Prediction of Coefficient of Restitution for Impact Elastoplastic Spheres Considering Finite Plate Thickness

Collisions between objects are a relatively common phenomenon in nature.Analyses of collision processes can greatly contribute to solving problems such as impact-rub faults and particle impacts.The coefficient of restitution is a critical parameter in the analysis of collision processes.Many experiments have shown that the coefficient of restitution is closely related to the plate thickness,and the smaller the plate thickness,the more inaccurate the coefficient of restitution predicted by the existing model,which seriously affects the process of collision analysis.To remedy this shortcoming,this paper proposes a plate thickness influence factor with the ratio of sphere diameter to plate thickness as the variable.The plate thickness influence factor can optimize the coefficient of restitution model to effectively predict the coefficient of restitution of impacting elastoplastic spheres with finite plate thickness.Finally,the validity of the new model is verified using a large amount of experimental data.

中国国家药品监督管理局批准安罗替尼用于经两种系统化疗后疾病进展的晚期非小细胞肺癌的治疗

背景2018年5月8日,中国国家药品监督管理局(National Medical Products Administration,NMPA)批准了小分子多靶点抗血管抑制剂盐酸安罗替尼,用于既往经过至少两种系统化疗后疾病进展的晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的治疗。概要中国NMPA审查了一项随机双盲、安慰剂对照的III期临床试验,该临床试验的主要终点为总生存期(overall survival,OS)。试验共纳入437例患者随机分组(2∶1)接受安罗替尼(n=294)或安慰剂(n=143)治疗,每日1次,连服2周,停药1周。表皮生长因子受体(epidermal growth factor receptor,EGFR)基因敏感突变或间变性淋巴瘤激酶(activating anaplasticlymphomakinase,ALK)阳性的患者须经过NMPA已批准的药物治疗后出现疾病进展。安罗替尼为中国NMPA批准的用于治疗既往经过两种及以上系统化疗后疾病进展的晚期NSCLC患者的首个药物。安罗替尼组的中位OS(9.46个月)较安慰剂组[6.37个月;风险比(hazard ratio,HR)=0.70,95%置信区间(confidence Interval,CI):0.55–0.89;双侧log-rank P=0.002]显著延长。安罗替尼组的客观缓解率(objective responserate,ORR)为9.2%,安慰剂组为0.7%。安罗替尼组的中位缓解持续时间(durationofresponse,DoR)为4.83个月,95%CI为3.31–6.97个月。安罗替尼的常见不良反应(adverse drug reactions,ADRs)包括高血压(67.4%)、手足综合征(43.9%)、咳血(14.0%)、促甲状腺激素(thyroid stimulating hormone,TSH)升高(46.6%)、心电图QT间期(corrected QT Interval,QTc)延长(26.2%)。结论安罗替尼显著延长了患者的OS,可作为经二线及以上化疗后晚期或转移性非小细胞肺癌的一种新的治疗方案。

境外授权许可引进抗肿瘤新药临床研发策略的审评考虑

随着我国创新药产业的蓬勃发展,授权许可引进逐渐成为创新药企的重要研发模式。不同研发阶段引进的药物,在中国的研发策略有所不同。企业需全面整理药物已产生的境外临床数据,对临床药理学、安全性、有效性和种族敏感性进行详细的分析。应基于上述数据和分析的结果制定合理的临床研发策略。我们鼓励引进中国境内真正未满足临床需求的优质药物,尽可能在研发的早期阶段引进,以实现国内外的同步研发。新药引进后的临床研发策略对于药物能否顺利上市尤为重要,企业应遵循国家药品监督管理局已发布的指导原则和相应的临床指南进行临床试验设计,积极与监管部门进行沟通。

Clinical review considerations of class I PI3K inhibitors in hematolymphatic malignancies by Center for Drug Evaluation

Several phosphoinositide 3-kinase(PI3 K) inhibitors are currently approved to treat hematolymphatic malignant diseases worldwide, and many drugs that have the same target are in the clinical research stage. In March 2022,duvelisib became the first PI3 K inhibitor approved in China indicated for the treatment of hematolymphatic malignant diseases. Meanwhile, linperlisib and copanlisib have almost completed the technical review of the clinical specialty. The Center for Drug Evaluation(CDE) of the China National Medical Products Administration(NMPA) found that class I PI3 K inhibitors can cause various degrees of immune-related adverse events, which are associated with action mechanisms, affecting the benefit-risk assessment of the drugs. On April 21, 2021, the United States Food and Drug Administration(FDA) convened the Oncologic Drugs Advisory Committee(ODAC)meeting to discuss the safety of PI3 K inhibitors indicated for hematolymphatic malignancies and their related risk of death. The hematological tumor group of CDE of the China NMPA summarized and combined the data on PI3 K inhibitors listed or under technical review for marketing authorization applications and found that such products may have unique efficacy and safety characteristics in Chinese patients with malignant lymphoma.

Vibration harmonic suppression technology for electromagnetic vibrators based on an improved sensorless feedback control method

To realize low harmonic distortion of the vibration waveform output from electromagnetic vibrators,we propose a vibration harmonic suppression technology based on an improved sensorless feedback control method.Without changing the original driving circuit,the alternating current(AC)equivalent resistance of the driving coil is used to obtain high-precision vibration velocity information,and then a simple and reliable velocity feedback control system is established.Through the study of the effect of different values of key parameters on the system,we have achieved an effective expansion of the velocity characteristic frequency band of low-frequency vibration,resulting in an enhanced harmonic suppression capability of velocity feedback control.We present extensive experiments to prove the effectiveness of the proposed method and make comparisons with conventional control methods.In the frequency range of 0.01-1.00 Hz,without using any sensors,the method proposed in this study can reduce the harmonic distortion of the vibration waveform by about 40%compared to open-loop control and by about 20%compared to a conventional sensorless feedback control method.

Large-range displacement measurement in narrow space scenarios:fiber microprobe sensor with subnanometer accuracy

The embedded ultra-precision displacement measurement is of great interest in developing high-end equipment as well as precision metrology.However,conventional interferometers only focus on measurement accuracy neglecting the sensor volume and requirement of embedded measurement,thus hindering their broad applications.Here we present a new sensing method for realizing large-range displacement measurement in narrow space scenarios based on the combination of a fiber microprobe interference-sensing model and precision phase-generated carrier.This is achieved by microprobe tilted-axis Gaussian optical field diffraction and high-order carrier demodulation to realize large-range displacement sensing.It is uncovered that the microprobe element misalignment and phase demodulation means play pivotal roles in the interference signal and the accuracy of large-range displacement sensing.The analysis shows that the proposed interference-sensing method can effectively reduce the nonlinearities.Experimental results illustrate that the measurement range extends from 0 to 700 mm.Furthermore,the maximum nonlinear error is reduced from tens of nanometers to 0.82 nm over the full range,allowing subnanometer accuracy for embedded measurements in the hundreds of millimeters range.

Criteria and regulatory considerations for the conditional approval of innovative antitumor drugs in China:from the perspective of clinical reviewers

1 BACKGROUND Before the State Council of the People’s Republic of China issued the“Opinions on the Reform of the Examination and Approval System of Pharmaceutical and Medical Devices”[1],several problems existed in China’s drug evaluation and approval system.The long approval time and low efficiency of new drug marketing seriously affected the enthusiasm for drug innovation.To this end,the current“Drug Registration Regulation”(DRR)[2]was initiated by the National Medical Products Administration of China and officially implemented on July 1,2020.To encourage clinical value-oriented drug innovation,four expedited drug programs were first proposed,including breakthrough therapy drugs,conditional approval,priority review,and special approval procedures.For drugs listed in the expedited programs,the drug regulatory authorities and professional technical institutions should provide policy and technical support,prioritize the allocation of communication and review resources,and thereafter shorten the review time as much as possible.

China National Medical Products Administration approval summary:anlotinib for the treatment of advanced non-small cell lung cancer after two lines of chemotherapy

Background:On May 8,2018,the China National Medical Products Administration(NMPA)approved anlotinib,an orally administered anti-angiogenesis inhibitor,for the treatment of patients with advanced non-small cell lung can-cer(NSCLC)who have progressed after treatment with two or more lines of prior systemic chemotherapy.Main body of the abstract:China NMPA reviewed and inspected a regional double-blinded,placebo-controlled,Phase III trial comparing the overall survival(OS)of NSCLC patients between the anlotinib and placebo arms.A total of 437 patients were randomized(2:1)to receive either anlotinib(n=294)or placebo(n=143)once daily on a 2-week on and 1-week off schedule.Patients with epidermal growth factor receptor(EGFR)or activating anaplastic lymphoma kinase(ALK)genomic tumor aberrations should have disease progression on NMPA-approved therapy.Anlotinib is the first NMPA-approved drug for patients with advanced NSCLC who have progressed on at least two lines of prior systemic chemotherapies in China.The approval was based on a statistically and clinically significant improvement in median OS with anlotinib(9.46 months)compared with placebo[6.37 months;hazard ratio(HR])=0.70,95%confidence interval(CI)=0.55-0.89;two-sided log-rank P=0.002].The confirmed objective response rate(ORR)was 9.2%in the anlotinib arm and 0.7%in the placebo arm.The median duration of response(DoR)was 4.83 months,with a 95%CI of 3.31-6.97 months.The toxicity profile of anlotinib was consistent with that of known anti-angiogenesis inhibitors.Common adverse drug reactions(ADRs)in anlotinib-treated patients included hypertension(67.4%),hand-foot syndrome(43.9%),hemoptysis(14.0%),thyroid stimulating hormone(TSH)elevation(46.6%),and corrected QT interval(QTc)prolongation(26.2%).Short conclusion:Anlotinib demonstrated a clinically significant OS prolongation as a novel therapeutic option for advanced or metastatic NSCLC following at least two lines of chemotherapy.