RVD方案对新诊断多发性骨髓瘤患者缓解深度的研究

目的:分析来那度胺、硼替佐米及地塞米松(lenalidomide,bortezomib and dexamethasone,RVD)方案治疗新诊断多发性骨髓瘤(newly diagnosed multiple myeloma,NDMM)患者的疗效和安全性.方法:回顾性分析2015年1月至2019年5月首都医科大学附属北京朝阳医院收治的48例NDMM患者,统计其临床特征及治疗疗效.结果:48例患者的中位年龄为59(34~79)岁,Durie-Salmon分期Ⅲ期患者44例;ISS分期Ⅱ期患者15例,Ⅲ期患者19例,12例伴浆细胞瘤,细胞遗传学高危患者占32.5%.全部患者接受RVD方案化疗,中位4(1~9)个周期,总有效率97.9%,完全缓解(complete response,CR)率为35.4%,4个周期较2个周期化疗后非常好的部分缓解(very good partial response,VGPR)以上疗效提高为(84.6% vs. 64.1%);平均采集CD34+细胞数4.2(±2.6)×106/kg;诱导治疗后下一代流式微小残留病变(minimal residual disease,MRD)阴性率为20.6%,其中2例移植前MRD阳性者在移植后MRD转阴.治疗过程中2例发生3~4级血液学毒性,未发生3级以上非血液学不良事件.结论:采用RVD方案治疗NDMM患者4个疗程,缓解率高,不良反应可耐受,且不影响干细胞采集.RVD诱导联合自体造血干细胞移植可进一步提高MRD阴性率.

Hybrid customer requirements rating method for customer-oriented product design using QFD

Quality function deployment （QFD） is a well-known customer-oriented product design methodology. Rating the final importance of customer requirements （CRs） is really a very es- sential starting point in the implementation of QFD, since it largely affects the target setting value of design requirements. This pa- per aims to propose a novel method to deal with the relative importance ratings （RIRs） of CRs problem considering customers＇ diversified requirements and unknown information on customers＇ weights, which is an indispensable process for determining the final importance ratings of CRs. First, a new concept of customer＇s assessment structure is proposed according to the basic idea of grey relational analysis （GRA）, and then a constrained nonlinear optimization model is constructed to describe the assessment information aggregation factors of CRs considering customers＇ personalized and diversified requirements. Furthermore, an im- mune particle swarm optimization （IPSO） algorithm is designed to solve the model, and the weight vector of customers is obtained. Finally, a car door design example is introduced to illustrate the novel hybrid GRA-IPSO method＇s potential application in deter- mining the RIRs of CRs.

Load Balancing Routing Algorithm Based on Extended Link States in LEO Constellation Network

As an important part of satellite communication network,LEO satellite constellation network is one of the hot research directions.Since the nonuniform distribution of terrestrial services may cause inter-satellite link congestion,improving network load balancing performance has become one of the key issues that need to be solved for routing algorithms in LEO network.Therefore,by expanding the range of available paths and combining the congestion avoidance mechanism,a load balancing routing algorithm based on extended link states in LEO constellation network is proposed.Simulation results show that the algorithm achieves a balanced distribution of traffic load,reduces link congestion and packet loss rate,and improves throughput of LEO satellite network.

The pathology of urinary bladder lesions with an inverted growth pattern

Inverted lesions in the urinary bladder have been the source of some difficulty in urological pathology. The two common ones are von Brunn＇s nests and cystitis cystic/cystitis glandularis, which are considered normal variants of urothelium. Apart from them, a number of other rare urothelial lesions with inverted growth pattern occur in the urinary bladder. Some of them are only reactive conditions, just as pseudocarcinomatous hyperplasia. Some are benign tumors, namely inverted papilloma. Whereas others are malignant neoplasms, including inverted papillary urothelial neoplasm of low malignant potential （PUNLMP）, non-invasive inverted papillary urothelial carcinoma （low-grade and high-grade）, and invasive urothelial carcinoma （inverted, nested and big nested variants）. Because of the overlapping morphological features of all the inverted lesions mentioned above, even between high-grade invasive carcinoma and psendoearcinomatous hyperplasia which are only a kind of reactive conditions, it is very important for the surgical pathologist to recognize and be familiar with these inverted lesions in urinary bladder. In this article, we review these spectrums of inverted lesions of the urinary bladder. Emphasis is placed on histogenesis, morphology, differential diagnosis of these lesions, and the pathologic grading of the non-invasive inverted neoplasms, such as inverted papilloma, inverted PUNLMP, non-invasive inverted papillary urothelial carcinoma with low-grade, and non-invasive inverted papillary urothelial carcinoma with high-grade.

Scheduling optimization of task allocation in integrated manufacturing system based on task decomposition

How to deal with the collaboration between task decomposition and task scheduling is the key problem of the integrated manufacturing system for complex products. With the development of manufacturing technology, we can probe a new way to solve this problem. Firstly, a new method for task granularity quantitative analysis is put forward, which can precisely evaluate the task granularity of complex product cooperation workflow in the integrated manufacturing system, on the above basis; this method is used to guide the coarse-grained task decomposition and recombine the subtasks with low cohesion coefficient. Then, a multi-objective optimieation model and an algorithm are set up for the scheduling optimization of task scheduling. Finally, the application feasibility of the model and algorithm is ultimately validated through an application case study.

Local-State Routing in Satellite Constellation Networks from the Perspective of Complex Network

Routing algorithms in satellite constellation networks usually make use of the local state information to adapt to the topology and traffic dynamics,since it’s difficult to obtain the global states in time due to the spatial large-scale feature of constellation networks.Furthermore,they use different range of local states and give these states distinct weights.However,the behind design criterion is ambiguous and often based on experience.This paper discusses the problem from the perspective of complex network.A universal local-state routing model with tunable parameters is presented to generalize the common characteristics of local-state routing algorithms for satellite constellation networks.Based on this,the impacts of localstate routing algorithms on performance and the correlation between routing and traffic dynamics are analyzed in detail.Among them,the tunable parameters,the congestion propagation process,the critical packet sending rate,and the network robustness are discussed respectively.Experimental results show that routing algorithms can achieve a satisfactory performance by maintaining a limited state awareness capability and obtaining the states in a range below the average path length.This provides a valuable design basis for routing algorithms in satellite constellation networks.

Phenylalanine deprivation inhibits multiple myeloma progression by perturbing endoplasmic reticulum homeostasis

Amino acid metabolic remodeling is a hallmark of cancer,driving an increased nutritional demand for amino acids.Amino acids are pivotal for energetic regulation,biosynthetic support,and homeostatic maintenance to stimulate cancer progression.However,the role of phenylalanine in multiple myeloma(MM)remains unknown.Here,we demonstrate that phenylalanine levels in MM patients are decreased in plasma but elevated in bone marrow(BM)cells.After the treatment,phenylalanine levels increase in plasma and decrease in BM.This suggests that changes in phenylalanine have diagnostic value and that phenylalanine in the BM microenvironment is an essential source of nutrients for MM progression.The requirement for phenylalanine by MM cells exhibits a similar pattern.Inhibiting phenylalanine utilization suppresses MM cell growth and provides a synergistic effect with Bortezomib(BTZ)treatment in vitro and murine models.Mechanistically,phenylalanine deprivation induces excessive endoplasmic reticulum stress and leads to MM cell apoptosis through the ATF3eCHOPeDR5 pathway.Interference with ATF3 significantly affects phenylalanine deprivation therapy.In conclusion,we have identified phenylalanine metabolism as a characteristic feature of MM metabolic remodeling.Phenylalanine is necessary for MM proliferation,and its aberrant demand highlights the importance of lowphenylalanine diets as an adjuvant treatment for MM.

Expert consensus on the diagnosis and treatment of solid tumors with BRAF mutations

The BRAF gene is an important signaling molecule in human cells that is involved in the regulation of cell growth,differentiation,and survival.When the BRAF gene mutates,it can lead to abnormal activation of the signaling pathway,which promotes cell proliferation,inhibits cell apoptosis,and ultimately contributes to the occurrence and development of cancer.BRAF mutations are widely present in various cancers,including malignant melanoma,thyroid cancer,colorectal cancer,non-small cell lung cancer,and hairy cell leukemia,among others.BRAF is an important target for the treatment of various solid tumors,and targeted combination therapies,represented by BRAF inhibitors,have become one of the main treatment modalities for a variety of BRAF-mutation-positive solid tumors.

Boosting self-trapped exciton emission from Cs_(3)Cu_(2)I_(5)nanocrystals by doping-enhanced exciton-phonon coupling

Self-trapped excitons(STEs)emission from halide perovskites with strong exciton-phonon coupling has attracted considerable attention due to the widespread application in optoelectronic devices.Nevertheless,the in-depth understanding of the relationship between exciton-phonon coupling and luminescence intensity remains incomplete.Herein,a doping-enhanced exciton-phonon coupling effect is observed in Cs_(3)Cu_(2)I_(5)nanocrystals(NCs),which leads to a remarkable increasement of their STEs emission efficiency.Mechanism study shows that the hetero-valent substitution of Cu+with alkaline-earth metal ions(AE^(2+))causes a greater degree of Jahn-Teller distortion between the ground state and excited state structures of[Cu_(2)I_(5)]_(3)-clusters as evidenced by our spectral analysis and first-principles calculations.As a consequence,an X-ray detector based on these Cs_(3)Cu_(2)I_(5):AE NCs delivers an X-ray imaging resolution of up to 10 lp·mm^(-1) and a low detection limit of 0.37μGyair·s^(-1),disclosing the potential of doping-enhanced exciton-phonon coupling effect in improving STEs-emission and practical application for X-ray imaging.

A supplier evaluation model based on customer demand in blockchain tracing anti-counterfeiting platform project management

This study assesses supplier selection at the beginning of project management to establish an evaluation system corresponding to blockchain tracing anti-counterfeiting platforms(BTAP).First,this paper determines 20 evaluation criteria from the four dimensions of platform overview,core technology,application support,and operations management.On this basis,multi-criteria decision making(MCDM)based on customer needs is proposed,which consists of three main steps.First,quality function deployment(QFD)and the best and worst method(BWM)are used to evaluate the four dimensions of the BTAP and specific evaluation criteria from the perspective of customers to obtain the criteria weight.Then,this method uses the extended Vlse Kriterjumska Optimizacija I Kompromisno Resenje(VIKOR)approach to sort the alternatives.Finally,the improved decision making trial and evaluation laboratory(DEMATEL)method is used to analyse the relationships between the 20 criteria in the four dimensions.The feasibility and effectiveness of this method are verified by an example.According to the sensitivity analysis and comparative analysis,the results show that this method can evaluate blockchain anti-counterfeiting enterprises.The main conclusions are as follows:the core technology is the most impor-tant factor influencing the choice of a BTAP project,and the role of application support in evaluation cannot be ignored.

Research Article Acetic acid-mediated rapid cubic-to-hexagonal(α-β)phase transformation for ultra-bright lanthanide-dopedβ-NaYF_(4)nanobioprobes

Hexagonal-phase NaYF_(4)(β-NaYF_(4))has been acknowledged to be one of the most efficient doping hosts to prepare bright lanthanide-doped luminescent nano-bioprobes for various biomedical applications.However,to date,it remains a great challenge to synthesize ultra-bright lanthanide-dopedβ-NaYF_(4)nano-bioprobes under a low reaction temperature by using conventional synthetic methods.Herein,we first develop an acetic acid(HAc)-mediated coprecipitation method for the preparation of ultrabright lanthanide-dopedβ-NaYF_(4)nanoprobes under a low reaction temperature at 200℃.Based on a series of comparative spectroscopic investigations,we show that the use of HAc in the reaction environment can not only promote the rapidα-βphase transformation of NaYF_(4)host at 200℃ within 1 h but also boost the absolute photoluminescence quantum yield(PLQY)of NaYF_(4)nanocrystals to 30.68%for near-infrared emission and to 3.79%for upconversion luminescence,both of which are amongst the highest values for diverse lanthanide-doped luminescent nanocrystals ever reported.By virtue of their superior nearinfrared luminescence,we achieve optical-guided dynamic vasculature imaging in vivo of the whole body at a high spatial resolution(23.8μm)under 980 nm excitation,indicating its potential for the diagnosis and treatment evaluation of vasculaturerelated diseases.

Structure basis for allosteric regulation of lymphocytic choriomeningitis virus polymerase function by Z matrix protein

DearEditor,The Arenaviridae family(recently assigned to the Bunyavirales order)is a group of emerging viruses that include causative agents of severe hemorrhagic fevers with high mortality in humans(de la Torre,2009).Lymphocytic choriomeningitis virus(LCMV)is the prototypic member of the Arenaviridae family and belongs to the Old World(OW)arenavirus together with Lassa virus(LASV),which are distinct from the New World(NW)arenavirus[e.g.Machupo virus(MACV)and Junin virus(JUNV)].LCMV infection in the fetus and newborm results in severe impairment of brain development associated with sensory loss and mental retardation and is also known to be associated with severe systemic infection with high mortality in transplantation patients(Palacios et al.,2008).

Transthoracic Salus Valve Feasibility Study: Short-Term Outcomes of a Transcatheter Self-Expandable Pulmonary Valve

Objective:The size and morphology of the right ventricular outflow tract(RVOT)in patients suffering from long-term pulmonary regurgitation(PR)after native RVOT(NRVOT)reconstruction are important factors affecting the feasibility,safety,and effectiveness of transcatheter pulmonary valve replacement.The purpose of this study was to evaluate the feasibility,safety,and effectiveness of a transthoracic Salus valve(Balance Medical Technology Co.,Ltd,Beijing,China)in patients with moderate-to-severe PR after NRVOT reconstruction.Methods:Patients with moderate-to-severe PR after NRVOT reconstruction were selected between June 2021 and November 2021 at Beijing Anzhen Hospital.Demographic data as well as preoperative,intraoperative,and follow-up data were reviewed.Results:Ten patients with moderate-to-severe PR after NRVOT reconstruction underwent physical examination,transthoracic echocardiography,and cardiovascular magnetic resonance imaging.Seven patients were selected for transthoracic Salus valve replacement.Six patients underwent implantation of the Salus valve successfully.One valve migrated and was embolized during recovery of the delivery device;the Salus valve was surgically explanted and sutured to the inner wall of the main pulmonary artery.At a mean follow-up of(5.5±1.1)months,dysfunction or migration of the Salus valve embolism was not observed.Conclusions:This early feasibility study demonstrates the feasibility,safety,and effectiveness of transthoracic implantation of a Salus valve in patients with moderate-to-severe PR after NRVOT reconstruction.The short-term effectiveness is clear,medium and long-term effectiveness requires longer follow-up.

Differential pricing and production strategies for heterogeneous products under cannibalization and promotional effects

This study examines the optimal pricing and production strategy of a closed-loop supply chain consisting of a manufacturer, a recycler, and consumers. Considering the cannibalization and promotion effects of remanufactured products on new and secondhand products, we constructed Stackelberg game models under different scenarios. We analyze the impact of the changes in the two effects on the optimal prices and production strategies of the manufacturer and recycler, as well as their countermeasures. We find that (i) how the cannibalization and promotional effects influence the manufacturer and the recycler's pricing and production strategies differ under different scenarios;(ii) when the two effects exceed a threshold, the manufacturer abandons new or remanufactured products, and the recycler prefers to stop production on its new products or continue to remanufacture products;and (iii) the two effects always reduce the profits of the manufacturer and increase the profits of the recycler.