The monolithic foamed propellants with high densities were prepared by casting and two-step foaming processes.Glycidyl azide polymer(GAP)and isocyanate were used as the binder system and 2,4,6,8,10,12-hexanitro-2,4,6,...The monolithic foamed propellants with high densities were prepared by casting and two-step foaming processes.Glycidyl azide polymer(GAP)and isocyanate were used as the binder system and 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane(HNIW,CL-20)was employed as the energetic component.The newly designed formulation containing 60%CL-20 produced a force constant of 1077 J/g and low flame temperature of 2817 K.Two foamed propellants with densities of 1.32 g/cm^(3)and 1.53 g/cm^(3)were fabricated by a confined foaming process and examined by closed bomb tests.The results revealed that porosity significantly affects burning performance.A size effect on combustion behaviors was observed for the foamed propellant with 5.56%porosity,and a double-hump progressive dynamic vivacity curve was obtained.At last,the 30 mm gun test was carried out to demonstrate the interior ballistic performance,and the muzzle velocity increased by 120 m/s at the same maximum chamber pressure when monolithic propellant was added in the charge.展开更多
BACKGROUND Congenital nephrogenic diabetes insipidus(CNDI)is a rare hereditary disorder.It is associated with mutations in the arginine vasopressin receptor 2(AVPR2)gene and aquaporin 2(AQP2)gene,and approximately 270...BACKGROUND Congenital nephrogenic diabetes insipidus(CNDI)is a rare hereditary disorder.It is associated with mutations in the arginine vasopressin receptor 2(AVPR2)gene and aquaporin 2(AQP2)gene,and approximately 270 different mutation sites have been reported for AVPR2.Therefore,new mutations and new manifestations are crucial to complement the clinical deficiencies in the diagnosis of this disease.We report a case of a novel AVPR2 gene mutation locus and a new clinical manifestation.CASE SUMMARY We describe the case of a 48-d-old boy who presented with recurrent fever and diarrhea 5 d after birth.Laboratory tests showed electrolyte disturbances and low urine specific gravity,and imaging tests showed no abnormalities.Genetic testing revealed a novel X-linked recessive missense mutation,c.283(exon 2)C>T(p.P95S).This mutation results in the substitution of a proline residue with a serine residue in the AVPR2 protein sequence.The diagnosis of CNDI was confirmed based on the AVPR2 gene mutation.The treatment strategy for this patient was divided into two stages,including physical cooling supplemented with appropriate amounts of water in the early stage and oral hydrochlorothiazide(1-2 mg/kg)after a clear diagnosis.After follow-up of one and a half years,the patient gradually improved.CONCLUSION AVPR2 gene mutations in new loci and new clinical symptoms help clinicians understand this disease and shorten the diagnosis cycle.展开更多
Objective: To compare the pharmacokinetic differences of the main components of Naoxintong capsule(NXTC) in normal and acute blood stasis rats. Materials and Methods: Rats were subcutaneously injected with adrenaline ...Objective: To compare the pharmacokinetic differences of the main components of Naoxintong capsule(NXTC) in normal and acute blood stasis rats. Materials and Methods: Rats were subcutaneously injected with adrenaline hydrochloride twice;during the two subcutaneous injections, the rats were placed in ice water for 4 min to reproduce the model rat of acute blood stasis. The normal and acute blood stasis rats were administrated a 5.04 g/kg dose of NXTC suspension. Then, blood samples were collected from the posterior retinal venous plexus at different time points. Plasma concentrations of four major bio-active components including caffeic acid, ferulic acid, formononetin, and tanshinone IIA in NXTC were measured using ultra-performance liquid chromatography coupled with triple-quadrupole mass spectrometry. Phoenix Win Nonlin v6.2 software was used to calculate the pharmacokinetic parameters. Results: Compared with the normal rats, the acute blood stasis rats showed a significant decrease in C_(max) of ferulic acid and formononetin, AUC_(all) of caffeic acid and ferulic acid, and AUC_(INF_obs) of ferulic acid. Conversely, an increase in the Vz_F_obs and MRT_(last) of ferulic acid and caffeic acid was observed. These findings demonstrate that the absorption of the four NXTC components was weakened in the acute blood stasis rats and that the elimination time was prolonged. Conclusions: The significant difference in some parameters of the four NXTC components between the normal and acute blood stasis rats might be caused by an increase in blood viscosity and the subsequent slowing down of blood flow in the acute blood stasis rats. The pharmacokinetic study conducted in pathological state can provide important information and scientific basis for further rational clinical application of NXTC.展开更多
When the historical data of the early phase trial and the interim data of the Phase II trial are avail-able,we should use them to give a more accurate prediction in both futility and efficacy analysis.The predictive p...When the historical data of the early phase trial and the interim data of the Phase II trial are avail-able,we should use them to give a more accurate prediction in both futility and efficacy analysis.The predictive power is an important measure of the practical utility of a proposed trial,and it is better than the classical statistical power in giving a good indication of the probability that the trial will demonstrate a positive or statistically significant outcome.In addition to the four predic-tive powers with historical and interim data available in the literature and summarized in Table 1,we discover and calculate another four predictive powers also summarized in Table 1,for one-sided hypotheses.Moreover,we calculate eight predictive powers summarized in Table 2,for the reversed hypotheses.The combination of the two tables gives us a complete picture of the pre-dictive powers with historical and interim data for futility and efficacy analysis.Furthermore,the eight predictive powers with historical and interim data are utilized to guide the futility analysis in the tamoxifen example.Finally,extensive simulations have been conducted to investigate the sensitivity analysis of priors,sample sizes,interim result and interim time on different predictive powers.展开更多
文摘The monolithic foamed propellants with high densities were prepared by casting and two-step foaming processes.Glycidyl azide polymer(GAP)and isocyanate were used as the binder system and 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane(HNIW,CL-20)was employed as the energetic component.The newly designed formulation containing 60%CL-20 produced a force constant of 1077 J/g and low flame temperature of 2817 K.Two foamed propellants with densities of 1.32 g/cm^(3)and 1.53 g/cm^(3)were fabricated by a confined foaming process and examined by closed bomb tests.The results revealed that porosity significantly affects burning performance.A size effect on combustion behaviors was observed for the foamed propellant with 5.56%porosity,and a double-hump progressive dynamic vivacity curve was obtained.At last,the 30 mm gun test was carried out to demonstrate the interior ballistic performance,and the muzzle velocity increased by 120 m/s at the same maximum chamber pressure when monolithic propellant was added in the charge.
文摘BACKGROUND Congenital nephrogenic diabetes insipidus(CNDI)is a rare hereditary disorder.It is associated with mutations in the arginine vasopressin receptor 2(AVPR2)gene and aquaporin 2(AQP2)gene,and approximately 270 different mutation sites have been reported for AVPR2.Therefore,new mutations and new manifestations are crucial to complement the clinical deficiencies in the diagnosis of this disease.We report a case of a novel AVPR2 gene mutation locus and a new clinical manifestation.CASE SUMMARY We describe the case of a 48-d-old boy who presented with recurrent fever and diarrhea 5 d after birth.Laboratory tests showed electrolyte disturbances and low urine specific gravity,and imaging tests showed no abnormalities.Genetic testing revealed a novel X-linked recessive missense mutation,c.283(exon 2)C>T(p.P95S).This mutation results in the substitution of a proline residue with a serine residue in the AVPR2 protein sequence.The diagnosis of CNDI was confirmed based on the AVPR2 gene mutation.The treatment strategy for this patient was divided into two stages,including physical cooling supplemented with appropriate amounts of water in the early stage and oral hydrochlorothiazide(1-2 mg/kg)after a clear diagnosis.After follow-up of one and a half years,the patient gradually improved.CONCLUSION AVPR2 gene mutations in new loci and new clinical symptoms help clinicians understand this disease and shorten the diagnosis cycle.
基金supported by the National Science and Technology Major Project of China “Key New Drug Creation and Manufacturing Program” 2015ZX09501004-001-007National Natural Science Foundation of China 82004082Top talent training project of TCM in Henan Province。
文摘Objective: To compare the pharmacokinetic differences of the main components of Naoxintong capsule(NXTC) in normal and acute blood stasis rats. Materials and Methods: Rats were subcutaneously injected with adrenaline hydrochloride twice;during the two subcutaneous injections, the rats were placed in ice water for 4 min to reproduce the model rat of acute blood stasis. The normal and acute blood stasis rats were administrated a 5.04 g/kg dose of NXTC suspension. Then, blood samples were collected from the posterior retinal venous plexus at different time points. Plasma concentrations of four major bio-active components including caffeic acid, ferulic acid, formononetin, and tanshinone IIA in NXTC were measured using ultra-performance liquid chromatography coupled with triple-quadrupole mass spectrometry. Phoenix Win Nonlin v6.2 software was used to calculate the pharmacokinetic parameters. Results: Compared with the normal rats, the acute blood stasis rats showed a significant decrease in C_(max) of ferulic acid and formononetin, AUC_(all) of caffeic acid and ferulic acid, and AUC_(INF_obs) of ferulic acid. Conversely, an increase in the Vz_F_obs and MRT_(last) of ferulic acid and caffeic acid was observed. These findings demonstrate that the absorption of the four NXTC components was weakened in the acute blood stasis rats and that the elimination time was prolonged. Conclusions: The significant difference in some parameters of the four NXTC components between the normal and acute blood stasis rats might be caused by an increase in blood viscosity and the subsequent slowing down of blood flow in the acute blood stasis rats. The pharmacokinetic study conducted in pathological state can provide important information and scientific basis for further rational clinical application of NXTC.
基金The research was supported by National Social Science Fund of China[grant number 21XTJ001].
文摘When the historical data of the early phase trial and the interim data of the Phase II trial are avail-able,we should use them to give a more accurate prediction in both futility and efficacy analysis.The predictive power is an important measure of the practical utility of a proposed trial,and it is better than the classical statistical power in giving a good indication of the probability that the trial will demonstrate a positive or statistically significant outcome.In addition to the four predic-tive powers with historical and interim data available in the literature and summarized in Table 1,we discover and calculate another four predictive powers also summarized in Table 1,for one-sided hypotheses.Moreover,we calculate eight predictive powers summarized in Table 2,for the reversed hypotheses.The combination of the two tables gives us a complete picture of the pre-dictive powers with historical and interim data for futility and efficacy analysis.Furthermore,the eight predictive powers with historical and interim data are utilized to guide the futility analysis in the tamoxifen example.Finally,extensive simulations have been conducted to investigate the sensitivity analysis of priors,sample sizes,interim result and interim time on different predictive powers.
