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BACKGROUND T-cell large granular lymphocytic leukemia (T-LGLL) is a rare type of aplastic anemia with diverse clinical manifestations. Concomitant diseases are often present at the first manifestation. We describe the treatment of a patient with CD57-negative γδT-LGLL with pure red cell aplasia (PRCA). CASE SUMMARY A 34-year-old woman with a 20-year history of anemia visited our hospital owing to severe dizziness and was admitted. Her condition was diagnosed as CD57-negative γδT-LGLL with PRCA through bone marrow cytology, bone marrow pathology, bone marrow flow cytometry, bone marrow multiplex polymerase chain reaction combined with fluorescent fragment analysis, and other tests. Treatment with prednisone, methotrexate, and subcutaneous erythropoietin did not significantly change her hemoglobin level. After treatment with oral cyclophosphamide for 3 mo, her hemoglobin level increased to approximately 100 g/L. After 5 mo of treatment, the patient could perform activities of daily living independently. CONCLUSION The treatment of CD57-negative γδT-LGLL with PRCA with cyclophosphamide helps to improve prognosis.

Purpose Ixazomib is a selective, effective, and reversible inhibitor of 20S proteasome and is approved for the treatment of multiple myeloma. Ubiquitin-conjugating enzyme E2 (UBE2K) is involved in the synthesis of K48-linked ubiquitin chains and is the target of certain drugs used for the treatment of tumors. The purpose of this study was to investigate the relationship between ixazomib and UBE2K in myeloma cells. Methods We used CCK-8 and Annexin V-FITC/propidium iodide kit to detect the effects of ixazomib on survival and apoptosis of RPMI-8226 and U-266 myeloma cell lines. Quantitative polymerase chain reaction and western blot were used to detect the change in gene and protein expression levels of myeloma cells treated with ixazomib. Furthermore, the regulatory effects of ixazomib on UBE2K and its downstream targets were investigated following the overexpression of UBE2K. Results In myeloma cells, ixazomib decreased cell survival and increased apoptosis in a dose-dependent manner. Ixazomib significantly increased the expression of HIST1H2BD, MNAT1, NEK3, and TARS2, while decreasing the expression of HSPA1B and UBE2K. In addition, ixazomib inhibited the proliferation of myeloma cells, blocked cell cycle, induced cell apoptosis, and increased the production of reactive oxygen species by inhibiting UBE2K expression. Lastly, ixazomib regulates mitosis- and apoptosis-related genes by lowering UBE2K expression. Conclusion In summary, ixazomib leads to impaired proliferation of myeloma cells by targeting UBE2K.

To investigate the efficacy of disease control, survival time and safely in treatment of newly diagnosed multiple mycloma patients with different dose of tenalidomide regimens.The clinical data of 116 patients with multiple myeloma from June 2011 to June 2015 were collected and analyzed retrospectively. According to doses of used lenalidomide based on dexamethasone plus lenalidomide regimen 116 patients were divided into 2 groups: conventional dose group (58 cases) and low dose group (58 cases). The ORR, PFS rate and OS rate during followed-up for 3 years, KPS score, RNS score and immunophenotypic index before and after treatment and drug toxicity incidence were compared between 2 groups.The ORR for 2 treatment courses of low dose group was significantly lower than that in conventienal dose group (P＜0.05). The ORR for 4 and 6 treatment courses was not significantly different between 2 groups (P＞0.05). The PFS rate and OS rate during followed-up for 3 years was no significantly different between 2 groups (P＞0.05). The KPS score and RNS score after treatment of low dose group were significantly better than those in conventional dose group and before treatment (P＜0.05). The levels of immunophenotypic index after treatment of both groups were significantly better than those before treatment (P＜0.05). The incidence of III-IV grade hematological toxicity, pulmonary infection and herpes were not significantly different between 2 groups (P＞0.05). The incidence of peripheral neuropathy and gastrointestinal reactions in the low dose group were significantly lower than that in conventional dose group (P＜0.05).Conventional and low doses of lenalidomide possess the same control effects and survival time for treatment of newly dingnosed patients with multiple myeloma; Despite, the initiation of effects from the low dose lenalidomide is relatively slower, it contributes to raise the overall quality of life and reduce the risk of drug toxicity.不同剂量来那度胺治疗初治多发性骨髓瘤患者的疾病控制效果、生存时间及安全性.探讨常规剂量和低剂量来那度胺治疗初治多发性骨髓瘤患者的疾病控制效果、生存时间及安全性.收集并回顾性分析2011年6月- 2015年6月收治的初治多发性骨髓瘤患者116例临床资料，在地塞米松+来那度胺基础上，按来那度胺给药剂量不同分为常规剂量组（58例）和低剂量组（58例）。比较2组ORR、随访3年PFS率和OS率、治疗前后KPS评分、RNS评分、免疫表型指标水平及毒副作用的发生率.低剂量组2个疗程ORR显著低于常规剂量组（P＜0.05）；2组4个和6个疗程ORR比较无显著性差异（P＞0.05）；2组随访3年PFS率和OS率比较无显著性差异（P＞0.05）；低剂量组患者治疗后KPS评分和RNS评分均显著优于治疗前（P＜0.05）；2组患者治疗后免疫表型指标水平均显著优于治疗前（P＜0.05）；但2组治疗后免疫表型指标水平组间比较无显著性差异（P＞0.05）；同时2组III-IV度白细胞减少、周围神经病变、消化道反应、肺部感染及疱疹发生率比较无显著性差异（P＞0.05）；低剂量组中性粒细胞减少和血小板减少发生率均显著低于常规剂量组（P＜0.05）.常规剂量和低剂量来那度胺方案用于初治多发性骨髓瘤患者治疗具有相近疾病控制效果和生存时间；其中低剂量来那度胺方案尽管早期起效相对缓慢，但有助于提高总体生存质量，减低毒副作用发生风险.

Soft rock is frequently encountered in underground excavation process. It is difficult to excavate and support in soft rock mass which has low strength, large deformation and needs much time to be out of shape but little time to be self-stabilized. Based on a large underground power station, finite element model analysis was carried out to simulate the excavation process and the results of displacement, stress and plasticity area were compared between supported and unsupported conditions to evaluate the stability of the rock mass.

The simulation of solute transport in fractured rock mass has been conducted with the Finite Difference Method(FDM), Finite Element Method(FEM) and Finite Analysis Method(FAM), etc.. However, groundwater flow and solute transport is very complex in fractured network compared to the rocks matrix because water flow and tracer particles have different selections of pathways when they travel to the fractured intersections. It is difficult for traditional method to simulate the law of solute transport in fractured network. Hence a new simulation method, the probability method, is developed. In the method, transfer probabilities for fractured network are calculated using the flux of input and output from fractured intersection points, and travel times of tracer particles are determined with random numbers, dispersion parameter and velocity. Furthermore, corresponding computing program is developed using the FORTRAN language. The comparison between simulated and experimental results shows that the probability method is of considerable reliability and is an effective method to simulate solute transport in fractured network, and the case study of the Jinping I-Hydropower Station displays its wide application prospect.

The purpose of this study was to investigate the lethal effect of cytotoxic lymphocytes against U266 cells induced by DCs pulsed with multiple myeloma (MM) U266 lysate and transfected with GM-CSF recombinant adenovirus. The cytotoxic lymphocytes against U266 cells were induced by culturing with DCs, which pulsed with MM U266 antigens and transfected with GM-CSF recombinant adenovirus. The effect of cytotoxic lymphocytes against U266 cells were measured by LDH release detection. Experiments were divided into 3 groups: N-DC group as control in which DCs were normal; U-DC group in which DCs were pulsed by U266 soluble antigen, and G-U-DC group in which DCs were stimulated by U266 soluble antigen and GM-CSF transfected with Ad-CMV. The results showed that there was significant difference on killing rate against U266 cells between 3 groups (F = 10.939, p0.05). The killing rate of G-U-DC group was the highest (p0.001), and killing rate of U-DC group was higher than that of N-DC group (p0.001). It is concluded that the cytotoxic lymphocytes against U266 cells can be induced by DCs pulsed with U266 lysate, and the lethal effect of CTLs can be enhanced when DCs transfected by recombinant adenovirus with exogenous gene GM-CSF.