The effect of cholate on solubilisation and permeability of simple and protein-loaded phosphatidylcholine/sodium cholate mixed aggregates designed to mediate transdermal delivery of macromolecules.

Carriers for non-invasive administration of biologically important antioxidant enzymes Cu,Zn-superoxide dismutase (SOD) and catalase (CAT) were developed. Solubilisation and permeabilities of various soybean phosphatidylcholine/sodium cholate (SPC/NaChol) mixtures, mainly in the form of lipid bilayers, focussing on system properties relevant for non-invasive enzyme delivery were investigated in this work. Static and dynamic light scattering measurements gave information on the behaviour of the systems containing up to 40 mM NaChol and 30.6-1.2 mM SPC in the final suspension. The average size of such mixed aggregates was in the 100-200 nm range. Suspension turbidity decreased by 50% upon increasing nominal molar detergent/lipid ratio to NaChol/SPC = 7 and 1.25, in case of SPC = 1.2 and 19.6 mM, respectively. The effective NaChol/SPC molar ratio in bilayers saturated with the detergent was found to be: R(e)(sat) = 0.70 +/- 0.01; bilayer solubilisation point corresponded to R(e)(sol) = 0.97 +/- 0.02, independently of enzyme loading. Vesicles became very permeable to SOD when membrane bound NaChol concentration exceeded 13.7 mM, in case of total starting lipid concentration of 138 mM diluted to SPC = 19.6 mM. Specifically, we measured a 50% loss of SOD from the vesicles with an aggregate-associated molar detergent ratio NaChol/SPC approximately 0.7, which is near the saturation but well below the solubilisation limit. Calcein efflux from such vesicles was compared with SPC/NaChol/SOD mixed aggregates. Our results should contribute to the future design of vesicle mediated transdermal delivery of antioxidant enzymes.     

气道压力释放通气对急性呼吸窘迫综合征患者呼吸机相关性肺损伤的影响

目的 通过测定机械通气对急性呼吸窘迫综合征（Acute Respiratory Distress Syndrome,ARDS）患者支气管肺泡灌洗液（BronchoAlveolar Lavage Fluid,BALF）与血清中肺损伤标记物的变化,明确气道压力释放通气（Airway Pressure Release Ventilation,APRV）与小潮气量保护性通气（Low Tidal Volume Protective Ventilation,LTV）对ARDS患者呼吸机相关性肺损伤（Ventilator-Induced Lung Injury,VILI）的影响。方法 收集深圳大学总医院及海南省人民医院2018-01至2019-05内ARDS住院患者40例,以随机数字法分为两组：A组21例,B组19例,A组先予APRV通气24 h,随后转为LTV 24 h;B组先予LTV 24 h,再转为APRV 24 h,比较干预治疗0 h、24 h、48 h两组患者氧合指数、呼吸力学、BALF及血清中肺泡表面活性蛋白（Pulmonary Surfactant Protein D,SP-D）、重组...     

Target nursing care on anxiety and depression in patients with gallbladder cancer during perioperative period

Background:This study retrospectively investigated the effects of target nursing care (TNC) on anxiety and depression in patients with gallbladder cancer (GBC) during the perioperative period.Methods:This retrospective study analyzed the data of 80 patients with GBC during perioperative period. These records were divided into an intervention group (n = 40) or a control group (n = 40). All 80 patient records in both groups were administered routine nursing care (RNC). The patients in the intervention group also underwent TNC. The primary outcomes were depression (measured using the Hamilton Depression Scale, HAMD) and anxiety (assessed using the Hamilton Anxiety Scale, HAMA). The secondary outcomes were quality of life (assessed using the 36-Item Short Form Health Survey, SF-36) and adverse events. We collected and analyzed the outcome data before and after treatment.Results:After treatment, patients in the intervention group showed more promising effects on depression (HAMD, P < .01) and anxiety (HAMA, P < .01) than those in the control group did. However, there were no significant differences in the quality of life before and after treatment. No TNC- or RNC-associated adverse events were reported in patient records.Conclusion:This study found that TNC was more effective than RNC in relieving depression and anxiety. Future studies should be conducted to validate the present findings.     

Antibacterial activity and inhibition against Staphylococcus aureus NorA efflux pump by ferulic acid and its esterified derivatives

Objective: To evaluate the inhibitory activity of ferulic acid and four of its esterified derivatives (methyl, ethyl, propyl, and butyl) against resistance mech...     

ROC曲线评价尿微量白蛋白和血清Cystatin C在2型糖尿病早期肾损伤中的诊断价值

目的 应用ROC曲线(relative operating characteristic)评价尿微量白蛋白(mAlb)及Cystatin C在糖尿病肾病的早期诊断价值.方法 对152例尿常规检查蛋白阴性的糖尿病患者应用单光子发射计算机断层摄影显像技术行肾动态显像和肾小球滤过率检查,并与尿微量白蛋白及Cystatin C行ROC分析.结果 Cystatin C临界点取1.3 mg/L时ROC曲线下面积0.893,敏感性78.26%,特异性84.9%,阳性似然比5.17,阴性似然比0.52,Youden指数0.736,比数积52.41.尿微量白蛋白临界点取15.6 mg/L时,ROC曲线下面积0.681,敏感性60.87%,特异性79.2%,阳性似然比3.23,阴性似然比0.27,Youden指数0.564,比数积46.38.结论 血清Cystatin C较尿微量白蛋白在2型糖尿病肾病早期损伤诊断中有更好的灵敏性和特异性.     

Vitamin D Enhances Neutrophil Generation and Function in Zebrafish (Danio rerio)

Vitamin D (VD) is a major regulator of calcium metabolism in many living organisms. In addition, VD plays a key role in regulating innate and adaptive immunity in vertebrates. Neutrophils constitute an important part of the first line of defense against invading microbes; however, the potential effect of VD on neutrophils remains elusive. Thus, in this study zebrafish in different developmental stages were utilized to identify the potential role of VD in the basal homeostasis and functions of neutrophils. Our results showed that addition of exogenous VD₃ promoted granulopoiesis in zebrafish larvae. Reciprocally, neutrophil abundance in the intestine of adult zebrafish with a cyp2r1 mutant, lacking the capacity to 25-hydroxylate VD, was reduced. Moreover, VD-mediated granulopoiesis was still observed in gnotobiotic zebrafish larvae, indicating that VD regulates neutrophil generation independent of the microbiota during early development. In contrast, VD was incapable to influence granulopoiesis in adult zebrafish when the commensal bacteria were depleted by antibiotic treatment, suggesting that VD might modulate neutrophil activity via different mechanisms depending on the developmental stage. In addition, we found that VD₃ augmented the expression of il-8 and neutrophil recruitment to the site of caudal fin amputation. Finally, VD₃ treatment significantly decreased bacterial counts and mortality in zebrafish infected with Edwardsiella tarda (E. tarda) in a neutrophil-dependent manner. Combined, these findings demonstrate that VD regulates granulopoiesis and neutrophil function in zebrafish immunity.     

抑制Blimp-1表达导致浆细胞去分化

目的探讨转录因子Bhmp-1在浆细胞发育中的作用。方法应用慢病毒载体稳定表达针对Blimp-1的siRNA,抑制骨髓瘤细胞J558L中Blimp-1的表达。采用免疫荧光及流式细胞技术观察Blimp-1抑制前后细胞的免疫表型变化,半定量RT-PCR检测XBP-1、J-chain、c-myc、BCMA的变化。结果Blimp-1抑制后,浆细胞表面标志CD138表达显著下降,B淋巴细胞免疫标志CD19表达增加。同时,与浆细胞功能及存活密切相关的XBP-1、J-chain、BCMA基因表达下降,而促进B淋巴细胞增殖发育的c-myc表达上升。结论浆细胞中Blimp-1被抑制后,浆细胞发育程序出现再编程,发生了去分化现象,返回到更早期的发育阶段,提示Blimp-1特异性shRNA有可能用于浆细胞相关疾病的治疗。     

中药临床试验安慰剂制作探讨

中药安慰剂对照临床试验在中医临床试验中日益受到重视,但其制作研究仍相对薄弱。中药安慰剂的制作需要根据具体的临床试验设计、研究疾病的性质、试验药物的特点、服药方法等综合考虑,选择适当的工艺流程。其辅料的选择应以无明显偏性的粮食类为佳,在确保安慰剂潜在的药理活性能被专家接受基础上,如果难以做到与试验药物外观及口味一致,应当尽量使之类似于相同剂型的中药。     

苏州产淡水珍珠生物活性评价及镇静活性物质基础研究

目的对苏州产淡水珍珠的镇静、养阴、抗氧化及酪氨酸酶抑制等生物活性进行评价,并针对其镇静活性的物质基础开展研究。方法采用小鼠在黑箱中自发活动计数的方法考察其镇静作用;利用Sephadex G-100对珍珠热提液进行分离,并评价不同相对分子质量段部位的镇静活性,探讨镇静活性的物质基础。建立甲状腺素小鼠阴虚模型考察养阴作用;通过使用改进的邻苯三酚自氧化法及测定SOD、MDA含量考察抗氧化作用。结果珍珠热提液中大、小相对分子质量段部位均有显著的镇静活性;热提液能够明显增强阴虚状态下小鼠的抗疲劳、耐缺氧的能力,有效抑制阴虚状态下各脏器功能的衰减;冷浸液能显著提高小鼠血清SOD含量、降低MDA含量。结论珍珠具有良好的镇静、养阴和抗氧化作用;珍珠的镇静活性源于多组分物质共同作用的结果。