CD5-low expression lymphocytes in canine peripheral blood show characteristics of natural killer cells

NK cell markers and receptors have been discovered in many mammalian species, such as humans, mice, rats, pigs, and cows. However, there is still a lack of information concerning NK cell markers or receptors in canines. We have discovered that canine CD5-low density (CD5lo) cells in PBL are closely associated with NK cell characteristics. CD5lo cells comprised 14.9 +/- 6.68% of the total PBL. A high proportion of the CD5lo cell population expressed CD3 (96.6%), CD8alpha (77.7%), CD8beta (53%), alpha/beta TCR (83%), and CD11/18 (80%), but the expression of gamma/delta TCR (6.5%), CD4 (10.6%), and CD21 (2.4%) was low. CD5lo cells were larger than CD5-high density (CD5hi) cells. Light and electron microscopy revealed numerous large cytoplasmic granules in CD5lo cells, especially after IL-2 stimulation, which was in contrast to CD5hi, in which intracytoplasmic granules were not frequently seen. After IL-2 stimulation, CD5lo cells had significantly stronger NK cytotoxicity than CD5hi cells. CD5lo cells had much higher mRNA levels for NKG2D, CD16, CD94, CD160, perforin, and granzyme than CD5hi. Following IL-2 stimulation, CD5lo cells had significantly higher mRNA levels of NKp30, NKp44, CD16, and CD94 than CD5hi cells. In addition, IL-2-stimulated, CD5lo-depleted PBL showed a loss of NK cytotoxicity. CD5lo cells also showed significantly lower antigen-specific cytotoxic T cell activity as compared with CD5hi cells. Taken together, the CD5lo subset in canine PBL is closely related to canine NK cells, and CD5lo can be used as a phenotypic marker for an IL-2-dependent canine NK cell enrichment.     

江苏地区无偿献血人群巴贝虫感染调查

目的　了解江苏地区无偿献血人群巴贝虫感染情况,为输血安全提供科学依据。方法　2017年2–5月对江苏省血液中心采集的950人份无偿献血者血样,以巴贝虫分泌抗原（BmSA1）为诊断靶标分子,采用双抗原夹心酶联免疫吸附试验（ELISA）检测单份血清标本靶向巴贝虫特异性总抗体水平,对抗体阳性样品制作血涂片进行镜检,并提取DNA进行巢式PCR扩增确认寄生虫血症;分析不同性别、年龄和职业献血者巴贝虫抗体阳性率。结果　江苏地区950人份无偿献血人群巴贝虫抗?BmSA1抗体阳性率为0.53%,5例巴贝虫抗?BmSA1抗体阳性血样镜检和巢式PCR结果均为阴性。不同性别（[χ2] = 0.01,P = 0.92）和年龄（[χ2] = 0.11,P = 0.95）献血者巴贝虫抗?BmSA1抗体阳性率间差异均无统计学意义,但不同职业献血者巴贝虫抗?BmSA1抗体阳性率间差异具有统计学意义（[χ2] = 11.93,P < 0.05）。结论　江苏地区无偿献血者中有巴贝虫感染者,应予以重视。     

北京市丰台区民营医院发展现状及对策研究

抽取了北京市丰台区7家民营医院,采用定性访谈和问卷调查方式,分析了民营医院自身的优势、存在的问题以及面临的制约因素,提出了完善职称晋升、医保定点及税收政策,加强与民营医院的沟通,加强对民营医院的监管等措施,为如何更好地引入社会资本提供参考建议。     

Effect of hydrogen sulphide on beta-amyloid-induced damage in PC12 cells

1. Hydrogen sulphide (H(2)S) is a well-known cytotoxic gas. Recently, H(2)S has been shown to protect neurons against oxidative stress caused by glutamate, peroxynitrite and HOCl. Considerably lower H(2)S levels have been reported in the brain of Alzheimer's disease (AD) patients with accumulation of beta-amyloid (A beta). 2. The aim of present study was to explore the cytoprotection by H(2)S against A beta(25-35)-induced apoptosis and the molecular mechanisms underlying this effect in PC12 cells. 3. Our findings indicated that A beta(25-35) significantly reduced cell viability and induced apoptosis of PC12 cells, along with dissipation of the mitochondrial membrane potential (MMP) and overproduction of reactive oxygen species (ROS). 4. Sodium hydrosulphide (NaHS), an H(2)S donor, protected PC12 cells against A beta(25-35)-induced cytotoxicity and apoptosis not only by reducing the loss of MMP, but also by attenuating the increase in intracellular ROS. 5. The results of the present study suggest that the cytoprotection by H(2)S is related to the preservation of MMP and attenuation of A beta(25-35)-induced intracellular ROS generation. These findings could significantly advance therapeutic approaches to the neurodegenerative diseases that are associated with oxidative stress, such as AD.     

Iron Overload Exacerbates Busulfan-Melphalan Toxicity Through a Pharmacodynamic Interaction in Mice

Purpose

Busulfan-melphalan high-dose chemotherapy followed by autologous stem cell transplantation is an essential consolidation treatment of high-risk neuroblastoma in children. Main treatment limitation is hepatic veno-occlusive disease, the most severe and frequent extra-hematological toxicity. This life threatening toxicity has been related to a drug interaction between busulfan and melphalan which might be increased by prior disturbance of iron homeostasis, i.e. an increased plasma ferritin level.

Methods

We performed an experimental study of busulfan and melphalan pharmacodynamic and pharmacokinetics in iron overloaded mice.

Results

Iron excess dramatically increased the toxicity of melphalan or busulfan melphalan combination in mice but it did not modify the clearance of either busulfan or melphalan. We show that prior busulfan treatment impairs the clearance of melphalan. This clearance alteration was exacerbated in iron overloaded mice demonstrating a pharmacokinetic interaction. Additionally, iron overload increased melphalan toxicity without altering its pharmacokinetics, suggesting a pharmacodynamic interaction between iron and melphalan. Based on iron homeostasis disturbance, we postulated that prior induction of ferritin, through Nrf2 activation after oxidative stress, may be associated with the alteration of melphalan metabolism.

Conclusion

Iron overload increases melphalan and busulfan-melphalan toxicity through a pharmacodynamic interaction and reveals a pharmacokinetic drug interaction between busulfan and melphalan.

     

Genomic characterisation of breast fibroepithelial lesions in an international cohort

Fibroepithelial lesions (FELs) are a heterogeneous group of tumours comprising fibroadenomas (FAs) and phyllodes tumours (PTs). Here we used a 16-gene panel that was previously discovered to be implicated in pathogenesis and progression, to characterise a large international cohort of FELs via targeted sequencing. The study comprised 303 (38%) FAs and 493 (62%) PTs which were contributed by the International Fibroepithelial Consortium. There were 659 (83%) Asian and 109 (14%) non-Asian FELs, while the ethnicity of the rest was unknown. Genetic aberrations were significantly associated with increasing grade of PTs, and were detected more in PTs than FAs for MED12, TERT promoter, RARA, FLNA, SETD2, TP53, RB1, EGFR, and IGF1R. Most borderline and malignant PTs possessed ≥ 2 mutations, while there were more cases of FAs with ≤ 1 mutation compared to PTs. FELs with MED12 mutations had significantly higher rates of TERT promoter, RARA, SETD2, EGFR, ERBB4, MAP3K1, and IGF1R aberrations. However, FELs with wild-type MED12 were more likely to express TP53 and PIK3CA mutations. There were no significant differences observed between the mutational profiles of recurrent FAs, FAs with a history of subsequent ipsilateral recurrence or contralateral occurrence, and FAs without a history of subsequent events. We identified recurrent mutations which were more frequent in PTs than FAs, with borderline and malignant PTs harbouring cancer driver gene and multiple mutations. This study affirms the role of a set of genes in FELs, including its potential utility in classification based on mutational profiles. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

生乳香及醋制品对家兔血小板粘附作用的比较

目的：探讨乳香及醋制前后对动物血小板粘附性的影响。方法：用体外血小板粘附率测定法测定血小板粘附性。结果：醋制后乳香降低血小板粘附作用加强。结论：乳香生用活血,醋制祛瘀。     

Experimental and In Silico Analysis of Cordycepin and its Derivatives as Endometrial Cancer Treatment

The aim of this study was to investigate the inhibition effects of cordycepin and its derivatives on endometrial cancer cell growth. Cytotoxicity MTT assays, clonogenic assays, and flow cytometry were used to observe the effects on apoptosis and regulation of the cell cycle of Ishikawa cells under various concentrations of cordycepin, cisplatin, and combinations of the two. Validated in silico docking simulations were performed on 31 cordycepin derivatives against adenosine deaminase (ADA) to predict their binding affinities and hence their potential tendency to be metabolized by ADA. Cordycepin has a significant dose-dependent inhibitory effect on cell proliferation. The combination of cordycepin and cisplatin produced greater inhibition effects than did cordycepin alone. Apoptosis investigations confirmed the ability of cordycepin to induce the apoptosis of Ishikawa cells. The in silico results indicate that compound MRS5698 is least metabolized by ADA and has acceptable drug likeness and safety profiles. This is the first study to confirm the cytotoxic effects of cordycepin on endometrial cancer cells. This study also identified cordycepin derivatives with promising pharmacological and pharmacokinetic properties for further investigation in the development of new treatments for endometrial cancer     

慢性丙型肝炎病毒感染献血者多项感染指标相关性分析

目的了解 HCV 感染的献血者疾病进程和健康状况。方法通过多项感染指标的监测,包括抗-HCV、HCV-RNA、ALT 和肝组织病理改变等项目检查,分析这些指标的相关性。结果 HCV-RNA 定量、抗-HCV 强度、ALT 水平和肝组织病理变化有明显相关性。结论 HCV-RNA 定量,抗-HCV 强度,ALT 水平和肝组织病理变化等项目的分析,都是了解HCV 感染者健康状况和监测疾病进程的合适重要指标。