The upregulated intestinal folate transporters direct the uptake of ligand-modified nanoparticles for enhanced oral insulin delivery

Transporters are traditionally considered to transport small molecules rather than large-sized nanoparticles due to their small pores. In this study, we demonstrate that the upregulated intestinal transporter (PCFT), which reaches a maximum of 12.3-fold expression in the intestinal epithelial cells of diabetic rats, mediates the uptake of the folic acid-grafted nanoparticles (FNP). Specifically, the upregulated PCFT could exert its function to mediate the endocytosis of FNP and efficiently stimulate the traverse of FNP across enterocytes by the lysosome-evading pathway, Golgi-targeting pathway and basolateral exocytosis, featuring a high oral insulin bioavailability of 14.4% in the diabetic rats. Conversely, in cells with relatively low PCFT expression, the positive surface charge contributes to the cellular uptake of FNP, and FNP are mainly degraded in the lysosomes. Overall, we emphasize that the upregulated intestinal transporters could direct the uptake of ligand-modified nanoparticles by mediating the endocytosis and intracellular trafficking of ligand-modified nanoparticles via the transporter-mediated pathway. This study may also theoretically provide insightful guidelines for the rational design of transporter-targeted nanoparticles to achieve efficient drug delivery in diverse diseases.     

Corrosion Behavior of Alx(CrFeNi)1−x HEA under Simulated PWR Primary Water

High-entropy alloys (HEAs) have great potential as accident-tolerant fuel (ATF) cladding. Aluminum-forming duplex (BCC and FCC) stainless-steel (ADSS) is a candidate for ATF cladding, but the multiphase composition is detrimental to its corrosion resistance. In this paper, two single-phase HEAs were prepared by adjusting the content of each element in the ADSS alloy. The two HEAs were designed as Al_0.05(CrFeNi)_0.95(FCC) and Al_0.25(FeCrNi)_0.75(BCC). Their corrosion behavior under simulated pressurized water reactor (PWR) primary water was investigated. The corrosion products and corrosion mechanisms of these two HEAs were explored. The results show that the corrosion resistance of HEA alloys containing FCC is better than that of BCC and ADSS alloys. At the same time, the reason why the BCC structure composed of these four elements is not resistant to corrosion is revealed.     

老年患者肺部感染抗菌药物应用分析

目的探讨老年患者肺部感染抗菌药物的合理应用。方法采用回顾性调查方法,对120例老年患者肺部感染抗菌药物使用的合理性进行统计分析。结果15例革兰阳性(G+)球菌感染,主要应用阿奇霉素磷酸二氢钠、阿莫西林克拉维酸钾进行治疗;18例G+球菌、革兰阴性(G-)球菌、G-杆菌混合感染,主要给予加替沙星氯化钠注射液治疗;6例G+球菌、G-球菌混合感染;G+球菌支原体混合感染6例,应用阿莫西林克拉维酸钾治疗;15例支原体感染,主要应用阿莫西林克拉维酸钾、阿奇霉素磷酸二氢钠治疗;42例未检出致病菌,未作病原学检测18例。在收集的病例中,哌拉西林钠舒巴坦钠、加替沙星注射液为主要应用药物。结论老年患者基础疾病较多,肺部感染以混合病原菌感染多见。药物治疗多给予阿莫西林克拉维酸钾、阿奇霉素磷酸二氢钠、加替沙星氯化钠注射液、哌拉西林钠舒巴坦钠等抗菌药物。合理应用抗菌药物,应从药物敏感性试验和合理联用等方面加强,以减少耐药性和药物不良反应的发生。     

Optimization of photo-biomodulation therapy for wound healing of diabetic foot ulcers in vitro and in vivo

Unclear optical parameters make photo-biomodulation (PBM) difficult to implement in diabetic foot ulcer (DFU) clinically. Here, 12 wavelengths (400–900 nm) were used to conduct PBM to heal DFU wounds in vitro and in vivo. PBM at 10 mW/cm² and 0.5–4 J/cm² with all 12 wavelengths promoted proliferation of diabetic wound cells. In a mimic DFU (mDFU) rat model, PBM (425, 630, 730, and 850 nm, and a combination light strategy) promoted mDFU healing. The positive cell proliferation, re-epithelialization, angiogenesis, collagen synthesis, and inflammation were possible mechanisms. The combination strategy had the best effect, which can be applied clinically.     

乙型肝炎与肾素—血管紧张素—醛固酮系统的关系

作者用放射免疫法测定了30例(68例次)乙型肝炎(乙肝)患者和35名正常人的血浆血管紧张素Ⅱ(AT Ⅱ)水平。结果表明,30例乙肝患者AT Ⅱ明显高于35名正常人;各型乙肝患者AT Ⅱ升高值与病情轻重一致,8例肝肾综合征(HRS)患者ATⅡ显著高于未并发HRS者。用巯甲丙脯酸(CPT)治疗后,ATⅡ明显下降,肾功能改善。提示AT Ⅱ升高可能是HRS发生的原因之一,CPT可能抑制了ATⅡ的产生,对HRS有一定疗效。     

趋化因子BLC表达载体构建及在肿瘤细胞中的表达

目的 建立真核表达重组体pcDNA-BLC的稳定转染细胞株,为研究趋化因子BLC的抗肿瘤免疫作用机制奠定基础。方法 以小鼠脾脏组织总RNA为模板,通过RT-PCR扩增BLC全长cDNA,并将扩增的cDNA片段插入pcDNA3．1( )真核表达质粒,构建重组质粒pcDNA-BLC,重组子经限制性内切酶酶切分析及测序鉴定后,用脂质体转染技术导入Colon26细胞,经G418筛选建立稳定转染细胞株。用免疫印迹法(Western Blot)鉴定转染细胞表达的蛋白质,证实BLC存在。用趋化实验证实转染细胞株表达的BLC有生物学活性。结果 真核表达重组体pcDNA-BLC构建成功,pcDNA-BLC稳定转染细胞株表达有生物学活性的BLC。结论 成功建立了BLC的稳定转染细胞株,为研究BLC的抗肿瘤免疫作用机制继而发展肿瘤疫苗奠定了基础。     

咪达唑仑复合输注瑞芬太尼用于老年患者结肠镜检查的效果观察

目的对咪达唑仑复合瑞芬太尼麻醉方法在老年结肠镜检查患者中的应用进行分析研究。方法将我院接受结肠镜检查的老年患者分为两组,分别接受咪达唑仑复合瑞芬太尼麻醉（M组）和异氟烷复合瑞芬太尼麻醉（E组）,比较两组的麻醉效果。结果 M组的血气指标与E组之间存在明显差异,P〈0.05。结论咪达唑仑复合输注瑞芬太尼麻醉方法在老年结肠镜检查患者中的应用是可行的,对患者的血气运行影响较小,值得临床应用。     

人正常卵巢及卵巢癌腺苷酸环化酶活性研究

以人正常卵巢皮质层及手术切除的卵巢癌组织为材料,分别分离纯化细胞膜,测定膜蛋白的腺苷酸环化酶(AC)活性。结果:正常卵巢细胞膜AC活性为67±8U/mg蛋白;卵巢癌细胞膜AC活性明显高于正常,平均活性为234±86U/mg蛋白;卵巢癌中粘液性囊腺癌细胞膜AC活性高于浆液性囊腺癌者。     

Increased expression of receptor activator of nuclear factor-κB ligand in osteoblasts from adolescent idiopathic scoliosis patients with low bone mineral density

Persistent generalized low bone mineral density (BMD) has been reported in patients with adolescent idiopathic scoliosis (AIS).However,the exact mechanisms and causes of the low BMD in AIS patients are largely unknown.The purpose of this study was to examine the relationship between the receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) levels in osteoblasts (OBs) from AIS patients with low BMD and with comparison made between the patients and controls.Twenty AIS patients and eight age-matched controls were included in the present study.The BMD of lumbar spine and proximal femur was measured in all subjects.OBs from the cancellous bone of each subject was harvested and primarily cultured.The mRNA and protein expression of RANKL and OPG in OBs was detected by RT-PCR and Western blotting.The results showed BMD was lower in AIS patients than in controls.A significantly higher mRNA and protein expression of RANKL was observed in OBs from AIS patients,while no significant difference was found in the expression of OPG between AIS patients and controls.As a result,RANKL/OPG ratio in patients with AIS was remarkably higher than controls.Our study preliminarily demonstrated expression of RANKL was higher in OBs from AIS patients with low BMD as compared with controls,suggesting the unbalanced RANKL/OPG ratio caused by an over-expression of RANKL in OBs may be responsible for the low BMD in AIS patients.