The Effect of Initial Creep Damage on Unloading Failure Properties of Sandstone from Macro-mesoscopic Perspective

The aim of this research was to show the effect of initial creep damage on unloading failure of rock from macro-mesoscopic perspective. A series of triaxial creep tests were carried out on sandstone to simulate initial creep damage and then unloading confining pressure tests were performed, respectively. A creep damage variable was proposed to analyze the degree of initial creep damage and the relationship of it with the macroscopic strength parameters was established. The results showed that the unloading amount of confining pressure and residual strength all tend to decrease when the degree of initial creep damage increases. The critical challenge was how to describe the effect of initial creep damage from mesoscopic perspective. This aim was achieved through two steps. In the first step, the mesoscopic properties were analyzed using experimentally obtained SEM images of the rock samples with different levels of initial creep damage. By comparative analysis of porosities in different magnifications, it can be concluded that porosity can’t reflect the effect of initial creep damage very well, thus, other pore parameters are further proposed. In the second step, three pore parameters were calculated by using the Matlab and IPP software, then, the average value of mean pore diameter is determined as the proper evaluation parameter and, finally, the agreement was verified between the mesoscopic pore parameter and creep damage variable

Study on Spatial Variation of Shear Mechanical Properties of Soil-rock Mixture

The soil-rock mixture (SRM) is a kind of special engineering geological material, which has been exposed to the field for a long time and is affected by rainwater seepage, geological force, slope sliding force and human activities, resulting in the spatial variability of its mechanical properties. Taking the SRM distributed on a slope of the Three Gorges Reservoir area as the research object, four test locations were selected along and transverse the slope. First, in-situ large-scale direct shear test was carried out, and then the laboratory large-scale direct shear test, particle sieving test, and water content test were carried out in the undisturbed sample to study the variation of shear mechanical properties of SRM distributed in different spatial locations. The results show that: (1) Under the same normal stress, the peak strength of the SRM decreases at a similar rate along the slope direction and the transverse slope direction. (2) The cohesion of the SRM is continuously strengthened, and the friction angle is continuously deteriorated along the slope from high to low, the cohesion and friction angle are almost no variability along the transverse slope. (3) The mechanism of the above-mentioned variation in the shear mechanics parameters of SRM is that the lower the elevation along the slope, the more fragmented the rock, the lower the rock content. (4) Spatial variability models of cohesion and friction angle of SRM were established, which can provide references for related engineering applications

Study on the Time-lag Failure of Sandstone With Different Degrees of Unloading Damage

The unloading effect of rock mass excavation is an inevitable practice, and it’s often characterized by a relatively large-scale engineering hazard with a noticeable time lag.A set of unloading triaxial tests were conducted on a sandstone rock to establish the deformation law and the threshold time. Based on the renormalization group theory, the unloading sandstone model was developed by considering the interaction between particles. Similarly, a logistic model was used to predict the unloading damage of sandstone. The unloading time lag damage of sandstone rock was predicted by using the damage threshold. The research shows that: (1) The higher the degree of unloading, the shorter the time-lag failure. (2) The damage range of critical values was optimized. (3) The error between the predicted value and the experimental value of the time threshold was almost less than 5 %, the prediction result was found to be good, and the employed logistic evolution model was reasonable. The findings of this research provide a prediction method and precise information about the mechanism of unloading time lag deformation. Therefore, it can be used as a reference for excavation-support design of underground structures

Effect of the Water-Rock Interaction on the Creep Mechanical Properties of the Sandstone Rock

After the commencement of the Three Gorges hydropower project, the reservoir water level has been fluctuating by 30 m (145–175 m) annually. The stability of the bank slope has been highlighted since the reservoir water level has been repeated. Apart from that, the long-term effect of the water-rock interaction on the rheological and mechanical properties of the rock was not studied sufficiently. Therefore, a typical sandstone rock was brought from the Three Gorges reservoir area, to meet the purpose of this study. Then, a series of water-rock interaction tests were conducted to simulate the fluctuations in the reservoir water level. Based upon the experimental results, the following points were pointed out: 1) for the first three successive water-rock interaction cycles, the long-term strength of the rock was dramatically reduced. In contrast, the rate of reduction on the long-term strength of the rock was getting a steady state after six successive water rock interactions.2) At the failure stress level, the rock specimens exhibited similar characteristics under different water-rock interaction cycles. 3) The densely compacted micro structures of the sandstone rock were transformed into loose and porous state

New Method for Determination of Residual Strength Parameters and Critical Damage Value

Residual strength and critical damage parameters are worthy to evaluate the stability of engineered rock masses. In this paper, new thinking, repeated load test on a single specimen was proposed to measure the residual strength of the rock. And author proposed to modify the critical damage value based on residual constitutive energy. The test results showed that: (1) the residual strength of rock is mainly controlled by the confining pressure, without a clear relationship with the confining pressure and stress path of the initial loading failure. (2) The residual strength parameters of the rock specimens under repeated loading test are consistent with the conventional triaxial test. Most importantly, the proposed method is relatively less dispersion, cheap, reliable, and time-saving. (3) The corrected critical damage value was reasonable. Relevant test methods can provide a useful reference for the determination of residual strength parameters and critical damage value

Sjögren’s Syndrome Complicated by Myeloid/Natural Killer Cell Precursor Acute Leukemia: Case Report and Review of the Literature

We report a case of Sjögren’s syndrome (SS) complicated by myeloid/natural killer (NK) cell precursor acute leukemia (M/NKPAL). A 75-year-old woman with a previous SS history for 2 years was routinely treated. Peripheral blood progenitor cells were increased, and subsequent bone marrow cell morphology examination showed the presence of acute myeloid leukemia type M4. However, flow cytometry analysis revealed that CD7/CD56/CD33/CD34/HLA-DR/cCD3 were all positive and myeloperoxidase- (MPO-) specific staining, other T cells, NK cells, and myeloid markers were all negative. Clonal T-cell receptor (TCR)β/TCRγ/TCRδ gene rearrangements and Epstein-Barr virus (EBV) were negative. The diagnosis of M/NKPAL was therefore confirmed. Unfortunately, this patient did not receive chemotherapy and later died of acute left heart failure and respiratory failure. SS complication with M/NKPAL is relatively rare. Combined with the relevant literatures, our study offers new insights into the clinical characteristics, pathological features, possible pathogenesis, and differential diagnosis of this rare disease

Regulation of platelet activation and thrombus formation by reactive oxygenspecies

Reactive oxygen species (ROS) are generated within activated platelets and play an important role in regulating platelet responses to collagen and collagen-mediated thrombus formation. As a major collagen receptor, plateletspecific glycoprotein (GP)VI is a member of the immunoglobulin (Ig) superfamily, with two extracellular Ig domains, a mucin domain, a transmembrane domain and a cytoplasmic tail. GPVI forms a functional complex with the Fc receptor γ-chain (FcRγ) that, following receptor dimerization, signals via an intracellular immunoreceptor tyrosine-based activation motif (ITAM), leading to rapid activation of Src family kinase signaling pathways. Our previous studies demonstrated that an unpaired thiol in the cytoplasmic tail of GPVI undergoes rapid oxidation to form GPVI homodimers in response to ligand binding, indicating an oxidative submembranous environment in platelets after GPVI stimulation. Using a redox-sensitive fluorescent dye (H2DCFDA) in a flow cytometric assay to measure changes in intracellular ROS, we showed generation of ROS downstream of GPVI consists of two distinct phases: an initial Syk-independent burst followed by additional Sykdependent generation. In this review, we will discuss recent findings on the regulation of platelet function by ROS, focusing on GPVI-dependent platelet activation and thrombus formation.This research was supported by National Natural Science Foundation of China (grant no. 81400082, 81370602 and 81570096), the Natural Science Foundation of Jiangsu Province (grant no. BK20140219), the funding for the Distinguished Professorship Program of Jiangsu Province, the Six Talent Peaks Project of Jiangsu Province (WSN-133), the Shuangchuang Project of Jiangsu Province, the 333 Project of Jiangsu Province (BRA2017542), the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry, the Science and Technology Foundation for the Selected Overseas Chinese Scholars, State Ministry of Human Resources and Social Security, and the National Health and Medical Research Council of Australi

α-lipoic acid regulate growth, antioxidant status and lipid metabolism of Chinese mitten crab Eriocheir sinensis: Optimum supplement level and metabonomics response

© 2019 Elsevier B.V. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 24 month embargo from date of publication (March 2019) in accordance with the publisher’s archiving policyThe α-lipoic acid (α-LA) is a novel feed additive to improve growth, antioxidant capacity and lipid metabolism in animal husbandry. In this study, isonitrogenous and isoenergetic diets were formulated at seven levels of α-LA (0, 300, 600, 1200, 2400, 4800, or 9600 mg/kg) and fed to the Chinese mitten crab Eriocheir sinensis juveniles for eight weeks. According to weight gain and specific grwoth rate, the optimal level of α-LA supplement in the diet is estimated at 1339–1574 mg/kg for E. sinensis. The α-LA supplement significantly increased the activities of SOD, GSH-Px and T-AOC, and the content of GSH in the hepatopancreas except for SOD in the crabs fed 9600 mg/kg α-LA. Excess dietary α-LA supplement increased the content of MDA in the hepatopancreas. The E. sinensis fed 2400 mg/kg α-LA in the diet showed the highest mRNA expressions of es_TGL1, es_TGL2, es_IL and es_DGL and had higher lipid catabolism when taking 300 mg/kg α-LA than other diets, which coincides with higher mRNA expressions of es_IL, es_DGL and CPT-1 in the hepatopancreas. The crab fed 2400 mg/kg α-LA significantly modified 45 metabolites in serum compared with the control. The supplmentation of α-LA significantly influenced fatty acid metabolism, amino acid metabolism, carnitine metabolism and accumulation of plant antioxidants. This study indicates that α-LA is a promising feed additive to regulate growth, antioxidant status and lipid metabolism in E. sinensis, but its inclusion in the diet should be <2400 mg/kg α-LA to maximize the benefitial effect and minimize side effects

An absence of platelet activation following thalidomide treatment in vitro or in vivo

Increased risk of thromboembolism and platelet hyperreactivity has been reported in patients receiving thalidomide therapy. Whether thalidomide induces platelet activation directly or through other factors remains unclear. The aim of this study was to evaluate the effect of thalidomide on platelet activation under resting conditions in vitro and in vivo. Isolated human or mouse platelets were treated with different concentrations of thalidomide (10, 50 and 100 μg/ml) for 60 min at 37°C followed by analysis of platelet surface expression of platelet receptors GPIbα, GPVI, αIIbβ3 and P-selectin, and PAC-1 or fibrinogen binding, by flow cytometry and collagen- or ADP-induced platelet aggregation. In addition, thalidomide (200 mg/kg) was intraperitoneally injected into mice for analysis of the effect of thalidomide on platelet activation in vivo. No increased expression of P-selectin, PAC-1 or fibrinogen binding was observed in either human and mouse platelets after thalidomide treatment in vitro for 60 min at 37oC. Thalidomide treatment also did not affect expression of GPIbα, GPVI or αIIbβ3, nor did it affect collagen- or ADP-induced platelet aggregation at threshold concentrations. However, while mice injected with thalidomide displayed no increased surface expression of platelet P-selectin or αIIbβ3, there was a significantly shortened tail bleeding time, thrombin time, prothrombin time together with higher levels of Factor IX and fibrinogen. In conclusion, thalidomide at therapeutic doses does not directly induce platelet activation under resting conditions in vitro or in vivo, but results in increased procoagulant activity, which could explain the thalidomide-dependent prothrombotic tendency in patients.This research was supported by National Natural Science Foundation of China (grant no. 81400082 and 81370602), the Natural Science Foundation of Jiangsu Province (grant no. BK20140219), China Postdoctoral Science Foundation funded project (project no. 2015M570479), the funding for the Distinguished Professorship Program of Jiangsu Province, the Six Talent Peaks Project of Jiangsu Province (project no. WSN-133), the Shuangchuang Project of Jiangsu Province, the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry, and the Science and Technology Foundation for the Selected Overseas Chinese Scholars, State Ministry of Human Resources and Social Security

A combination of pre-infusion serum ferritin, CRP and IL-6 predicts outcome in relapsed/refractory multiple myeloma patients treated with CAR-T cells

BackgroundChimeric antigen receptor - T (CAR-T) cell therapy has shown remarkable efficacy in patients with relapsed/refractory multiple myeloma (R/R MM). However, a subset of patients still experienced progression or relapse, and the predictors of prognosis are little known. We analyzed the inflammatory markers before CAR-T cell infusion, to clarify their correlation with survival and toxicity.MethodsThis study involved 109 R/R MM patients who received CAR-T therapy between June 2017 and July 2021. Inflammatory markers, including ferritin, c-reactive protein (CRP), and interleukin-6 (IL-6) before CAR-T cell infusion were detected and then categorized by quartiles. Adverse events and clinical outcomes were compared between patients with upper quartile of inflammatory markers and patients with lower three quartiles of inflammatory markers. An inflammatory prognostic index (InPI) based on these three inflammatory markers was developed in this study. Patients were divided into 3 groups according to the InPI score, progression-free survival (PFS) and overall survival (OS) were compared among the groups. In addition, we explored the correlation between cytokine release syndrome (CRS) and pre-infusion inflammatory markers.ResultsWe found that the pre-infusion high ferritin (hazard ratio [HR], 3.382; 95% confidence interval [CI], 1.667 to 6.863; P = .0007), high CRP (HR, 2.043; 95% CI, 1.019 to 4.097; P = .044), and high IL-6 (HR, 3.298; 95% CI, 1.598 to 6.808; P = .0013) were significantly associated with inferior OS. The formula of the InPI score was based on the HR value of these 3 variables. Three risk groups were formed: (good, 0 to 0.5 point; intermediate, 1 to 1.5 points; poor, 2 to 2.5 points). Median OS for patients with good, intermediate, and poor InPI was not reached, 24 months, and 4 months, respectively, and median PFS was 19.1 months, 12.3 months, and 2.9 months, respectively. In the cox proportional hazards model, poor InPI remained an independent prognostic factor for PFS and OS. Pre-infusion ferritin was negatively associated with CAR T-cell expansion normalized to baseline tumor burden. Spearman correlation analysis showed that pre-infusion ferritin and IL-6 levels positively correlated with the grade of CRS (P = .0369 and P = .0117, respectively). The incidence of severe CRS was higher in patients with high IL-6 compared with patients with low IL-6 (26% vs. 9%, P = .0405). Pre-infusion ferritin, CRP and IL-6 were positively correlated with each peak values within the first month after infusion.ConclusionsOur results suggest that patients with elevated inflammation markers before CAR-T cell infusion are more likely to have poor prognosis