Deformation behavior and processing maps of Mg-Zn-Y alloy containing Ⅰ phase at elevated temperatures

The microstructure and mechanical properties of extruded Mg-Zn alloy containing Y element were investigated in temperature range of 300-450°C and strain rate range of 0.001-1 s-1 through hot compression tests.Processing maps were used to indicate optimum conditions and instability zones for hot deformation of alloys.For Mg-Zn and Mg-Zn-Y alloys,peak stress,temperature and strain rate were related by hyperbolic sine function,and activation energies were obtained to be 177 and 236 kJ/mol,respectively.Flow curves showed that the addition of Y element led to increase in peak stress and decrease in peak strain,and indicated that DRX started at lower strains in Mg-Zn-Y alloy than in Mg-Zn alloy.The stability domains of Mg-Zn-Y alloy were indicated in two domains as 1)300°C,0.001 s-1;350°C,0.01-0.1 s-1 and 400°C,0.01 s-1 and 2)450°C,0.01-0.1 s-1.Microstructural observations showed that DRX was the main restoration mechanism for alloys,and fully dynamic recrystallization of Mg-Zn-Y alloy was observed at 450°C.The instability domain in Mg-Zn-Y alloy was located significantly at high strain rates.In addition,the instability zone width of Mg-Zn and Mg-Zn-Y alloys increased with increasing strain,and cracks,twins and severe deformation were considered in these regions.

循环热力作用岩石I型断裂试验方法及其可行性研究

探明岩石在循环应力和循环温度作用后的断裂特性对于保障地下洞室压缩空气储能这一“双碳”工程的稳定性具有重要现实意义。提出了循环热力作用岩石I型断裂试验方法并对该试验方法的可行性进行了研究。为研究经循环应力和循环温度作用后的岩石受力变形特性和I型断裂特性,设计了相应的带裂缝岩石试件,并提出了相应的试验步骤;采用COMSOL Multiphysics软件对设计的试件进行升降温和单轴压缩试验模拟,采用相场断裂方法模拟三点弯梁断裂试验,获得相应热力响应和裂缝路径,论证试验方法的适用性与可行性。数值模拟结果表明,所提出的试验方法可获得与理论解误差极小的温度场、应力场和裂缝扩展路径,可只对一个试件进行试验而获得循环热力作用过程中的岩石受力变形特性以及循环后的I型断裂特性。

A phaseⅠtrial of an oral subtype-selective histone deacetylase inhibitor,chidamide,in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer

Objective： This phase I study was to evaluate safety, maximum tolerated dose, pharmacokinetics and preliminary antitumor activity of chidamide, a novel subtype-selective histone deacetylase （HDAC） inhibitor, in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer （NSCLC）. Methods： Ten patients received oral chidamide 20, 25, or 30 mg twice per week continuously with paclitaxel （175 mg/m2） and carboplatin [area under the curve （AUC） 5 mg/mL/min] administered in a 3-week cycle. Patients with response and stable disease after four cycles maintained chidamide monotherapy until disease progression or unacceptable toxicity. Blood samples were collected for pharmacoldnetic analysis after the first single oral of chidamide and first combination treatment in cycle 1 from all patients. Results： Two dose-limiting toxicities were recorded in the 30 mg cohort, including thrombocytopenia and prolonged neutropenia in the first cycle. Grade 3/4 neutropenia in any cycle was observed in all patients, but was not associated with significant complications. Other grade 3/4 hematologic toxicities included thrombocytopenia and leucopenia. No significant changes were observed in pharmacokinetic parameters for both chidamide and paclitaxel. One patient in the 20 mg cohort had confirmed partial response （PR）. Two out of 5 patients with brain metastases had intracranial complete remission after 4-cycle treatment. Conclusions： Chidamide combined with paclitaxel and carboplatin was generally tolerated without unanticipated toxicities or clinically relevant pharmacokinetic interactions. The recommended dose for chidamide in this combination was established at 20 mg, and a phase II trial is ongoing with this regimen in patients with advanced NSCLC.

Phase I study of chimeric anti-CD20 monoclonal antibody in Chinese patients with CD20-positive non-Hodgkin＇s lymphoma

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.

The evolution of phase I trials in cancer medicine:a critical review of the last decade

The advent of targeted therapies, combined with an unsustainable rate of failure in oncology drug development, has resulted in a number of new approaches to clinical trials. Early clinical trials are no exception, with efforts to improve the eventual success rate of late stage trials through evolving phase I trial methodologies, the addition of extensive pharmacodynamic studies, and early adoption of patient selection strategies. Unfortunately, some of these new approaches have met with mixed results. Furthermore, no clear metrics are available to determine whether these designs are more successful than previous strategies. This review examines the evolution of phase I trials and draws upon several examples of strategies that have been successful as well as those that have not, and outlines a pragmatic approach to phase I trials as our understanding of the molecular biology of individual malignancies emerges.

Safety and immunogenicity of human papillomavirus-16/18 AS04-adjuvanted vaccine in healthy Chinese females aged 15 to 45 years:a phase Ⅰ trial

Globally,about 70% of cervical cancers are associated with human papillomavirus (HPV)-16 or HPV-18 infection.A meta-analysis of epidemiologic studies in China showed that HPV was present in 98% of cervical cancer samples.The HPV-16/18 AS04-adjuvanted vaccine Cervarix has shown a high level of protection against HPV-16/18 infections and associated cervical lesions.This phase Ⅰ trial (NCT00549900) assessed the safety,tolerability,and immunogenicity of the vaccine in Chinese.Thirty healthy Chinese females,aged 15 to 45 years with a median age of 29.5 years,received three doses of Cervarix in Months 0,1,and 6.Safety was assessed via recording solicited local and systemic symptoms within 7 days and unsolicited symptoms within 30 days after each vaccination.Serious adverse events,new onset of chronic diseases,and other medically significant conditions were recorded throughout this trial.As an exploratory objective,HPV-16/18 antibody titers were determined by enzyme-linked immunosorbent assay in serum samples collected in Months 0 and 7.Pain at the injection site was the most frequently reported local symptom.Two subjects reported medically significant adverse events.Both cases were assessed as unrelated to vaccination by the investigator.In Month 7,100% seroconversion was observed for both anti-HPV-16 and anti-HPV-18 with high geometric mean antibody titers.HPV-16/18 AS04-adjuvanted vaccine,evaluated for the first time in Chinese females,was generally well tolerated and immunogenic,as previously shown in global studies.

Soybean Lecithin Acts as both Absorption Enhancer and Oily Phase in an Insulin-loaded Emulsion System for Transmucosal Delivery

An insulin-loaded emulsion system （IES） was developed as a hypoglycaemic drug for transmucosal delivery. The selected formulation was a stable oil/water emulsion system. The particles in the emulsion system were distributed evenly, and the particle size ranged from 20 to 260 nm（ average size ： 67.5 nm ）. Soybean lecithin played an important role in the emulsion system due to its abilities of acting as both absorption enhancer for insulin uptake through sublingual mucosa and oily phase for the emulsion system. The laser confocal scanning microscopic（LCSM） study showed that FITC-labelled insulin could penetrate the sublingual mucosa of rabbits, and the phase diagrams of the emulsion system suggested that soybean lecithin could take the place of oily phase to construct a stable emulsion system even if the traditional oil was absent. The applications of soybean lecithin as pharmaceutical biomaterial were extended for the further usage by present studies.

基于条件加权似然方法的BOIN12设计的改进研究

目的基于条件加权似然方法对BOIN12设计进行改进,解决试验药物毒性和有效性出现延迟的情况下的最优剂量探索问题。方法利用条件加权似然方法给出延迟情况下的似然函数,对毒性率和条件有效率进行估计。通过模拟将改进后的BOIN12设计与其他Ⅰ-Ⅱ期设计方法进行比较,评估其性能。结果模拟研究表明,在多个不同场景下,改进后的设计仍然具有优良的统计性能,同时大大缩短了试验时长。结论改进后的设计可以解决Ⅰ-Ⅱ期试验中的毒性和有效性同时延迟问题。

A phase I radiation dose escalation of stereotactic body radiotherapy for malignant lung tumors

Objectives: This Phase I study determines the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT) for lung tumors. Methods: Eli- gible patients had biopsy proven cancer with a maxi- mum tumor size ≤ 5 cm. Total doses were escalated from 40 to 48, then to 56 Gy, delivered in 4 equal fractions administered 2 to 3 times per week on an IRB approved protocol. SBRT was administered us- ing 5 to 9 fixed beam arrangements with CT loca- lization. Internal target volumes (ITV) were based on breath hold scans or 4D CT simulation. The planning target volume (PTV) was defined as the ITV with a uniform 5 mm expansion. Dose limiting toxicity (DLT) was defined as any grade 3 or higher toxicity using the Radiation Therapy Oncology Group (RTOG) common toxicity criteria (CTC). Results: Between April 2004 and February 2008, 18 patients received the prescribed treatment (40 Gy n = 6, 48 Gy n = 7, 56 Gy n = 5). Seventeen of 18 patients had non-small cell lung cancer (1 with rectal cancer), four of whom were treated for an oligometastasis. The median age of the patients was 68, while the median Karnofsky performance status was 90. The mean tumor size was 2.6 cm (range 0.9 to 4.5 cm). One grade 3 pulmonary event occurred (at 48 Gy dose level) immediately following treatment with the onset of fever and shortness of breath that responded to antibiotics. No other DLTs occurred. Conclusions: SBRT utilizing patient specific target volumes without gating appears safe. The maximum tolerated dose was not reached.

A phase I study with Satraplatin and simultaneous chest radiation for non-small cell lung cancer

Introduction: Satraplatin has been given in combination therapy for lung cancer to utilize its radio-sensitizing properties. The optimal dose of satra-platin given concurrently with radiation therapy for locally advanced non-small cell lung cancer (NSC-LC) has not been defined. This phase I trial attempts to identify a maximally tolerated dose (MTD) and dose limiting toxicity (DLT) for Satraplatin given con-currently with radiation for locally advanced N-SCLC. Patients and Methods: 15 patients with histologically confirmed Stage IIIA/B NSCLC entered onto this study with four dose escalations (10 to 40 mg daily) of Satraplatin. Eligibility included patients with NSCLC and one of the following criteria: 1) previously untreated, inoperable disease and planned to receive radiation therapy to primary disease site;2) previously resected disease with mediastinal relapse;or 3) metastatic disease in no more than one distant site. Results: The most common toxicities reported were all grades of fatigue (n = 9), nausea (n = 9), constipation (n = 7), fever (n = 7), and vomiting (n = 6). No DLT at the 1st, 2nd, and 3rd dose levels was identified. At the 4th dose level, one patient developed grade III elevation of liver function tests (LFTs) and a second patient developed grade III diarrhea with fever requiring hospitalization. There were 8 partial responses out of 11 evaluable patients for response (RR 67%). Conclusion: Elevated LFTs and diarrhea appear to be the principal DLTs of concurrent daily oral Satraplatin and thoracic radiation in the outpatient setting. The MTD of concurrent Satraplatin with thoracic radiation therapy appears to be 40 mg daily.

A phase I safety and efficacy study of the mammary aspirate specimen cytology test device for collection of spe-cimens for exfoliative cytopathology of the breast ducts

Background: The ability to identify asymptomatic women at high risk for breast cancer using known pre-malignant changes in exfoliative cytopathology of nipple aspirate fluid is of clinical importance. Exfoliative cytopathology of Nipple Aspirate Fluid (NAF) has been shown to be an important adjunct to the currently accepted standard of medical care, i.e. mammography, coupled with physical examination, for the diagnosis of breast cancer. This is especially important for the subset of women aged 18-50 who are not identified as “high risk”, and therefore, for whom mammography is not routinely recommended. The objective of this study was to determine if a new, patented Class II medical device, the Mammary Aspirate Specimen Cytology Test (MASCT) System, designed to collect NAF for subsequent cytological examination is safe and effective. Methods: The MASCT medical device is a modified breast pump and was used to obtain bilateral specimens from 34 healthy, non-pregnant, female subjects for cytopathological examination. A conventional breast disease work-up was performed (medical history/risk factor collection, clinical breast examination and mammogram) and NAF specimens collected. Specimen weight was measured and a cytopathological examination was performed. Vital signs measurements, clinical laboratory analysis, and adverse event reporting were performed. Results: Based on cytopathological evaluation and/or measurable weight changes on the specimen collection membrane filter, all breasts evaluated (100%) yielded nipple aspirate fluid. Specimen weights ranged from <1 to 37 mg and all specimens evaluated cytopathologically were deemed to be clinically useful. One patient’s specimen was not available for cytopathological examination due to specimen mishandling, resulting in 60 breasts (representing 30 subjects) being evaluated cytologically. Fifty-eight of sixty breasts evaluated cytopathologically (97%) were reported as cytology Class I, and 2 of 60 (3%) were reported as cytology Class IIa. Cytopathological findings correlated well with mammogram and clinical breast exam results. No adverse events, including pain from the collection procedure, were reported. Conclusion: Based on this clinical study, we conclude that the Mammary Aspiration Specimen Cytology Test device is safe and effective for the collection of mammary aspirate specimens for laboratory cytopatho-logical testing.

基于ISO 9001标准的I期临床试验护理质量管理指标体系构建与应用

目的识别I期临床试验中护理质量问题与管理节点,构建基于ISO 9001标准的I期临床试验护理质量管理指标体系。方法通过文献回顾、头脑风暴、专家咨询等确定指标体系,并于2023年11月-2024年1月进行初步应用。结果建立了包含8个一级指标、54个二级指标的I期临床试验护理质量管理指标体系。应用后,I期临床试验的仪器设备使用规范性、数据录入规范性以及方案执行依从性均得以提高。结论基于ISO 9001标准的I期临床试验护理质量管理指标体系具有一定科学性和实用性,可用于临床试验护理质量管理。

Extract the Output Signal Characteristics of DC-DC Converter Based on Fourier Descriptor

The precondition of realizing feedback controlling DC DC converter to avoid chaotic state is to judge the behavior of the converter and take corresponding measures. In this paper, the output signals under different circuit parameters of the PWM buck converter have been analyzed. The method of using Fourier descriptor to extract output signals characteristics is put forward and proved to be a gist of identifying and classifying the behavior of DC DC converter. This method can establish a good foundation fo...

A Theoretical Evaluation of Optical Parametric Amplification in BBO Crystal

The noncollinear optical parametric amplification in BBO crystal is theoretically investigated. The phase matching angle, gain bandwidth, optimal noncollinear angle and conversion efficiency for both type-I and type-II BBO are simulated. The numerical simulation results are important to the practical optical parametric amplification experiments with BBO crystal.

On the Caginalp for a Conserve Phase-Field with a Polynomial Potentiel of Order 2<i>p</i>- 1

Our aim in this paper is to study on the Caginalp for a conserved phase-field with a polynomial potentiel of order 2p - 1. In this part, one treats the conservative version of the problem of generalized phase field. We consider a regular potential, more precisely a polynomial term of the order 2p - 1 with edge conditions of Dirichlet type. Existence and uniqueness are analyzed. More precisely, we precisely, we prove the existence and uniqueness of solutions.

浅谈I期临床试验受试者管理体会

探讨I期临床试验过程中受试者招募和受试者依从性的管理。分析招募的难点和提高招募效率的措施。在试验全过程中,研究人员扎实的医学知识技能和诚挚的关心、尊重、友善是提高受试者依从性的关键所在。

基于I/Q解调原理的校准方法及实验

同相/正交(In-phase/Quadrature,I/Q)解调技术广泛应用于射频信号相位控制系统。I/Q器件存在固有误差,如直流偏置、幅度不平衡、相位不平衡和电路长度不等。这些误差会导致输出的I/Q轨迹呈椭圆,相位为非线性,影响相位鉴别的精度。为减小误差带来的影响,提出一种基于I/Q解调技术的软件校准方法,并将此方法在自制基于贴片式芯片集成的I/Q解调印刷电路板上验证。测试表明,输出的I/Q信号经校准后相位误差≤±0.15°,幅度稳定度≤±1%,通道延时≤10 ns。此板卡设计和校准方法已在新升级的上海光源储存环高频束流丢失分析系统中的射频信号前端预处理中使用,各项指标均满足束流丢失分析系统中射频信号监测的要求。

数字化I/Q技术用于磁控管频率控制

采用磁控管做功率源的低能电子直线加速器在医疗、辐照、X射线检测等领域得到较为广泛的应用。磁控管产生的微波信号输入到加速管,对电子束进行加速,磁控管的工作频率稳定性对加速器电子束能量、能散及发射度产生直接的影响。但磁控管是一种振荡器,其频率受到温度、振动、负载牵引的影响会产生漂移,所以需要一套自动频率控制系统(Automatic Frequency Control,AFC)机构对磁控管进行频率控制。目前普遍采用的AFC机构主要是行波控相或双腔鉴频,对两路检波信号差分放大进而控制伺服电机进行调谐的方法实现磁控管的频率稳定。随着数字化I/Q和FPGA(Field-Programmable Gate Array)技术的不断发展,运用该技术进行磁控管的频率控制完全具备可行性。本文从理论和工程设计上阐述了数字化I/Q技术在磁控管频率控制上的应用。

LC/DAD/MSD技术研究大鼠服药胆汁中盐酸非洛普I相代谢产物

目的 研究大鼠服药后胆汁中盐酸非洛普 (DDPH)I相代谢物。方法 大鼠做胆管插管 ,分别收集ipDDPH之前的空白胆汁及服药后 12h内的服药胆汁 ,将大鼠胆汁以葡糖醛酸酶水解后进C 18SPE小柱进行纯化富集 ,再进行LC/DAD/MSD分析 ;同时将合成的 6个DDPH模拟代谢物M1-M6的对照品混合液按相同条件进行LC/DAD/MSD分析对照。结果 大鼠服药胆汁色谱图中峰A ,B ,C ,D ,E和F分别与M1,M2 ,M3,M5,M4 和M6的保留时间、紫外吸收光谱、分子量及碎片离子完全一致。结论 M1,M2 ,M3,M4 。

尿多酸肽注射液I期临床耐受性研究

目的 :观察人体对抗癌新药尿多酸肽注射液的耐受性、毒性反应及与剂量的关系 ,确定人体安全耐受剂量。方法 :采用改良的Fibonacci方法 ,从低剂量逐渐上升至高剂量 ,每剂量组至少 3例受试者 ,初始剂量为尿多酸肽注射液 10 0mL·d- 1 ,iv ,连用 5d ,如无明显毒性反应则进入下一剂量组 ,直至达到最大耐受量 (MTD)。根据爬坡结果推荐Ⅱ期临床用药剂量 ,再选 3例患者按其剂量 ,连用 4周 ,进行疗程耐受性试验。结果 :2 0例肿瘤患者进入试验 ,分别进行了 5个剂量组的研究。主要毒性反应为静脉炎 ,其次是轻度的胃肠道反应 ,MTD为 5 0 0mL·d- 1 。3例接受疗程耐受性试验患者 ,采用锁骨下静脉置管给药 ,无静脉炎出现 ,未观察到明显毒性反应。结论 :尿多酸肽注射液毒性反应轻 ,患者耐受性好。推荐Ⅱ期临床使用剂量及方法为 :30 0mL·d- 1 ,深静脉给药 ,连用 4周。