Propofol inhibits the malignant development of osteosarcoma U2OS cells via AMPK/FΟΧO1-mediated autophagy

It has previously been reported that propofol regulates the development of human osteosarcoma (OS). However, the specific molecular mechanisms underlying the effect of propofol on OS remain poorly understood. Therefore, the aim of the present study was to explore the effects of propofol on OS U2OS cells and the potential underlying mechanism. The Cell Counting Kit-8 and colony formation assays were performed to assess cell viability and proliferation. Furthermore, cell apoptosis was assessed using the TUNEL assay and western blotting. Wound healing and Transwell assays were performed to evaluate OS cell migration and invasion abilities, respectively. The protein expression levels of epithelial-mesenchymal transition (EMT)-, autophagy- and adenosine monophosphate-activated protein kinase (AMPK)/FOXO1 signaling pathway-related proteins were also determined using western blotting. The results demonstrated that propofol significantly reduced the viability of OS cells and promoted autophagy in a dose-dependent manner. Moreover, cell treatment with propofol significantly enhanced the protein expression levels of phosphorylated (p)-AMPK and FOXO1, while decreasing the protein levels of p-FOXO1. Furthermore, treatment with propofol significantly suppressed cell viability, migration and invasion abilities and the EMT of OS cells, and potentially promoted cell apoptosis via inducing autophagy via the AMPK/FOXO1 signaling pathway. In summary, the present study indicated that propofol potentially had an inhibitory effect on the development of OS cells via AMPK/FOXO1-mediated autophagy. These results have therefore provided an experimental basis for further studies into the therapeutic effect of propofol on OS.     

Development and Characterizations of Pullulan and Maltodextrin-Based Oral Fast-Dissolving Films Employing a Box–Behnken Experimental Design

Migraine is a neurological disorder characterized by severe headaches, visual aversions, auditory, and olfactory disorders, accompanied by nausea and vomiting. Zolmitriptan (ZMT^®) is a potent 5HT1B/1D serotonin receptor agonist frequently used for the treatment of migraine. It has erratic absorption from the gastrointestinal tract (GIT), but its oral bioavailability is low (40–45%) due to the hepatic metabolism. This makes it an ideal candidate for oral fast dissolving formulations. Hence, the current study was undertaken to design and develop oral fast-dissolving films (OFDFs) containing ZMT for migraine treatment. The OFDFs were formulated by the solvent casting method (SCM) using Pullulan (PU) and maltodextrin (MDX) as film-forming agents and propylene glycol (PG) as a plasticizer. The strategy was designed using Box–Behnken experimental design considering the proportion of PU:MDX and percentage of PG as independent variables. The effectiveness of the OFDF’s was measured based on the following responses: drug release at five min, disintegration time (D-time), and tensile strength (TS). The influence of formulation factors, including percent elongation (%E), thickness, water content, moisture absorption, and folding endurance on ZMT-OFDFs, were also studied. The results showed a successful fabrication of stable ZMT-OFDFs, with surface uniformity and amorphous shape of ZMT in fabricated films. The optimized formulation showed a remarkable rapid dissolution, over 90% within the first 5 min, a fast D-time of 18 s, and excellent mechanical characteristics. Improved maximum plasma concentration (C max) and area under the curve (AUC 0–t) in animals (rats) treated with ZMT-OFDFs compared to those treated with an intra-gastric (i-g) suspension of ZMT were also observed. Copolymer OFDFs with ZMT is an exciting proposition with great potential for the treatment of migraine headache. This study offers a promising strategy for developing ZMT-OFDFs using SCM. ZMT-OFDFs showed remarkable rapid dissolution and fast D-time, which might endeavor ZMT-OFDFs as an auspicious alternative approach to improve patient compliance and shorten the onset time of ZMT in migraine treatment.     

Inactivation Methods for Experimental Nipah Virus Infection

Nipah virus (NiV) is an emerging zoonotic paramyxovirus that causes severe disease in humans and livestock. Due to its high pathogenicity in humans and the lack of available vaccines and therapeutics, NiV needs to be handled in biosafety level 4 (BSL-4) laboratories. Safe inactivation of samples containing NiV is thus necessary to allow further processing in lower containment areas. To date, there is only limited information available on NiV inactivation methods validated by BSL-4 facilities that can be used as a reference. Here, we compare some of the most common inactivation methods in order to evaluate their efficacy at inactivating NiV in infected cells, supernatants and organs. Thus, several physical and chemical inactivation methods, and combinations thereof, were assessed. Viral replication was monitored for 3 weeks and NiV presence was assessed by RT-qPCR, plaque assay and indirect immunofluorescence. A total of nineteen methods were shown to reduce NiV infectious particles in cells, supernatants and organs to undetectable levels. Therefore, we provide a list of methods for the safe and efficient inactivation of NiV.     

热环境对机体功能影响的机制及防护研究进展

热环境增加高温作业人员发生热损伤的风险,充分认识热环境对高温作业人员机体的影响和危害,对提高高温作业人员防暑意识、减少作业时的职业性热损伤具有重要意义.笔者主要从热环境的定义、热环境对人体主要功能系统影响的机制、热应激的影响因素及防护研究进展进行综述,为高温作业人员对热致疾病的认识及防护提供参考.     

急性淋巴细胞白血病患者院内感染风险与营养指标的相关性分析

目的 分析急性淋巴细胞白血病患者(ALL)院内感染风险与营养指标的相关性。方法 选择2018年6月～2021年6月海南医学院第一附属医院住院治疗的124例ALL患者,根据患者是否发生院内感染分为感染组(42例)和未感染组(82例)。给予所有患者支持治疗,收集所有患者一般资料,包括年龄、性别、身体质量指数(BMI)、免疫分型、住院时间、是否使用糖皮质激素、融合基因、有无皮肤黏膜损害等;采用患者主观整体评估评分(PG-SGA评分)评估患者的营养状况;检测患者血清血红蛋白(Hb)、白蛋白(Alb)水平及外周血白细胞计数。以受试者工作特征曲线ROC分析Hb、Alb预测ALL患者发生院内感染的价值,以非条件logistic逐步回归分析ALL患者发生院内感染的危险因素。结果 与未感染组相比,感染组BMI <18.5 kg/m²、住院时间> 30 d、中度和重度营养不良、皮肤黏膜损害的患者比例较高,并且感染组Hb、Alb水平较低,差异有统计学意义(P <0.05);经ROC分析,Hb≤70.993 g/L、Alb≤37.295 g/L是ALL患者发生院内感染的...     

成年功能性构音障碍患者辅音错误类型及方式分析

目的 探讨成年功能性构音障碍患者辅音发音错误的特点,为制定语音训练方案提供依据.方法以42例成年功能性构音障碍患者为研究对象,借助计算机语音工作站对患者进行语音评估,对其辅音的发音错误类型及方式进行分析.结果42例成年功能性构音障碍患者主要的辅音发音错误类型为置换、扭曲,其次为脱落.按发音部位,错误辅音依次为舌尖后音(39例,92.86%)、舌尖前音(31例,73.81%)、舌面音(22例,52.38%)、舌根音(19例,45.24%)、舌尖中音(18例,42.86%)、唇齿音(6例,14.29%)及双唇音(6例,14.29%);辅音错误频率由高至低依次为/sh/、/zh/、/ch/、/r/、/z/、/c/、/s/、/q/、/x/、/j/、/g/、/k/、/h/、/t/、/l/、/d/、/f/、/p/.辅音错误方式有:舌前音化(22例,52.38%)、非送气化(12例,28.57%)、侧化构音(12例,28.57%)、辅音脱落(9例21.42%)、舌后音化(8例,19.05%)、舌面音化(4例,9.52%)、双唇音化(4例,9.52%)、唇齿音化(3例,7.14%).结论成年功能性构音障碍患者的辅音发音错误类型主要是置换和扭曲;错误辅音主要为舌尖后音、舌尖前音、舌面音、舌根音、舌尖中音;辅音发音错误方式主要为舌前音化、非送气化、侧化构音、辅音脱落.     

血脂与血管内超声-虚拟组织学评价冠状动脉粥样硬化斑块性质

目的:探讨血脂和血管内超声-虚拟组织(IVUS-VH)学评价急性冠脉综合征(ACS)和稳定性心绞痛(SA)患者冠状动脉粥样硬化斑块性质。方法:对44例ACS患者及22例SA患者行IVUS-VH分析,并对其血清高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、脂蛋白a[LP(a)]进行测定,计算LDL-C/HDL-C比值,分析冠状动脉粥样硬化斑块坏死核心(NC)所占的比例与LP(a)、LDL-C/HDL-C的相关关系。结果:ACS组斑块中NC和钙化组织比例明显高于SA组(t=4.669、9.894,P<0.001),而纤维组织及纤维脂肪组织则明显低于SA组(t=7.184、5.290,P<0.001)。ACS组患者血清LDL-C/HDL-C、LP(a)水平高于SA组患者(t=3.512、19.139,P<0.001)。ACS组患者冠状动脉粥样硬化斑块中NC比例与血清LP(a)水平有显著的相关性(r=0.549,P<0.001)。结论:LP(a)可能代替IVUS-VH帮助了解冠状动脉粥样硬化斑块的性质。