优化解决肺癌患者在新型冠状病毒肺炎疫情期间诊疗问题及心理问题的探索

背景与目的随着新冠肺炎(novel coronavirus pneumonia,NCP)在全世界范围内的迅速蔓延及防控工作的升级,肺癌患者常规诊疗需求因疫情原因受到不同程度的限制,有必要了解肺癌患者在疫情期间诊疗需求及心理健康情况,为后续的诊疗提供合理化建议。方法采用电子问卷的形式,2020年3月4日7点发放,至3月6日7点截止,48 h收回368份问卷,覆盖了25个省自治区/直辖市。结果368例肺癌患者,18例未行抗肿瘤治疗,最终纳入分析的患者共350例。229例口服靶向治疗,化疗或免疫治疗治疗121例。41.3%静脉注射化疗或免疫治疗患者出现治疗中断,中断比例较口服靶向治疗高(21.0%)。无论是口服靶向治疗还是静脉化疗或免疫治疗,超过60%患者出现影像学检查延迟。近1/3患者出现新发症状或原有症状加重,26.6%-28.9%患者通过网络咨询后更改了治疗方案。40%-75%肺癌患者在NCP期间存在心理健康问题,95%以上的肺癌患者对国家采取疫情防控措施表示支持和有信心。结论在NCP期间,肺癌患者诊疗需求未得到满足,以化疗或免疫治疗的患者更明显,医疗机构恢复工作时应考虑优先解决。同时对患者存在的心理健康问题,应予以关注和疏解。

Sequential therapy according to distinct disease progression patterns in advanced ALK-positive non-small-cell lung cancer after crizotinib treatment

Objective: Crizotinib is recommended as the first-line therapy for advanced anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC). Despite its initial efficacy, patients ultimately acquire resistance to crizotinib within 1 year. In such patients, the optimal sequential therapy after crizotinib treatment remains unknown. This study explored which sequential therapy option confers the greatest benefit.Methods: A total of 138 patients with advanced ALK-positive NSCLC resistant to crizotinib were studied. Based on patterns of disease progression of metastases, patients were divided into 3 groups: brain progression, non-liver progression, and liver progression. Sequential therapies included crizotinib continuation plus local therapy, nextgeneration ALK inhibitors(ALKi's), and chemotherapy. The primary endpoint was overall survival(OS) from the time of crizotinib resistance to death or last follow-up.Results: The 138 patients included 64 cases with progression in brain, 57 cases in non-liver sites and 17 cases in liver. A significant difference in OS was observed among the distinct progression pattern(median OS, 25.4 months in brain, 15.8 months in non-liver, and 10.8 months in liver, respectively, P=0.020). The difference in OS among sequential therapies was statistically significant in the non-liver progression group(median OS, 27.6 months with next-generation ALKi's, 13.3 months with crizotinib continuation, and 10.8 months with chemotherapy,respectively, P=0.019). However, crizotinib continuation plus local therapy seems to provide non-inferior median OS compared with next-generation ALKi's for patients with brain progression(median OS, 28.9 months vs.32.8 months, P=0.204). And no significant differences in OS were found in patients with progression in liver(P=0.061).Conclusions: Crizotinib continuation together with local therapy might be a feasible strategy for patients with progression in brain beyond crizotinib resistance, as well as next-generation ALKi's. Next-generation ALKi's tended to provide a survival benefit in patients with non-liver progression.

Multi-walled carbon nanotubes conjugated to tumor protein enhance the uptake of tumor antigens by human dendritic cells in vitro

Anti-tumor immunotherapy is an important form of adjuvant cancer treatment [1, 2]. While chemotherapy encounters the obstacles of drug toxicity and resistance, immunotherapy usually has limited adverse effects, good patient tolerance, and the potential to significantly improve the prognosis [1-4]. Some clinical trials of im- munotherapy generated promising results in treating malignancies such as malignant melanoma, glioblastoma multiforme, or renal cell carcinoma, which tend to re- spond poorly to chemotherapies [3-5]. Dendritic cells (DC) play a crucial role in generating specific immune reaction to antigens, which generally need to be ingested, processed and presented by DC, before triggering B cell- or T cell- mediated responses. This core immune mechanism has been utilized in designing DC-based anticancer immunotherapy, whereby a patient's DC are expanded with in vitro culture,

Rapid and sensitive analysis of melatonin by LC-MS/MS and its application to pharmacokinetic study in dogs

A rapid and sensitive liquid chromatography tandem mass spectrometry method was established and validated for determination of melatonin in dog plasma using desvenlafaxine as an internal standard (IS). Plasma samples were pretreated by liquid–liquid extraction with ethyl acetate. Chromatographic separation was carried out on a C18 column at a flow rate of 0.2 ml/min by an isocratic mobile phase of methanol : 5 m M ammonium acetate : formic acid (40:60:0.1, v/v/v). Positive ion mode detection was performed using multiple reaction monitoring (MRM) at m/z 233.2→174.2 for melatonin and m/z 264.2→58.2 for desvenlafaxine.The method was linear in the concentration range of 0.020–10 ng/ml with a correlation coefficient ≥0.996. The intra-and inter-assay precision (%RSD) values were within 12.6% (LLOQ15.2%), and accuracy (%RE) ranged from -1.8% to 5.0% (LLOQ ±16.5%). The total analysis time was 3.0 min. The method was fully validated and successfully applied to a pharmacokinetic study of melatonin prolonged-release tablet in Beagle dogs. The values of half-life and Tmax were similar to the corresponding data reported before.

日粮系酸力在断奶仔猪上的应用研究进展

断奶仔猪因其胃肠道系统发育不完善,不能分泌足够的胃酸,加之一些饲料原料具有很强的酸结合力,使得仔猪胃内酸度较低,难以保证适宜的p H和足够的酶活性,容易导致仔猪出现消化不良和腹泻的现象。日粮系酸力是影响断奶仔猪胃内酸度的主要因素之一,适宜的日粮系酸力可以改善断奶仔猪的胃内酸度,维持体内消化、内分泌、微生态等系统的正常生理功能,同时能进一步改善仔猪的生产性能,降低其腹泻率。文章就断奶仔猪的日粮系酸力研究及其应用情况作一综述,以促进系酸力在断奶仔猪日粮配制上的合理应用。

Effect of propofol pretreatment on apoptosis in rat brain cortex after focal cerebral ischemia and reperfusion

The present study aimed to observe cortical expression of Bcl-2 and Bax,cysteine-dependent aspartate directed proteases-3 activity and apoptotic cell death in a rat model of middle cerebral artery occlusion pretreated with propofol.Results showed that,propofol pretreatment significantly reduced oxidative stress levels and attenuated neuronal apoptosis in the cortex of rats.Propofol pretreatment upregulated Bcl-2 expression,and downregulated Bax expression and cysteine-dependent aspartate directed proteases-3 activity.These findings indicate that propofol pretreatment inhibits cell apoptosis during focal cerebral ischemia/reperfusion injury.This neuroprotective effect is most likely achieved through the Bcl-2/Bax/cysteine-dependent aspartate directed proteases-3 pathway.

Variations in non-ST-elevation myocardial infarction care across three levels of hospitals in China:analysis from the China Acute Myocardial Infarction Registry

Objective To explore the variation of treatment and outcomes for NSTEMI across different-level hospitals, which potentially influenced by unbalanced economy and disparate medical care.Methods The China AMI registry consists of 108 hospitals across three levels (province, prefecture and county) throughout China.

基于图模型的决策谈判系统

本文研究的是基于矩阵形式的图模型决策谈判系统。冲突决策图模型法是一种集建模、分析和决策于一体的关于战略冲突的方法论。基于图模型法的决策支持系统是一个适用于解决谈判协商的实用分析工具。本文首次将图模型法和冲突分析决策系统运用到外交谈判,以人民币是否升值为背景,将图模型理论运用于中美双方政府及经济学家之间的谈判,并为此提供战略决策建议。

The optimal timing for delayed percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction presenting beyond 12 hours after symptoms onset

Objective To evaluate the impact of the timing of delayed PCI on the outcomes of patients with STEMI missing out on early reperfusion therapy within 12 h after symptom onset and ascertain the eligible time window to perform delayed PCI.Methods Among 28,061 patients registered in China Acute Myocardial Infarction(CAMI)registry,a total of 3,048 stable patients with STEMI who did not underwent any early reperfusion therapy within 12 hours after symptom onset and received delayed PCI at recovery stage were finally enrolled.

The decision-making of treatment and outcome in elderly Chinese patients with severe aortic stenosis

Objective There is a consensus that intervention should be advised in patients with severe,symptomatic aortic stenosis(AS).Decision to operate raises specific problems in the elderly because of the increasing operative comorbidity and mortality.However,little is known regarding the proportion of Chinese patients who denied to receive intervention and the reasons leading to the denial.This study is designed to analyze factors associated with decision-making and prognosis in elderly patients with severe,symptomatic AS.

Rapid and sensitive analysis of cyclobenzaprine by LCeMS/MS:Application to a pharmacokinetic study of cyclobenzaprine in dog

A rapid and sensitive liquid chromatographyetandem mass spectrometry method was developed and validated for the quantification of cyclobenzaprine in dog plasma.After extracted with organic solvent,post-treatment samples were separated on an Agela C18 column interfaced with a triple quadrupole tandem mass spectrometer in positive electrospray ionization mode.Multiple reaction monitoring was performed using the transitions of m/z 276.2/216.1 and m/z 325.1/109.0 to quantify cyclobenzaprine and escitalopram(internal standard),respectively.The mobile phase consisted of acetonitrile:5 mM ammonium acetate:formic acid(90:10:0.01,v/v/v)at a flow rate of 0.3 ml/min.The total analysis time was 2.4 min.The method was linear over the concentration range of 0.0200e10.0 ng/ml.The intra-and inter-day precision was within 12.8%in terms of relative standard deviation(RSD%)and the accuracy within 5.6%in terms of relative error.This method was successfully applied in a pharmacokinetic study of extended-release cyclobenzaprine in dogs.

Quantitative determination of isradipine in dog plasma by an ultra performance liquid chromatographyetandem mass spectrometry method

A simple,sensitive and specific ultra performance liquid chromatographyetandem mass spectrometry(UPLCeMS/MS)method was developed for the analysis of isradipine in dog plasma.After extracted with organic solvent,dog plasma samples were analyzed on an Acquity UPLC BEH C18 column interfaced with a triple quadrupole tandem mass spectrometer in positive electrospray ionization mode.Acetonitrile:water:formic acid(80:20:0.3,v/v/v)was used as the mobile phase at a flow rate of 0.2 ml/min.The chromatographic run time of each sample was 1.4 min.The calibration curve in plasma was linear in the range of 0.1e40.0 ng/ml.The intra-and inter-day precision was within 13.5%in terms of relative standard deviation(RSD%)and the accuracy was required to be 96.5%e98.4%.The validated UPLCeMS/MS method was successfully applied in a pharmacokinetic study of controlledrelease isradipine in dogs.

Evidence-based Care for Rehabilitation Nursing Effect of Patients with Patellar Fracture

Objective.To analyze the effect of applying evidence-based care in rehabilitation nursing effect of patients with patellar fractures.Methods.A total of 54 patients with patellar fractures were randomly selected from the hospital.The diagnosis and treatment time were from the beginning of July 2018 to end of June 2019.The digital table grouping was adopted to divide patients into two groups with each group consists of 27 patients with this disease.Both groups underwent routine nursing and the experimental group with increased evidence-based care.Results.Compared with the control group,the knee function evaluation,complications and nursing satisfaction of the experimental group were more ideal,and the difference was statistically significant(P<0.05).Conclusion.Evidence-based care in rehabilitation nursing of patients with patellar fracture can obtain ideal nursing effect.

Donggan Speech Recognition Based on Convolution Neural Networks

Donggan language, which is a special variant of Mandarin, is used by Donggan people in Central Asia. Donggan language includes Gansu dialect and Shaanxi dialect. This paper proposes a convolutional neural network (CNN) based Donggan language speech recognition method for the Donggan Shaanxi dialect. A text corpus and a pronunciation dictionary were designed for of Donggan Shannxi dialect and the corresponding speech corpus was recorded. Then the acoustic models of Donggan Shaanxi dialect was trained by CNN. Experimental results demonstrate that the recognition rate of proposed CNNbased method achieves lower word error rate than that of the monophonic hidden Markov model (HMM) based method, triphone HMM-based method and DNN- based method.

Tenecteplase versus alteplase in treatment of acute ST-segment elevation myocardial infarction:A randomized non-inferiority trial

Background:A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator(rhTNK-tPA)has previously shown its preliminary efficacy in ST elevation myocardial infarction(STEMI)patients.This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase(rt-PA)in Chinese patients with STEMI.Methods:In this multicenter,randomized,open-label,non-inferiority trial,patients with acute STEMI were randomly assigned(1:1)to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min.The primary endpoint was recanalization defined by thrombolysis in myocardial infarction(TIMI)flow grade 2 or 3.The secondary endpoint was clinically justified recanalization.Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events(MACCEs)and safety endpoints.Results:From July 2016 to September 2019,767 eligible patients were randomly assigned to receive rhTNK-tPA(n=384)or rt-PA(n=383).Among them,369 patients had coronary angiography data on TIMI flow,and 711 patients had data on clinically justified recanalization.Both used a–15%difference as the non-inferiority efficacy margin.In comparison to rt-PA,both the proportion of patients with TIMI grade 2 or 3 flow(78.3%[148/189]vs.81.7%[147/180];differences:–3.4%;95%confidence interval[CI]:–11.5%,4.8%)and clinically justified recanalization(85.4%[305/357]vs.85.9%[304/354];difference:–0.5%;95%CI:–5.6%,4.7%)in the rhTNK-tPA group were non-inferior.The occurrence of 30-day MACCEs(10.2%[39/384]vs.11.0%[42/383];hazard ratio:0.96;95%CI:0.61,1.50)did not differ significantly between groups.No safety outcomes significantly differed between groups.Conclusion:rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery,a validated surrogate of clinical outcomes,among Chinese patients with acute STEMI.Trial registration:www.ClinicalTrials.gov(No.NCT02835534).

Distributed dynamic task allocation for unmanned aerial vehicle swarm systems:A networked evolutionary game-theoretic approach

Task allocation is a key aspect of Unmanned Aerial Vehicle(UAV)swarm collaborative operations.With an continuous increase of UAVs’scale and the complexity and uncertainty of tasks,existing methods have poor performance in computing efficiency,robustness,and realtime allocation,and there is a lack of theoretical analysis on the convergence and optimality of the solution.This paper presents a novel intelligent framework for distributed decision-making based on the evolutionary game theory to address task allocation for a UAV swarm system in uncertain scenarios.A task allocation model is designed with the local utility of an individual and the global utility of the system.Then,the paper analytically derives a potential function in the networked evolutionary potential game and proves that the optimal solution of the task allocation problem is a pure strategy Nash equilibrium of a finite strategy game.Additionally,a PayOff-based Time-Variant Log-linear Learning Algorithm(POTVLLA)is proposed,which includes a novel learning strategy based on payoffs for an individual and a time-dependent Boltzmann parameter.The former aims to reduce the system’s computational burden and enhance the individual’s effectiveness,while the latter can ensure that the POTVLLA converges to the optimal Nash equilibrium with a probability of one.Numerical simulation results show that the approach is optimal,robust,scalable,and fast adaptable to environmental changes,even in some realistic situations where some UAVs or tasks are likely to be lost and increased,further validating the effectiveness and superiority of the proposed framework and algorithm.

Prognostic value of calcium and phosphorus status in elderly heart disease patients with tricuspid regurgitation

To the Editor:Tricuspid regurgitation(TR)associated with valve disease is a general medical issue with growing prevalence and socioeconomic burden.TR,especially moderate or severe TR,has been reported to be associated with an increased risk of heart failure and mortality.^([1])Studies have shown that blood calcium levels and blood phosphorus levels have a great influence on the human body,especially on the cardiovascular system.Elevated serum calcium levels were reported to be a risk factor for cardiovascular disease.^([2])A meta-analysis reported that moderate dietary calcium intake protects against cardiovascular and all-cause mortality and that calcium supplementation reduces mortality in women.^([3])

纳米酶

纳米酶(Nanozymes)是由我国科学家首次提出的新概念,它是一类具有生物催化功能的纳米材料,能够基于特定的纳米结构催化天然酶的底物并作为酶的代替品。自2007年首次报道以来,全球已有来自于55个国家的420多个研究机构证实了纳米酶的普遍规律。纳米酶的发现第一次揭示纳米材料蕴含一种独特的纳米效应———类酶催化效应。纳米酶作为一种新材料,既有纳米材料本身的理化性质,又有类似酶的催化功能,兼具天然酶与人工酶的优势于一身。其中,纳米结构不仅赋予纳米酶高效催化功能,而且使纳米酶比天然酶稳定,易于规模化生产。另外,纳米酶独特的多酶活性将为设计廉价、稳定、各种各样全新的催化级联反应提供功能分子。纳米酶是多学科交叉融合的典范,2022年被IUPAC评为十大化学新兴技术。在全球从事化学、酶学、材料学、生物学、医学、理论计算等多领域科学家的共同推进下,如今纳米酶已经成为新的研究热点。我国科学家在这一新兴领域一直发挥着引领作用,解析了纳米酶的构⁃效关系,将其催化活性提高了约1万倍,实现了超越天然酶的理性设计,创造了全球首个纳米酶产品,出版了纳米酶学英文专著,发布纳米酶术语及中国/国际标准化。更可喜的是,纳米酶新领域汇集了一大批多学科交叉融合的优秀青年科学家,推动纳米酶进入高速发展阶段,纳米酶的种类已经超过1200多种,其催化机制研究也更加深入,应用研究也从当初的检测逐步拓展到纳米酶催化医学、传感检测、绿色合成、新能源、环境治理等多个领域。本文向读者介绍纳米酶自发现以来的主要进展,包括最近发现的天然纳米酶,期待纳米酶从新概念、新材料衍生出新技术、新产品、新商品,服务人类健康,并带动新学科发展。

随机参考价格影响下带成本约束的库存系统

本文深入探讨了制造商在考虑随机参考价格效应的情况下,对生产和定价做出最佳决策的问题。我们将其表述为随机控制问题,目的是在成本约束下最大化净利润函数。首先,为了解决约束优化问题,我们可以利用拉格朗日乘子方法将其转换为无约束问题。通过动态规划方法和粘性解方法,本文研究结果揭示了无约束问题的值函数是汉密尔顿–雅可比–贝尔曼(HJB)方程的唯一粘性解。然而,HJB方程难以得到显式解,我们利用有限差分理论和随机递归算法建立了合适的数值近似方案。我们证明了HJB方程的有限差分方案的收敛性,并证明了该方案的解收敛于HJB方程的解。此外,我们通过确定适当的拉格朗日乘子,在约束问题的最优解和无约束问题的最优解之间建立联系。最后,我们进行了数值实验并分析了关键参数的灵敏度。我们的实验结果可以为制造商提供库存和定价的参考。