Transferrin-conjugated polymeric nanomedicine to enhance the anticancer efficacy of edelfosine in acute myeloid leukemia

In this study, transferrin (Tf)-conjugated polyethylene glycol (PEG)-poly-l-lysine (PLL)-poly(lactic-co-glycolic acid) (PLGA) (PEG-PLL-PLGA)-based micellar formulations were successfully prepared for the delivery of edelfosine (EDS) in leukemia treatment. The micelles were nanosized and presented spherical shaped particles. Our in vitro data suggest that the nanoformulations maintain the biological activity of drugs for longer periods and lead to a continuous release of active drug. The enhanced cellular uptake of EDS-TM resulted in significantly higher cytotoxic effect in K562 leukemia cells. Cell cycle analysis further demonstrated the significantly higher G2/M phase arrest of cancer cells. Immunoblot analysis clearly revealed the potential of EDS-TM in inducing apoptosis of cancer cells which could improve the anticancer efficacy in leukemia. Importantly, EDS-M and EDS-TM significantly prolonged the circulation profile of EDS throughout until 24 h, indicating the potential of targeted nanoparticulate delivery system. The prolonged blood circulation potential of micellar formulations might improve the therapeutic potential of drug by increasing its bioavailability in the serum. It would be worthwhile evaluating the effects of the EDS-loaded micelles on cancer cells in vivo for clinical application.     

Relation between the development of osteoporosis and osteonecrosis following glucocorticoid in a rabbit model

Background:There has been a recent increase in the number of patients suffering from bone and joint diseases, as a consequence of corticosteroids administration. There are more patients treated with low dose of GCs under long-term conditions in clinical, such as effect of GCs on Rheumatoid arthritis, Crohn''s disease and Asthma patients. Hence, it was difficult for doctor to determine which problem occur first – OP or ON; however, there was no clinical report previously in the literature, and there was no effective animal model of OP and ON about low dose GCs. This study was conducted to develop rabbit models of glucocorticoid (GC)-induced femoral head ON and OP and to investigate the temporal relationship between the occurrence of the two events following administration of glucocorticoids.Results:At 4 weeks in the GC group, the BMD of the femur reduced 33% and 22% in the femoral head and shaft; there was irregular intermediate to high T2-weighted images signals; μ-CT showed microfractures and cystic changes in the femoral head and L4 at 4 weeks. At 8 weeks in the GC group, the classical “line-like sign” indicating ON of the femoral head was observed in 64.3% of the rabbits.Conclusion:A rabbit model of GC-induced OP and ON was developed by repetitive injection with small doses of GCs in the gluteal region. OP was observed at 4 weeks while ON developed at 8 weeks and followed a clear temporal pattern.     

TFPI-2基因在胃癌组织中的表达及临床意义

目的:探讨TFPI-2基因在胃癌组织中的表达及其临床意义。方法:收集临床胃癌患者术后大体标本64例,采用免疫组织化学方法检测TFPI-2蛋白在胃癌组织和正常胃黏膜组织中的表达,采用RT-PCR法检测TFPI-2 mRNA在胃癌组织和正常胃黏膜组织中的表达。结果:TFPI-2蛋白在正常胃黏膜组织中的表达高于胃癌组织(P0.05),无淋巴结转移胃癌组织的TFPI-2蛋白表达高于有淋巴结转移的胃癌组织(P0.05)。TFPI-2 mRNA在正常胃黏膜组织中的表达明显高于胃癌组织(P0.05),无淋巴结转移胃癌组织的TFPI-2 mRNA表达高于有淋巴结转移的胃癌组织(P0.05)。结论:TPFI-2基因是胃癌发生、侵袭和转移的重要调节因子,其低表达与胃癌淋巴结转移的生物学行为密切相关。     

Alveolar macrophage inducible nitric oxide synthase-dependent pulmonary microvascular endothelial cell septic barrier dysfunction

Inducible nitric oxide (NO) synthase (iNOS) from neutrophils and alveolar macrophages (AM) contributes to the pathophysiology of murine septic acute lung injury (ALI). It is not known if AM iNOS has a direct effect on septic pulmonary microvascular endothelial cell (PMVEC) permeability. We hypothesized that AM iNOS mediates PMVEC permeability in vitro under septic conditions through NO and peroxynitrite. 100,000 confluent PMVEC on cell-culture inserts were co-incubated with iNOS+/+ vs. iNOS−/− AM, in various ratios of AM to PMVEC. PMVEC injury was assessed by trans-PMVEC Evans Blue-labelled albumin flux in the presence or absence of cytomix (equimolar TNF-α, IL-1β and IFN-γ). Cytomix stimulation dose-dependently increased trans-PMVEC EB-albumin flux, which was exaggerated (1.4 ± 0.1% vs. 0.4 ± 0.1% in unstimulated PMVEC, p < 0.05) in the presence of iNOS+/+, but not iNOS−/−, AM in the upper compartment. Similarly, iNOS+/+, but not iNOS−/−, AM in the lower compartment also enhanced septic trans-PMVEC albumin leak. The mechanism of iNOS-dependent septic PMVEC permeability was pursued through pharmacologic studies with inhibitors of NOS, and scavengers of NO, superoxide, and peroxynitrite, and treatment of PMVEC with the NO donor, DETA-NONOate. Septic iNOS+/+ AM-dependent trans-PMVEC albumin leak was significantly attenuated by pharmacologic iNOS inhibition (L-NAME and 1400W), and scavenging of either NO (oxyhemoglobin), superoxide (PEG-SOD), or peroxynitrite (FeTPPS). Exogenous NO (DETA-NONOate) had no effect on PMVEC permeability. These data are consistent with a direct role of AM iNOS in septic PMVEC barrier dysfunction, which is likely mediated, in part, through peroxynitrite.     

高分辨率超声检测尺神经直径在肘管综合征中的应用

目的：评价高分辨率超声在肘管综合征诊断及预后中的价值。方法：自2018年1月至2019年6月,采用尺神经松解并皮下前置术的方法治疗47例肘管综合征患者。男41例,女6例;年龄27~73岁;右侧31例,左侧15例,双侧1例。术前、术后应用高分辨率超声检测尺神经直径,术中直观下进行测量,以尺神经功能评定试行标准评估患者恢复状态,并调查患者满意度。结果：47例患者术后切口均为Ⅰ级愈合并全部获得随访,于出院后12个月进行随访。术前尺神经受压部位的直径（0.16±0.04） cm,术后为（0.23±0.04） cm。尺神经功能评定结果：优16例,良18例,可13例。术后12个月满意度结果：满意28例,一般10例,不满意9例。结论：高分辨率超声术前检查与术中直观测量一致,术后高分辨率超声检查结果与随访结果一致,高分辨率超声为肘管综合征诊治的有效辅助手段。     

Glycosyltransferases and non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD) is the most common form of chronic liver disease and its incidence is increasing worldwide. However, the underlying mechanisms leading to the development of NAFLD are still not fully understood. Glycosyltransferases(GTs) are a diverse class of enzymes involved in catalyzing the transfer of one or multiple sugar residues to a wide range of acceptor molecules. GTs mediate a wide range of functions from structure and storage to signaling, and play a key role in many fundamental biological processes. Therefore, it is anticipated that GTs have a role in the pathogenesis of NAFLD. In this article, we present an overview of the basic information on NAFLD, particularly GTs and glycosylation modification of certain molecules and their association with NAFLD pathogenesis. In addition, the effects and mechanisms of some GTs in the development of NAFLD are summarized.     

儿童重症肺炎的实验室检查结果分析

目的研究肺炎支原体感染所致的重症肺炎的实验室检查结果,探讨相关危险因素。方法回顾性分析济宁市第一人民医院2018年6月1日至2019年6月1日收治的肺炎支原体感染导致的大叶性肺炎患儿的临床资料,其中确诊为重症肺炎的患儿设为重症组(46例),确诊为非重症肺炎的患儿设为对照组(30例),分析并比较两组患儿的病原学检查等结果。结果重症组C反应蛋白(CRP)、降钙素原(PCT)、D-二聚体、谷丙转氨酶(ALT)、乳酸脱氢酶(LDH)水平及肺炎支原体DNA(MP-DNA)、MP-IgM滴度均高于对照组(Z值分别为-2.120、-2.418、-2.159、-2.749、-2.192、-2.834、-2.587,均P<0.05),白蛋白(ALB)水平低于对照组(t=2.485,P<0.05)。多因素Logistic回归分析结果显示,MP-DNA滴度是重症肺炎的独立影响因素,OR=2.074,95%CI:1.161~3.704,表明随着MP-DNA浓度越高,发生重症肺炎的风险越大。ROC曲线分析结果显示,MP-DNA拷贝数大于4.47时,预测重症肺炎的灵敏度和特异度分别为50.00%和96.67%;当MP-IgM滴度大于1∶640时预测重症肺炎的灵敏度和特异度分别为43.48%和93.33%。结论D-二聚体、PCT、CRP、ALT、LDH升高及白蛋白降低有助于识别重症肺炎,MP-DNA是重症肺炎发生的独立影响因素。     

A Prolonged Nitric Oxide-Dependent,Opioid-Mediated Antinociceptive Effect of Hyperbaric Oxygen in Mice

Hyperbaric oxygen (HBO₂) therapy is reported to cause pain relief in several conditions of chronic pain. A single 60-minute session of HBO₂ treatment produced a prolonged antinociceptive effect in mice that persisted for 90 minutes after cessation of treatment. The HBO₂-induced antinociception was significantly attenuated by pretreatment before HBO₂ exposure with the opioid antagonist naltrexone, the nonspecific nitric oxide synthase (NOS)-inhibitor N^G-nitro-l-arginine methyl ester (L-NAME), and the selective neuronal NOS-inhibitor S-methyl-l-thiocitrulline (SMTC) but not the selective endothelial NOS-inhibitor N⁵-(1-iminoethyl)-l-ornithine (L-NIO). The antinociception was also significantly reduced by central pretreatment with a rabbit antiserum against dynorphin_1-13 but not by rabbit antisera against either β-endorphin or methionine-enkephalin. The prolonged antinociceptive effect at 90 minutes after HBO₂-induced treatment was also significantly attenuated by naltrexone but not L-NAME administered 60 minutes after HBO₂ treatment but before nociceptive testing. These findings indicate that the antinociception that persists for 90 minutes after HBO₂ exposure is mediated by nitric oxide (NO) and opioid mechanisms but that the NO involvement is critical during the HBO₂ treatment and not at the time of nociceptive testing. These results are consistent with the concept that HBO₂ may induce an NO-dependent release of opioid peptide to cause a long-acting antinociceptive effect.PerspectiveThis article presents evidence of a persistent antinociceptive effect of hyperbaric oxygen treatment that is mediated by opioid and NO mechanisms. Further elucidation of the underlying mechanism could identify molecular targets to cause a longer-acting activation of endogenous pain-modulating systems.