Prognostic value of programmed death.1, programmed death-ligand 1, programmed death-ligand 2 expression, and CD8(+) T cell density in primary tumors and metastatic lymph nodes from patients with stage T1.4N+M0 gastric adenocarcinoma

Background: Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1) immunotherapy has been proved to be effective on gastric cancer in ongoing clinical trials. However, the value of PD-L1 in predicting responses of patients with gastric cancer to anti-PD-1/PD-L1 immunotherapy is controversial. Some studies suggested that intra-and inter-tumoral heterogeneity of PD-L1 expression might explain the controversy.This study aimed to analyze the expression of PD-L1, PD-L2, and PD-1 as well as CD8(+) T-cell density in primary tumors and lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma to explore the heterogeneity of PD-1 signaling pathway molecules.Methods: In primary tumors and metastatic as well as non-metastatic lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma, we detected PD-L1 and PD-L2 expression with immunohistochemistry. CD8(+)T-cell density in primary tumors and PD-1 expression on CD8(+)T cells were detected with immunofluorescence. Univariate analysis was used to determine the prognostic values of them. Cox proportional hazard regression model was used to identify independent risk factors that affect patients' overall survival and disease-free survival.Results: Among 119 eligible patients who had undergone surgical resection, the positive rate of PD-L1 was higher in metastatic lymph nodes than in primary tumors(45.4% vs. 38.7%, P = 0.005); the positive rate of PD-1 on CD8(+)T cells was significantly higher in primary tumors and metastatic lymph nodes than in tumor-free lymph nodes(both P < 0.001). The intensity of PD-1 expression on CD8(+) T cells in primary tumors and in metastatic lymph nodes were stronger than that in tumor-free lymph nodes from the same patient. Beside, the positive rate of PD-L2 did not show any differences between primary tumors and metastatic lymph nodes. In multivariate analysis, PD-L1 expression,PD-L2 expression, a low density of CD8(+) T cells in primary tumors, and PD-1 expression on CD8(+) T cells in primary tumors were associated with poor prognosis.Conclusion: The expression of PD-L1 is heterogeneous in primary tumors and in metastatic lymph nodes from patients with stageT1-4 N+M0 gastric adenocarcinoma, which might explain the inconsistent results in assessing the prognostic value of PD-L1 expression in previous studies.

Current management of chemotherapy-induced neutropenia in adults:key points and new challenges

Chemotherapy-induced neutropenia(CIN)is a potentially fatal and common complication in myelosuppressive chemotherapy.The timing and grade of CIN may play prognostic and predictive roles in cancer therapy.CIN is associated with older age,poor functional and nutritional status,the presence of significant comorbidities,the type of cancer,previous chemotherapy cycles,the stage of the disease,specific chemotherapy regimens,and combined therapies.There are many key points and new challenges in the management of CIN in adults including:(1)Genetic risk factors to evaluate the patient’s risk for CIN remain unclear.However,these risk factors urgently need to be identified.(2)Febrile neutropenia(FN)remains one of the most common reasons for oncological emergency.No consensus nomogram for FN risk assessment has been established.(3)Different assessment tools[e.g.,Multinational Association for Supportive Care in Cancer(MASCC),the Clinical Index of Stable Febrile Neutropenia(CISNE)score model,and other tools]have been suggested to help stratify the risk of complications in patients with FN.However,current tools have limitations.The CISNE score model is useful to support decision-making,especially for patients with stable FN.(4)There are still some challenges,including the benefits of granulocyte colony stimulating factor treatment and the optimal antibiotic regimen in emergency management of FN.In view of the current reports,our group discusses the key points,new challenges,and management of CIN.

Multi-criteria group decision making with fuzzy data:an extension of the VIKOR method

The VIKOR method is a multi-criteria decision making aid, which employs linear normalization to offer compromise solu- tions and has been successfully applied to various group decision making problems. However, the conventional VIKOR techniques used to integrate group judgments and the information loss arising from defuzzification are problematic and distort final outcomes. An improved integration method, which is optimization-based, is proposed. And it can handle fuzzy criteria values and weights. The precondition for accurately defuzzifying triangular fuzzy num- bers is identified. Several effective defuzzification procedures are proposed to improve the extant VIKOR, and a comprehensive evaluation framework is offered to aid multi-criteria group decision making. Finally, a numerical example is provided to illustrate the practicability of the proposed method.

Anti-tumor activities and apoptotic mechanism of ribosome-inactivating proteins

Ribosome-inactivating proteins(RIPs) belong to a family of enzymes that attack eukaryotic ribosomes and potently inhibit cellular protein synthesis.RIPs possess several biomedical properties,including anti-viral and anti-tumor activities.Multiple RIPs are known to inhibit tumor cell proliferation through inducing apoptosis in a variety of cancers,such as breast cancer,leukemia/lymphoma,and hepatoma.This review focuses on the anti-tumor activities of RIPs and their apoptotic effects through three closely related pathways:mitochondrial,death receptor,and endoplasmic reticulum pathways.

New method for hybrid multiple attribute decision-making problems with decision maker's aspiration level

How can we account for decision maker's aspiration level in multiple attribute decision-making problems? This is a question that has recently gained much scholarly attention. This study draws on the prospect theory and the Dempster-Shafer theory to propose a method that can resolve this issue. First, the precise and interval numbers and linguistic labels are compared, and then, the decision matrix is transformed into a prospect decision matrix on the basis of decision maker's aspiration level. Second, the Dempster-Shafer theory is applied to aggregate the prospect values of all alternatives on each attribute using their prospect belief intervals. Third, the orders of alternatives are obtained for all decision methods by comparing prospect belief intervals. Final, the effectiveness and feasibility of the proposed method are demonstrated by using an illustrative example. © 1990-2011 Beijing Institute of Aerospace Information.

Preliminary outcome of rituximab-containing salvage regimens on relapsed or refractory B-cell non-Hodgkin’s lymphoma: single institution experience

Objective： The prognosis of relapsed or refractory B-cell lymphoma is poor, with a short-term survival after conventional second-line chemotherapy, Rituximab, a chimeric anti-CD20 antigen, in combination with CHOP or CHOP-like chemotherapy may improve both disease free survival （DFS） and overall survival （OS） of naive patients, but its role in the second-line therapy for relapsed non-Hodgkin＇s Lymphoma （NHL） remains to be defined, This study aimed to evaluate the efficacy of rituximab-containing salvage regimens for relapsed or refractory NHL, and observe the toxicities. Methods： The clinical data of 54 patients, who were with relapsed or refractory NHL and treated in the Cancer Center of Sun Yat-sen University, were analyzed retrospectively, Of the 54 patients, 29 were man, 25 were women, with a median age of 52.5 years old （range 18 to 75）; 50 patients （92.6%） scored 0-1 for the ECOG performance status; for second-line international prognostic index （slPI）, 21 （38.9%） scored 0-1,30 （55.6%） scored 2 to 3, and 3 （5.6%） scored 4-5; 40 cases were diffuse large B-cell lymphoma （DLBCL）, accounting for 74.1% of all subtypes, Rituximab was administered intravenously at a dose of 375 mg/m^2 at the day before each chemotherapy cycle, The second or third-line salvage regimens included EPOCH, CHOP, DHAP, DICE, IVAC, IMVP-16 and FND, Results： Of the 54 patients, 49 received retuximab-containing salvage regimens, The objective response rate of the 45 evaluable cases was 68,8%, with a complete remission （CR） rate of 37.7%; 3 patients achieved CR after radiotherapy following rituximab-based regimens and 3 achieved CR after autologous hematopoietic stem cell transplantation, The most frequent adverse events were leucopenia, nausea and alopecia. The addition of rituximab to chemotherapy only elevated the occurrence of mild infusion-related reactions, such as chills, fever and pruritus. The median follow-up time was 18 months （range 2-86 months）; 5 patients were lost, 24 were dead （23 died of lymphoma, and 1 died of severe hepatitis）, the other patients remained alive. The median survival time was 32 months （range 2-86 months, 95% confidential interval 16-48 months）. The 1-, 2- and 3-year OS rates were 70.6%, 53,6% and 41,5%, respectively, The median TTP was 6 months （range 0-52 months）, The median PFS was 10 months （range 0-47 months, 95% CI 0-26 months）, The 1- and 2-year PFS were 49,3% and 41,3%. Conclusion： Rituximab-containing salvage regimens are effective and well tolerated therapy for patients with relapsed or refractory B-cell NHL, even those were extensively treated.

Effect of Geometrical Structure on Transport Properties of Silicene Nanoconstrictions

We study electrical modulation of transport properties of silicene nanoconstrictions with different geometrical structures.We investigate the effects of the position and width of the central scattering region on the conductance with increasing Fermi energy.It is found that the conductance significantly depends on the position and the width of the nanoconstriction.Interestingly,the symmetrical structure of the central constriction region can induce a resonance effect and significantly increase the system’s conductance.We also propose a novel two-channel structure with an excellent performance on the conductance compared to the one-channel structure with the same total width.Such geometrically-induced conductance modulation of silicene nanostructures can be achieved in practice via current nanofabrication technology.

Safe Autonomous Docking of Spacecraft:A RRT-combined Output-constrained Recursive Control Method

In addressing the challenges of short-range spacecraft docking in the presence of obstacles and disturbances,it is critical to integrate guidance and motion control to ensure autonomous and reliable operation.Traditional methods that separate these two layers often struggle with accurately tracking predefined paths,increasing the risk of collisions.In light of this,a proposed scheme integrating guidance and control in an organic manner has been put forth.This scheme employs the rapidly-exploring random trees(RRT)algorithm within the guidance layer to generate a collision-avoidance trajectory for the control layer,efficiently navigating the spacecraft towards its target.Then the control layer implements a second-order output-constrained controller by adding a power integrator and a novel barrier Lyapunov function(BLF)together,to guarantee that the tracking error of the predefined trajectory remains bounded and the system asymptotically converges to the target.To account for tracking errors,obstacle radii are expanded during path planning through a dilation constant.Based on theoretical derivation and simulation experiments,the effectiveness and advancement of the proposed method are validated.

湖盆细粒重力流沉积作用过程及甜点层发育机制是什么?

陆相石油是中国石油储量和产量的主要贡献者,陆相石油的勘探对象经历了湖盆区外粗粒沉积储层为主、湖岸线附近粗-中粒沉积储层为主的常规石油,正在向湖盆区内细粒沉积储层为主的非常规页岩油气全面迈进(图1).深湖区发育的以粉砂、泥质粉砂、粉砂质泥、黏土和有机质为主的细粒重力流沉积物(粒径<0.0625 mm),是形成深水(湖)细粒沉积的重要搬运和沉积作用方式(Boulesteix et al.,2019),也是陆相页岩油气富集高产的重要储集甜点层类型(图1).深入研究湖盆细粒重力流体系沉积特征和发育机制,系统认识深湖环境细粒重力流体系沉积作用及演化,不仅对深入理解细粒重力流体系形成的特定地质条件及沉积作用过程、促进湖盆细粒重力流沉积学基础理论的创新发展,而且对湖盆区内页岩油气甜点层预测、富集区评价意义重大.

低预期员工的印象管理行为模型构建

低预期现象在工作场所中十分普遍。然而,过往研究大多关注于低预期的负面影响。本研究基于印象管理理论,构建了低预期员工的印象管理行为模型。当员工感知到自己被寄以低预期时容易产生印象管理动机,从而致力于操控型(自我推销)或建设型(提高任务绩效、组织公民行为)的印象管理行为。低预期员工的这一印象管理过程受到低预期出现的场合、员工的公共自我意识以及员工自身能力和进行印象管理的机会这几个边界条件的制约。本研究在理论上拓展了现有关于低预期研究的理论视角,补充了印象管理理论关于印象管理行为发生的情境因素;在实践方面,为员工处理低预期问题提供了指导性的对策,建议低预期员工不要自暴自弃,可以通过印象管理来改变现状。

Quantitative climatic reconstruction of the Last Glacial Maximum in China

Quantitative paleoclimatic reconstruction is crucial for understanding the operation and evolution of the global climate system.For example,a quantitative paleoclimatic reconstruction for the Last Glacial Maximum(18±2 ka14C,LGM)is fundamental to understanding the evolution of Earth’s climate during the last glacial-interglacial cycle.Previous quantitative palaeoclimate reconstructions in China are generally based on statistical comparison of modern pollen assemblages and modern climate data.These methods are based on the premise that vegetation-climate interactions remain the same through time,and implicitly assume that the interactions are independent of changes in seasonality and atmospheric CO2concentration.However,these assumptions may not always be valid,which may affect the reconstructions.Here,we present the results of a quantitative study of the LGM climate of China based on an improved inverse vegetation model which incorporates physiological processes combined with a new China Quaternary Pollen Database.The results indicate that during the LGM,mean annual temperature(ANNT),mean temperature of the coldest month(MTCO)and mean temperature of the warmest month in China were lower by^5.6±0.8,~11.0±1.6 and^2.6±0.9°C,respectively,compared to today,and that the changes in ANNT were mainly due to the decrease of MTCO.The ANNT decrease in southern China was^5.5±0.5°C.Mean annual precipitation was lower by^46.3±17.8 mm compared to today and was especially low in northern China(~51.2±21.4 mm)due to the decrease in summer rainfall.Comparison of our results with recent outputs from paleoclimatic modelling reveals that while the latter are broadly consistent with our estimated changes in mean annual climatic parameters,there are substantial differences in the seasonal climatic parameters.Our results highlight the crucial importance of developing seasonal simulation on paleoclimatic models,as well as the need to improve the quality of paleoclimatic reconstructions based on proxy records from geological archives.

Characteristics,Types,and Prospects of Geological Sweet Sections in Giant Continental Shale Oil Provinces in China

“Sweet sections”in giant shale oil provinces are preferential fields that primarily support China to increase the reserves and production of continental shale oil.Based on the study of the geological conditions of shale oil in the continental basins in China,it was found that the shale stratum in major oil generation windows generally has higher degrees of oil and gas accumulation,and mostly contains oil.Hydrocarbon generation and reservoir capacities are the two key parameters for evaluating and optimizing favorable shale oil provinces.The evaluation index(volume of shale stratum multiplied by total organic carbon(TOC)multiplied by total porosity)for the giant continental shale oil provinces is also proposed.It is optimized that the Upper Triassic Chang 7 Member in the southcentral Ordos Basin,Lower Cretaceous Qing 1 Member in the Gulong-Changling Sag in the Songliao Basin,Middle-Lower Permian in the Junggar Basin,Da’anzhai Member of the Ziliujing Formation of Lower Jurassic in the central and northern Sichuan Basin,and Paleogene oil-rich sag in the Bohai Bay Basin are the five giant continental shale oil provinces.The word“geological sweet sections”in continental shale oil provinces of China refers to favorable shale intervals which are relatively rich in oil,with superior physical properties,and more easily modified and developed commercially under applicable economic and technological conditions.After evaluation,there are mainly two types of“geological sweet sections”of giant continental shale oil developed onshore in China.One type of“geological sweet sections”is generally mudstone with optimal physical properties or a thin tight reservoir,to which the shale oil migrates a short distance.They are medium-to-high-mature zones with a thin sandy shale stratum in the Chang 7 Member in the Ordos Basin,mixed shale stratum in the mediummature Lucaogou Formation in the Jimsar Sag,and multi-layered mixed Paleogene shale stratum in the Bohai Bay Basin.The other type of“geological sweet sections”is generally shale oil residing in various shale reservoir spaces.This type was developed in the Qing 1 Member in the Gulong Sag and Da’anzhai Member in the north-central Sichuan Basin.Free shale oil mainly occurs in shale,sandycarbonate lamina,micro-lamella structure,and micro-fractures.Layers with lamina,lamination,and micro-fractures are generally shale oil“geological sweet sections.”Starting from field tests and the construction of the“geological sweet sections”in giant continental shale oil provinces,the shale oil industry has been rapidly developing and will become an important supplement to domestic oil production in China.

What are the Lacustrine Fine-Grained Gravity Flow Sedimentation Process and the Genetic Mechanism of Sweet Sections for Shale Oil?

0 INTRODUCTION Oil in continental Basins is the main contributor to petroleum reserves and production in China.The exploration targets of the oil in continental Basins have experienced a transformation from conventional oil,whose reservoirs are mainly composed of coarse-grained deposits outside the lacustrine basin,and coarse-medium-grained sediments deposited near the shoreline of the lacustrine basin.