positive ionization mode.Quantitation of letrozole and letrozole-d4 was done using multiple reaction monitoring（MRM） following the transitions at m/z286.2→217.0 and m/z 290.2→221.0,respectively.The calibration plots were linear through the concentration range of 0.10-100 ng/mL（r^2 ≥ 0.9990） using 100 μL human plasma.The extraction recovery of letrozole ranged from 94.3%to 96.2%and the intra-batch and inter-batch precision was ≤ 5.2%.The method was successfully applied to a bioequivalence study of letrozole after oral administration of2.5 mg tablet formulation to 16 healthy postmenopausal Indian women.The assay reproducibility was also established through incurred sample reanalysis（ISR） of 74 subject samples.
文摘The present paper contains the effects of the ammonium ion, counter ion, solvent and anion being transferred on the solid-liquid phase transfer equilibrium constant of quaternary ammonium salts. The most striking difference between solid-liquid and liquid-liquid phase transfer equilibriums is that the length of alkyl chain shows a large effect on the latter but little on the former This means that the chain length affects only the hydrophobicity, rather than the lipophilicity.Keywords Quaternary ammonium salt, Phase transfer catalysis, Equilibrium constant, Hydrophobicity, Lipophilicity
文摘The lytropic liquid crystals in dodecanic acid diethanolamine (DAD) /n-butanol (C4OH) /octane (n-C8H18) /deuteron (D2O) system were studied to determine the phase regions and were investigated by 2H-NMR spectroscopy,optical polarizing microscope and small-angle X-ray diffraction (SAXD) methods.The results indicate that the lamellar,hexagonal and cubic liquid crystals all exist in the above system.Keeping the weight ratio of DAD and C4OH constant,the microphase Structure,2H quadruple splitting and the interlayer spacing are all changed with the addition of deuteron.
文摘Recently biospecific affinity chromatography has been widely used for the separation and purification of various enzymes and nucleic acids. In this paper, a series of synthetic reactions of solid-liquid phase were carried out on silica surface, using a macroporous(30 mu m), microspherical silica (8 mu m) as the matrix and gamma-aminopropyltriethoxysilane as the activating agent, the nicotinamide adenine dinucleotide(NAD) was bonded through its amino groups to the carboxylic groups of linked phospholipid which was bonded covalently on aminated support. The bonded stationary phase has high thermal stability, and could be used to separate of nucleotides with good resolution.
基金financially supported by the National Natural Science Foundation of China (No. 51402016)the Fundamental Research Funds for the Central Universities (No. FRF-TP-15-008A2)
文摘A one-step sintering process of bauxite raw material from direct mining was completed, and the kinetics of this process was analyzed thoroughly. The results show that the sintering kinetics of bauxite raw material exhibits the liquid-phase sintering behavior. A small portion of impurities existed in the raw material act as a liquid phase. After X-ray diffraction analyses, scanning electron microscopy observations, and kinetics calculations, sintering temperature and heating duration were determined as the two major factors contributing to the sintering process and densification of bauxite ore. An elevated heating temperature and longer duration favor the densification process. The major obstacle for the densification of bauxite material is attributed to the formation of the enclosed blowhole during liquid-phase sintering.
基金sponsored by Shanghai Junshi Biosciences Co.,Ltd.and supported,in part,by National Key R&D Program of China(2018YFC1313300)Science and Technology Program of Guangdong(2019B020227002)+5 种基金CAMS Innovation Fund for Medical Sciences(2019-I2M-5-036)National Natural Science Foundation of China(81930065)Natural Science Foundation of Guangdong Province(2014A030312015)Science and Technology Program of Guangdong(2019B020227002)Science and Technology Program of Guangzhou(201904020046,201803040019,201704020228)Guangdong Basic and Applied Basic Research Foundation(2019A1515110171).
文摘Background:Several programmed cell death ligand 1(PD-L1)/programmed cell death protein 1(PD-1)antibodies have been approved for cancer treatmentworldwide.Their pharmacokinetic and pharmacodynamic characteristics have been reported mainly in western countries,but related data in Chinese patients are limited.This study was conducted to investigate the safety,efficacy,pharmacokinetics,and pharmacodynamics of an anti-PD-1 antibody,toripalimab,in Chinese patients.Methods:A single-center phase I study was conducted in Sun Yat-sen University Cancer Center.Eligible patients were adults with histologically confirmed,treatment-refractory,advanced,solitary malignant tumors.Toripalimab was intravenously infused every 2 weeks in dose-escalating cohorts at 0.3mg/kg,1 mg/kg,3 mg/kg,10 mg/kg,and 240 mg.The study followed standard 3+3 design.Results:Between 15th March 2016 and 27th September 2016,25 patients were enrolled,of whom 3(12.0%),7(28.0%),6(24.0%),6(24.0%),3(12.0%)received 0.3 mg/kg,1 mg/kg,3 mg/kg,10 mg/kg,and 240 mg toripalimab,respectively.After a median follow-up time of 5.0 months(range:1.5-19.8 months),we observed that the commonest treatment-related adverse events(TRAEs)were fatigue(64.0%)and rash(24.0%).No grade 3 or higher TRAEs were observed.No dose-limiting toxicity,treatment-related serious adverse events(SAEs),or treatment-related death occurred.Objective response ratewas 12.5%.The half-life of toripalimabwas 150-222 h after a single dose infusion.Most patients,including those from the 0.3 mg/kg group,maintained complete PD-1 receptor occupancy(>80%)on activated T cells since receiving the first dose of toripalimab.Conclusions:Toripalimab is a promising anti-PD-1 antibody,which was well tolerated and demonstrated anti-tumor activity in treatment-refractory advanced solitary malignant tumors.Further exploration in various tumors and combination therapies is warranted.
基金financially supported by the National Natural Science Foundation of China(Nos.51204054 and 51574084)the Fundamental Research Funds for the Central Universities of China(No.N150204009)the National Basic Research Priorities Program of China(No.2014CB643405)
文摘An orthogonal test was used to optimize the reaction conditions of roasting zinc oxide ore using（NH_4）_2SO_4. The optimized reaction conditions are defined as an（NH_4）_2SO_4/zinc molar ratio of 1.4：1, a roasting temperature of 440°C, and a thermostatic time of 60 min. The molar ratio of（NH_4）_2SO_4/zinc is the most predominant factor and the roasting temperature is the second significant factor that governs the zinc extraction. Thermogravimetric-differential thermal analysis was used for（NH_4）_2SO_4 and zinc mixed in a molar ratio of 1.4：1 at the heating rates of 5, 10, 15, and 20 K·min-1. Two strong endothermic peaks indicate that the complex chemical reactions occur at approximately 290°C and 400°C. XRD analysis was employed to examine the transformations of mineral phases during roasting process. Kinetic parameters, including reaction apparent activation energy, reaction order, and frequency factor, were calculated by the Doyle-Ozawa and Kissinger methods. Corresponding to the two endothermic peaks, the kinetic equations were obtained.
文摘A new theoretical method with generality is proposed to study the statistical properties of the speckle phase. The general expression of the standard deviation of the speckle phase about the first-order statistics is derived according to the relation between the phase and the complex speckle amplitude. The statistical properties of the speckle phase have been studied in the diffraction fields with this new theoretical method.
基金support and necessary facilities provided by Accutest Research Lab,Ahmedabad,to carry out this work
文摘An improved high performance liquid chromatography-tandem mass spectrometry（LC-MS/MS） method has been developed for sensitive and rapid determination of albendazole（ABZ） and its active metabolite,albendazole sulfoxide（ABZSO）,in the positive ionization mode.The method utilized solid phase extraction（SPE） for sample preparation of the analytes and their deuterated internal standards（ISs） from100 μL human plasma.The chromatography was carried out on Hypurity C_（18） column using acetonitrile-2.0 mM ammonium acetate,pH 5.0（80：20,v/v） as the mobile phase.The assay exhibited a linear response over the concentration range of 0.200-50.0 ng/mL for ABZ and 3.00-600 ng/mL for ABZSO.The recoveries of the analytes and ISs ranged from 86.03%-89.66%and 89.85%-98.94%,respectively.Matrix effect,expressed as IS-normalized matrix factors,ranged from 0.985 to 1.042 for the both analytes.The method was successfully applied for two separate studies in healthy subjects using single dose of 400 mg conventional tablets and 400 mg chewable ABZ tablets,respectively.
文摘Ultrasound imaging is the most widely used noninvasive medical imaging modality. Its latest elite concept is Superharmonic Imaging which is the most talked-about future of medical diagnostic ultrasound. In this paper, the computational and analytical study for superharmonic field generation from phased array transducer of 16 × 16 elements is presented. For this, the model preferred, includes the calculation for diffraction effect in frequency domain and nonlinear effect in time domain. The attenuation is included along with the diffraction in frequency domain as well. The comparative analysis of superharmonic field is also carried out with simulated fundamental and second harmonic fields by the same model. Similarly, the comparison with the results from the literature is also reported.
