Efficacy and Feasibility of Allogeneic Hematopoietic Stem-Cell Transplantation in the Treatment of Refractory Acute Myeloid Leukemia

Background

Refractory acute myeloid leukemia (AML) includes AML includes failure of disease to respond to standard induction chemotherapy, relapse within 6 months after first CR, and 2 or more relapses. The outcome of these patients is usually very poor; only a small proportion can be rescued by allogenic hematopoietic stem-cell transplantation (allo-HSCT). The aim of this study was to evaluate the efficacy and feasibility of allo-HSCT in patients with refractory AML.

白鲜皮多糖的分离纯化及抗银屑病作用

目的:对白鲜皮粗多糖(DDP)进行分离纯化,并研究其抗银屑病作用。方法:DDP经膜分离技术截留相对分子质量小于10 k Da的组分(DDP-UF),采用DEAE-52纤维素柱分离纯化得到4种组分(DDP-UF-1,DDP-UF-2,DDP-UF-3,DDPUF-4);并通过红外光谱法,高效凝胶渗透色谱法(HPGPC),高效液相色谱法(HPLC),扫描电镜(SEM)测定其理化性质及结构特征。选用咪喹莫特乳膏诱导银屑病小鼠模型,己烯雌酚诱导雌鼠阴道上皮细胞增殖,酶联免疫吸附测定法(ELISA)检测各组小鼠血清白细胞介素(IL)-17与IL-23含量,苏木精-伊红(HE)染色法观察小鼠背部皮肤组织病理变化、阴道上皮细胞有丝分裂指数变化。结果:DDP-UF-1～4均具有多糖特征吸收峰,DDP-UF-1～4相对分子质量分别为10 948,40 148,32 222,19 943 Da;单糖组成及摩尔比分别为甘露糖-葡萄糖-半乳糖(32. 45∶11. 35∶8. 69),甘露糖-鼠李糖-葡萄糖醛酸-葡萄糖-木糖(25. 68∶23. 44∶21. 62∶18. 86∶3. 68),甘露糖-鼠李糖-葡萄糖醛酸-半乳糖醛酸-木糖-半乳糖(18. 68∶4. 61∶3. 89∶1. 65∶5. 36∶6. 21),葡萄糖醛酸-半乳糖醛酸-葡萄糖-木糖-半乳糖(11. 63∶15. 26∶5. 32∶2. 08∶3. 46);扫描电镜(SEM)显示DDP-UF-1～4形态结构为片状或海绵状结构。DDP-UF-1与DDP-UF-3可改善银屑病小鼠背部皮损状态、抑制雌鼠阴道上皮细胞有丝分裂、明显降低血清IL-17,IL-23含量(P 0. 05,P 0. 01)。结论:DDP-UF-1与DDP-UF-3均具有良好的抗银屑病作用,其作用可能与抑制IL-23/IL-17信号通路有关。     

C.B‐17 SCID mice develop epicardial calcinosis with unaltered cardiac function

Inbred mouse strains are the most widely used mammalian model organism in biomedical research owing to ease of genetic manipulation and short lifespan; however, each inbred strain possesses a unique repertoire of deleterious homozygous alleles that can make a specific strain more susceptible to a particular disease. In the current study, we report dystrophic cardiac calcinosis (DCC) in C.B‐17 SCID male mice at 10 weeks of age with no significant change in cardiac function. Acquisition of DCC was characterized by myocardial injury, fibrosis, calcification, and necrosis of the tissue. At 10 weeks of age, 38% of the C.B‐17 SCID mice from two different commercial colonies exhibited significant calcinosis on the ventricular epicardium, predominantly on the right ventricle. The frequency of calcinosis was more than 50% for mice obtained from Taconic's Cambridge City colony and 25% for mice obtained from Taconic's German Town colony. Interestingly, the DCC phenotype did not affect cardiac function at 10 weeks of age. No differences in echocardiography or electrocardiography were observed between the calcinotic and non‐calcinotic mice from either colony. Our findings suggest that C.B‐17 SCID mice exhibit DCC as early as 10 weeks of age with no significant impact on cardiac function. This strain of mice should be cautiously considered for the study of cardiac physiology.     

Attenuated Novel SARS Coronavirus 2 Infection in an Allogeneic Hematopoietic Stem Cell Transplant Patient on Ruxolitinib

Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) has a high death rate in patients with comorbidities or in an immunocompromised state. We report a mild and attenuated SARS CoV-2 infection in a patient who is 17 months post stem cell transplantation and maintained on the JAK/STAT inhibitor ruxolitinib, a proposed novel therapy for SARS CoV-2 pneumonia.     

A new mouse model for the neurodevelopmental ciliopathy Joubert syndrome

Recent recognition of the key role of primary cilia in orchestrating human development and of the dire consequences of their dysfunction on human health has placed this small organelle in the spotlight. While the causal link between mutations in ciliary genes and central nervous system malformations and dysfunction is well established, the mechanisms by which primary cilia dysfunction acts on development and function of the CNS remain partly unknown. The recent article by Bashford and Subramanian in The Journal of Pathology describes a new mouse model for the neurodevelopmental ciliopathy Joubert syndrome, supporting a role for ciliary-mediated Hedgehog signaling on proliferation, survival, and differentiation of cerebellar granule cell progenitors. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

2‐deoxy D‐glucose treatment does not elicit a hair growth response in alopecia areata

2‐deoxy D‐glucose (2DG) was tested for efficacy in treating alopecia areata using the C3H/HeJ skin graft model. 2DG has proven to be efficacious in treatment of various mouse models of autoimmunity with minimal serious side effects noted. This agent has been shown to normalize abnormally activated T‐cell populations while also preventing cell surface expression of NKG2D; key factors defining alopecia areata disease progression. Daily oral ingestion of 2DG via drinking water to mice with patchy or diffuse alopecia areata for 16 weeks failed to prevent expansion of alopecia or cause regrowth of hair in treated mice. Histologically, there were no differences between treated and control groups. These results indicate that, while 2DG is effective for some autoimmune diseases, it was not efficacious for the cell‐mediated autoimmune mouse disease, alopecia areata.     

ELAM-1在鼻咽癌裸鼠移植瘤中的表达及其与转移的关系

目的 建立裸鼠鼻咽癌转移模型并探讨 E-选择素（ELAM-1）与鼻咽癌转移的相关性。方法 将鼻咽癌5-8F细胞悬液注射于裸鼠左后肢爪垫，观察裸鼠状态、成瘤情况并测量裸鼠体重及移植瘤长短径；采用连续病理切片苏木精-伊红染色观察移植瘤及转移情况，将16只人鼻咽癌荷瘤裸鼠分为转移组和非转移组；采用免疫组织化学法检测两组移植瘤组织中ELAM-1的表达。 结果 16只裸鼠均成瘤，成瘤率为100.0%，其中10只裸鼠出现转移瘤，转移率为62.5%。建模前，两组裸鼠体重差异无统计学意义［（13.83±0.56）g vs （14.62±0.30） g，t=1.026，P=0.071］。建模后4~7周，裸鼠瘤体体积呈指数增长，且转移组移植瘤增长速度较非转移组快，非转移组裸鼠瘤体体积小于转移组［（198.91 ± 163.29） mm³ vs （268.76 ±174.31） mm³，t=4.376，P=0.005］。ELAM-1在鼻咽癌裸鼠移植瘤、淋巴结转移灶及远处转移灶中的表达均为阳性，主要表达于细胞膜。转移组移植瘤光密度值高于非转移组（0.4497±0.0705 vs 0.0435±0.0082，t=4.388，P＝0.001）。结论 本研究成功构建稳定性好、转移率高的鼻咽癌裸鼠移植瘤转移模型，且ELAM-1在裸鼠移植瘤中高表达，可促进鼻咽癌裸鼠移植瘤生长和转移。