基于改进NSGA-Ⅱ的交叉口信号配时多目标优化

针对城市交叉口信号配时多目标优化的求解效率问题,设计了一种基于改进NSGA-Ⅱ的城市交叉口信号配时优化方案。该方法采纳车辆延误、停车次数、通行能力3个评价指标设计了多目标信号配时优化模型,并提出了改进的NSGA-Ⅱ(NSGA-Ⅱ-DE)对配时模型进行求解。NSGA-Ⅱ-DE采用DE/Rand/1的全局变异策略对NSGA-Ⅱ算法选择策略进行改进,并设计了种群动态更新算法,提高了算法的收敛速度和求解精度。结果表明改进算法获得了较好的Pareto最优解,通过典型交叉口仿真验证,相对于NSGA-Ⅱ算法,NSGA-Ⅱ-DE方法设计配时方案平均车辆延误优化提升13.42%,排队长度优化提升16.73%,平均停车次数优化提升15.50%,能够实现城市交叉口的最优化控制。

强组合PhaseⅠ－PhaseⅡ次可行方向法

本文对Ｐｏｌａｋ等人的组合ＮａｓｅⅠ－Ⅱ可行方向法进行改进，使之不仅能自动地将初始化阶段（Ｐｈａｓｅｌ）和最优化阶段（ＰｈａｓｅⅡ）统一起来，而且保证了满足不等式约束的函数个数不断叠累递增，故称改进后的算法为强组合ＰｈａｓｅⅠ－ⅡＰｈａｓｅⅡ次可行方向法．本文算法包含了一种新的目标局数非单词的非精确线搜索，它保证了算法产生的点列的任何聚点都是问题的Ｋ－Ｔ的点．

Phase Ⅱ open-label study of recombinant circularly permuted TRAIL as a single-agent treatment for relapsed or refractory multiple myeloma

Background: Despite the recent development of new therapies, multiple myeloma(MM) remains an incurable disease. Thus, new, efective treatments are urgently needed, particularly for relapsed or refractory MM(RRMM). In an earlier phase I study, a novel form of recombinant human Apo2L/tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) that is currently in clinical development for the treatment of hematologic malignancies, i.e., circularly permuted TRAIL(CPT), was well tolerated at a dose of 2.5 mg/kg per day and showed promising preliminary activity in patients with RRMM. This phase II, open-label, multicenter study further investigated the eicacy and safety of 2.5-mg/kg per day CPT as single-agent therapy for patients with RRMM.Methods: Patients with RRMM were treated once daily with CPT(2.5 mg/kg, intravenously) for 14 consecutive days for each 21-day cycle. Clinical response and toxicity were assessed after each treatment cycle.Results: Twenty-seven patients received CPT. Using the European Group for Blood and Marrow Transplantation criteria, we calculated the overall response rate of 33.3% with 1 near-complete response(n CR) and 8 partial responses(PRs). The clinical beneit rate(48.1%) included 1 nCR, 8 PRs, and 4 minimal responses. The most common treatmentrelated adverse events(TRAEs) were fever, aspartate aminotransferase elevation, alanine aminotransferase elevation, leucopenia, rash, neutropenia, and thrombocytopenia. We graded toxicity using the Common Toxicity Criteria for Adverse Events, version 3.0, and determined that 37.0% of patients had at least 1 grade 3–4 TRAE.Conclusions: CPT as a single agent can elicit a response in patients with RRMM and is well tolerated. Further clinical investigation is warranted.

Automatic analytical approach for the determination of 12 illicit drugs and nicotine metabolites in wastewater using on-line SPE-UHPLC-MS/MS

In this study,we developed a novel on-line solid phase extraction(SPE)-ultra-high-performance liquid chromatography tandem mass spectrometry(UHPLC-MS/MS)-based analytical method for simultaneously quantifying 12 illicit drugs and metabolites(methamphetamine,amphetamine,morphine,codeine,6-monoacetylmorphine,benzoylecgonine,3,4-methylenedioxymethamphetamine,3,4-methylenedioxyamphetamine,cocaine,ketamine,norketamine,and methcathinone)and cotinine(COT)in wastewater samples.The analysis was performed by loading 2 m L of the sample onto an Oasis hydrophilic-lipophilic balance cartridge and using a cleanup step(5%methanol)to eliminate interference with a total run time of 13 min.The isotope-labeled internal standard method was used to quantify the target substances and correct for unavoidable losses and matrix effects during the on-line SPE process.Typical analytical characteristics used for method validation were sensitivity,linearity,precision,repeatability,recovery,and matrix effects.The limit of detection(LOD)and limit of quantification(LOQ)of each target were set at 0.20 ng/L and 0.50 ng/L,respectively.The linearity was between 0.5 ng/L and250 ng/L,except for that of COT.The intra-and inter-day precisions were<10.45%and 25.64%,respectively,and the relative recovery ranged from 83.74%to 162.26%.The method was used to analyze various wastewater samples from 33 cities in China,and the results were compared with the experimental results of identical samples analyzed using off-line SPE.The difference rate was between 19.91%and-20.44%,and the error range could be considered acceptable.These findings showed that on-line SPE is a suitable alternative to off-line SPE for the analysis of illicit drugs in samples.

Multicenter phase Ⅱ trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer

AIM To evaluate the efficacy and safety of modified FOLFIRINOX as a second-line treatment for gemcitabine(GEM)-refractory unresectable pancreatic cancer(PC).METHODS This study was a prospective, multicenter, one-arm, open-label, phase Ⅱ trial. Patients with unresectable PC, who showed disease progression during GEMbased chemotherapy were enrolled. All patients were administered FOLFIRINOX with reduced irinotecan and oxaliplatin(RIO; irinotecan 120 mg/m^2 and oxaliplatin 60 mg/m^2), which was set according to the phase Ⅰ study of FOLFIRINOX. The objective response rate(ORR), disease control rate(DCR), progressionfree survival(PFS), overall survival(OS), adverse events were evaluated. Additionally, changes in quality of life(QoL) were assessed using a questionnaire on QoL.RESULTS Between August 2015 and May 2016, a total of 48 patients were enrolled. The median follow-up time was 259 d with a median of 8.5 cycles. The ORR and DCR were 18.8% and 62.5%, respectively, including one patient who showed complete remission. The median PFS was 5.8 mo [95% confidence interval(CI): 3.7-7.9] and median OS was 9.0 mo(95%CI: 6.4-11.6). Neutropenia(64.6%) was the most common grade 3-4 adverse event, followed by febrile neutropenia(16.7%). Although 14.6% of patients experienced grade 3 fatigue, most non-hematologic AEs were under grade 2. In the QoL analysis, the global health status score before treatment was not different from the score at the last visit after treatment(45.43 ± 22.88 vs 48.66 ± 24.14, P = 0.548).CONCLUSION FOLFIRINOX with RIO showed acceptable toxicity and promising efficacy for GEM-refractory unresectable PC. However, this treatment requires careful observation of treatment-related hematologic toxicities.

Phase Transfer Research for Heteropolyanions Containing Cr（Ⅲ），Mn（Ⅳ），Co（Ⅱ），Zn（Ⅱ）

ＰｈａｓｅＴｒａｎｓｆｅｒＲｅｓｅａｒｃｈｆｏｒＨｅｔｅｒｏｐｏｌｙａｎｉｏｎｓＣｏｎｔａｉｎｉｎｇＣｒ（Ⅲ），Ｍｎ（Ⅳ），Ｃｏ（Ⅱ），Ｚｎ（Ⅱ）ＺＨＡＮＧＳｈｕ－ｙｕｎ；ＨＵＡＮＧＲｕ－ｄａｎ；ＹＵＸｉｎ－ｗｕ；ＬＩＢａｉｔａｏａｎｄＷＡＮＧＥｎ－...

Total synthesis of human urotension-Ⅱ by microwave-assisted solid phase method

Human urotension-Ⅱ was synthesized efficiently on Wang resin under microwave irradiation using Fmoc/tBu orthogonal protection strategy. Disulphide bridge was formed on solid phase with the irradiation of microwave, then the whole peptide was cleaved from the resin. The purity of crude peptide cyclized under microwave irradiation was higher than that under room temperature.

PHASE Ⅱ STUDY OF GEMCITABINE COMBINED WITH PLATINUM CHEMOTHERAPY FOR RECURRENT EPITHELIAL OVARIAN CANCER

Objective To evaluate the anti-tumor effect and toxicity of gemcitabine combined with platinum chemotherapy on recurrent epithelial ovarian cancer. Methods Phase Ⅱ study of gemcitabine combined with platinum chemotherapy was carried out in 22 patients with recurrent epithelial ovarian cancer. Median age of patients was 50. 5 years old. Seven patients were platinum-sensitive and 15 patients were platinum-resistant or -refractory. All patients received gemcitabine combined with carboplatin or oxa/iplatin chemotherapy. Patients＇ response rate （RR） and toxicity of gemcitabine combined with platinum chemotherapy were evaluated. Results A total of 98 gemcitabine-based chemotherapy cycles were performed. Total RR was 36. 4%, RR of platinum-sensitive patients was 4/7 and platinum-resistant and -refractory patients was 4/15. The estimated median survival time was 10.0 months （95% CI. 7.0-13.0） after initiation of gemcitabine combined with platinum chemotherapy. There was no significant difference in survival time between platinum-resistant/refractory group and platinum-sensitive group （P = 0. 061 ）. Side effects of gemcitabine combined with platinum chemotherapy were observed in 81.8% of patients. Grade Ⅱ/Ⅲ anemia （54. 5% ） and grade Ⅲ/Ⅳ neutropenia （54. 5% ） were most common toxicities. Ten （45.5%） patients had to delay their chemotherapy cycles or reduce the dose of chemotherapeutic drugs because of the severe side effects. Fourteen （63.6%） patients received granulocyte colony-stimulating factor to relieve neutropenia, and 8 （ 36. 4% ） patients received component blood transfusion to treat anemia or thrombocytopenia. There was no treatment-associated death. Conclusion Gemcitabine combined with platinum chemotherapy appears to be an effective and well-tolerant treatment for recurrent epithelial ovarian cancer, including platinum-resistant or -refractory diseases.

Self-reliance and Innovation of Qinshan Phase Ⅱ NPP Project

This article mainly describes the self-reliance and innovation of Qinshan nuclear power project of phase II,in-between it contains new reactor core design,as well as related experimental and calculation analysis,especially for new reactor design produced fluid-induced vibration model test,theoretical analysis and testing in-built reactor;aiming at two-loop NSSS a series improvement made for safety systems and related safety analysis to enhance their reliability and redundancy;according to specialty of two-loop NSSS an optimization made for NPP parameters and design of related equipments,for the purpose to make the output of NPP maximal;design of main reactor building and T-G building also improved according to characteristics of two-loop NSSS and site conditions.CRDM and refueling machine are researched and manufactured on base of self-reliance,their performance are better than design requirements,large portion of key equipments are localized through different way.In construction first time realized the integrated erection of containment dome.During the commissioning non-nuclear steam driving of T-G set,as well as 500 kV high voltage rising using emergent diesel generator,etc.are carried out.In period of operation still continuous innovation and improvement are made,so that to keep the good record of operation.

STUDY ON DETERMINATION OF TRACE Cu（Ⅱ） BY DDCT CHELATING RESIN PRECONCENTRATION AND THIN LAYER RESIN PHASE SPECTROPHOTOMETRY

A new method for determination of Cu（Ⅱ） by DDCT chelating resin preconcentration and thin layer resin phase spectrophotometry was developed. The method has a high sensitivity （ε455= 3.6×10^5L/mol·cm）, which is 33 times higher than that of liquid phase spectrophotometry. It has a good selectivity （most coexisting ions could not influence determination） and an ideal precision [30μg Cu（Ⅱ）, n=6, RSD= l.67%]. The content of Cu（Ⅱ） in water, high purity rare earth and its oxide was determined. The detection limit of Cu（Ⅱ） is 5.3μg/L , and the linear range is 0-7.2μg/ml. The result is satisfactory.

TITE(e)-U-Keyboard两阶段Ⅰ/Ⅱ期试验设计研究

目的针对肿瘤靶向制剂和细胞免疫疗法治疗效应延迟的问题,基于Ⅰ/Ⅱ期试验设计框架,构建创新试验设计方法TITE(e)-U-Keyboard。方法采用二项近似似然法纳入尚未观测到的有效性结局信息,构建近似分布,辅助决策,并将TITE(e)-U-Keyboard同Ⅰ/Ⅱ期试验设计方法U-BOIN、BOIN12从多个角度进行模拟比较研究。结果模拟结果显示在考虑有效性结局延迟的情况下三种方法的OBD选择准确率及最优剂量分配受试者数相当,但TITE(e)-U-Keyboard所需试验时长最短;敏感性分析表明有效性观察窗会对TITE(e)-U-Keyboard试验时长产生影响,且随着有效性观察窗的增加而增加。结论TITE(e)-U-Keyboard在保持良好试验设计性能的同时显著缩短了试验时长,可以解决Ⅰ/Ⅱ期临床试验中治疗效应延迟的问题,加速临床试验进程。

Analysis of Bacterial Communities Present in Agaricus bisporus Phase Ⅱ Compost Using Amplified Ribosomal DNA Restriction Analysis(ARDRA)(Ⅱ)——Analysis of Bacterial Communities

Changes in the bacterial communities inhabiting Agaricus bisporus compost during Phase Ⅱ treatment were monitored using amplified rDNA restriction analysis(ARDRA).Sequence analysis data indicated that the bacterial communities associated with the compost samples were far richer in composition when determined by ARDRA compared with traditional methods based on bacterial isolation.Furthermore,the composition of the communities,especially in terms of the dominant bacteria during each of the four treatment stages(beginning of Phase Ⅱ,after pasteurization,5 days aeration,end of Phase Ⅱ,respectively),were very different.Restriction endonuclease digestion of mainly bacterial clones from four 16S rDNA libraries,C1,C3,C6 and C7,previously constructed on the basis of 16S rDNA fragments amplified from the four different stages of the Phase Ⅱ composting process,revealed the presence of unique microbial types.Thermophilic bacteria belonging to the Bacilli,and previously unreported strains of Trichococcus,Planococcus,Caryophanon,and subclass γ-Proteobacteria,were identified among the clones from the compost sampled during the aeration period(C6).Bacteria belonging to Thermus thermophilus and subclass α-Proteobacteria were detected in C1 and C7 composts sampled at the beginning and the end of Phase Ⅱ,respectively.Clones of some uncultured bacteria were also scored.

分散固相萃取净化-超高效液相色谱-串联质谱法测定蜂蜜中双甲脒、杀虫脒及其代谢物

该研究建立了分散固相萃取-超高效液相色谱-串联质谱(dispersive solid phase extraction-ultra-performance liquid chromatography,UPLC-MS-MS)检测蜂蜜中双甲脒、杀虫脒及其代谢物残留的分析方法。蜂蜜样品2 g加入10 mL水溶液充分混匀,经1%(体积分数)氨化乙腈超声辅助提取后离心,利用N-丙基乙二胺、C18、氨基键合硅胶混合材料进行分散固相萃取净化,采用ACQUITY UPLC BEH C18(2.1 mm×50 mm,1.7μm)色谱柱分离,以甲醇和0.1%(体积分数)甲酸水溶液为流动相进行梯度洗脱,多反应监测模式正离子扫描分析。6种农药及其代谢物平均回收率为84.1%~113.8%,相对标准偏差为0.9%~6.0%,检出限为0.2~0.8μg/kg,定量限为0.7~2.5μg/kg。实验结果表明该方法快速简便、灵敏度高,适用于蜂蜜中双甲脒、杀虫脒及其代谢物残留同时分析。

国产奥沙利铂治疗大肠癌Ⅱ期临床研究

目的:评价国产注射用奥沙利铂单药及与5-氟尿嘧啶(5-Fu)-四氢叶酸(CF)联合用于治疗大肠癌的疗效及毒副反应。方法:收治带瘤大肠癌患者49例,按随机方法,分别入单药组11例(单用奥沙利铂),联合组20例(奥沙利铂+5—Fu+CF),和对照组18例(5—Fu+CF)。结果:单药组有效率27.3％,联合组30.0％,对照组5.6％,单药组和联合组疗效高于对照组,且奥沙利铂对大肠癌常见转移部位如肝脏、腹腔淋巴结、盆腔及肺脏均可见临床疗效,毒副反应主要为神经感觉异常,其中重度异常单药组为9％,联合组为10％。结论:国产注射用奥沙利铂单用或联合5—Fu、CF治疗大肠癌疗效肯定,耐受性良好,值得临床进一步研究和扩大应用。

多联吡啶螯合物反相高效液相色谱法分离测定铜(Ⅱ)、钴(Ⅱ)、汞(Ⅱ)

以三联吡啶衍生物６，６”－二甲基－４＇－苯基－２，２＇：６＇，２”－三联吡啶（ＴＰＹ）作柱前显色剂，于ＡｃｃＱ－Ｔａｇ柱上，用内含２．０×１０～（－６）ｍｏｌ／Ｌ ＴＰＹ和０．６ ｍｏｌ／Ｌ ＮａＡｃ－ＨＡｃ缓冲溶液（ｐＨ＝３．５）的甲醇－水溶液（５５：４５，Ｖ／Ｖ）作流动相，流速为１．０ ｍＬ／ｍｉｎ，并以紫外－可见检测器于３１０ｎｍ处进行检测，开发了一种 ＲＰ－ＨＰＬＣ法同时分离测定铜（Ⅱ）、钴（Ⅱ）、汞（Ⅱ）的方法。该方法简便快速，灵敏度高，对于铜、钴、汞的检测限分别是０．００２０、０．００５５和０．００４０ｍｇ／Ｌ。用于实际样品测定，结果满意。

2-(2-噻吩偶氮)-5-二乙氨基酚反相液相色谱法分离测定铜(Ⅱ)、钴(Ⅱ)、镍(Ⅱ)

本文以2-(2-噻吩偶氮)-5-二乙氨基酚(简称TADAP)作柱前显色剂,反相色谱法分离测定铜(Ⅱ)、钴(Ⅱ)、镍(Ⅱ)离子。用含有1.5×10^(-4)mol/L的TADAP,0.1mol/L氯化锂和0.1mol/L乙酸盐(pH4)的甲醇(60％)-水(40％)溶液作为流动相,流量为0.9ml/min,紫外-可见检测器检测波长为545nm。在此条件下,铜(Ⅱ)、钴(Ⅱ)、镍(Ⅱ)螯合物得到最佳分离,并定量测定了茶叶中铜、钴、镍的含量,与原子吸收分光光度法测定,得到一致的结果。

国产唑来膦酸治疗肿瘤高钙血症多中心Ⅱ期临床观察

目的:评价国产注射用唑来膦酸治疗肿瘤高钙血症的临床疗效和安全性。方法:采用多中心、开放临床研究对15例肿瘤性高钙血症患者给予唑来膦酸4mg静脉滴注15min治疗,在28天内定期观察血钙的变化和不良反应。结果:1例患者因依从性差出组,可评价疗效14例。有效缓解率,即校正血钙降至正常,为100%(14/14),有效缓解中位时间为5.07天,缓解的中位维持时间22.30天。不良反应主要有轻中度发热。结论:国产注射用唑来膦酸能够快速、有效、持久的降低恶性肿瘤高钙血症,使用安全、方便。

国产英卡膦酸二钠治疗恶性肿瘤骨转移疼痛或/和高钙血症的Ⅱ期临床研究

目的:评价国产英卡膦酸二钠治疗恶性肿瘤骨转移疼痛或/和高钙血症的疗效和安全性。方法:采用多中心、随机阳性药平行对照研究方法,将212例恶性肿瘤骨转移病人分为试验组和对照组,每组106例,分别给予国产英卡膦酸二钠10 mg与帕米膦酸钠90 mg,观察其疗效和毒副作用。高钙血症治疗采用非随机临床研究。结果:国产英卡膦酸二钠治疗骨转移疼痛的有效率为70.19%,生活质量改善有效率为50.96%。对照组骨转移疼痛治疗有效率为67.62%,生活质量改善有效率为51.43%。试验组在疼痛缓解率和生活质量改善上与对照组均无显著差异。试验组不良反应发生率明显低于对照组(26.42%vs46.23%),主要为Ⅰ、Ⅱ度发热,两组有非常显著差异(P<0.01)。6例肿瘤骨转移伴高钙血症的病人使用英卡膦酸二钠后,有3例第3天血钙降至正常,2例第5天血钙降至正常,1例第14天血钙降至正常。结论:国产英卡膦酸二钠治疗恶性肿瘤骨转移疼痛疗效显著,安全可靠,治疗高钙血症有效,值得临床推广使用。

葛酮通络胶囊治疗脑梗死恢复期瘀血痹阻脉络证的Ⅱ期临床研究

目的评价葛酮通络胶囊治疗脑梗死恢复期瘀血痹阻脉络证的安全性及有效性。方法随机、双盲双模拟、阳性平行对照、多中心研究方法进行葛酮通络胶囊的Ⅱ期临床试验。受试者共210例,A组104例给予葛酮通络胶囊500 mg+安慰剂,2次/d;B组106例给予血塞通片100 mg+安慰剂,2次/d。治疗28 d后,观察并评价其临床疗效和安全性。结果 A组和B组中风病总有效率分别为88%和77%,组间比较有显著性差异(P=0.018)。A组和B组中医证候总有效率分别为84%和74%,组间比较无显著性差异(P>0.05)。治疗前2组中风病病类量化评分比较无显著性差异(P>0.05),治疗中与治疗后组间比较有显著性差异(P=0.045,P=0.001)。2组均能改善全血黏度(低切)、纤维蛋白原、血小板聚集率等指标(P<0.01或0.05),同时A组对血浆黏度有明显改善作用(P=0.008)。2组都没有出现不良事件。结论葛酮通络胶囊治疗脑梗死恢复期瘀血痹阻脉络证安全有效。

莱菔硫烷诱导Ⅱ相酶表达保护大鼠脊髓运动神经元

目的探讨Ⅱ相酶诱导剂莱菔硫烷(SF)对运动神经元的保护作用。方法应用SD乳鼠脊髓体外器官型培养模型,随机分成3组:对照组、THA组和SF联合THA组。用免疫组化法检测运动神经元数目,用Westernblot法检测Ⅱ相酶蛋白水平。结果THA干预后运动神经元数目较对照组明显减少(P<0.05,n=10～15),而应用SF预处理48h,再给予SF和THA联合处理3周后,运动神经元数目较THA组明显增加(P<0.05,n=10～15),同时Ⅱ相酶NQO-1和HO-1表达明显升高(P<0.05,n=3)。结论SF通过诱导Ⅱ相酶NQO-1和HO-1的表达,可以有效预防THA引起的运动神经元损伤。