粒细胞巨噬细胞刺激因子联合全肺灌洗对特发性肺泡蛋白沉积症的疗效和安全性

目的 观察粒细胞巨噬细胞刺激因子（GM-CSF）联合全肺灌洗治疗特发性肺泡蛋白沉积症（IPAP）的疗效和安全性。方法 选取2015年8月至2017年3月在第二军医大学附属长海医院就诊的2例IPAP患者,经全肺灌洗后,分别予皮下注射和雾化吸入GM-CSF治疗,观察其疗效和安全性。结果 2例患者经GM-CSF联合全肺灌洗治疗,病情缓解。结论 GM-CSF联合全肺灌洗治疗对IPAP患者治疗有效、用药安全。     

注射用重组人血清白蛋白-人粒细胞集落刺激因子(Ⅰ)融合蛋白在健康受试者的耐受性研究

目的评价重组(酵母分泌型)人血清白蛋白-人粒细胞集落刺激因子(Ⅰ)融合蛋白在健康受试者的耐受性和安全性。方法将26例健康受试者(男女各半)按先后顺序入组,进行4个剂量组试验(150,300,500,650μg·kg^-1),每组分别入组4,6,8,8例。根据体重计算给药剂量,受试者于给药当天上臂三角肌部位皮下注射给药1次。用药后观察药物不良事件(AE),定时进行实验室检查、心电图检查。结果共25例受试者发生AE,共145例次。150,300,500及650μg·kg^-1剂量组的AE分别为13,11,56和65例次。其中134例次考虑与研究药物相关。常见的AE有骨痛、单核细胞计数升高、血碱性磷酸酶升高、头痛、高尿酸血症、血乳酸脱氢酶升高、脾肿大、肌肉疲劳。研究中未出现AE导致的用药暂停、受试者退出或试验提前中止。未发生严重不良事件(SAE)。未发生剂量限制性毒性。结论注射用重组(酵母分泌型)人血清白蛋白-人粒细胞集落刺激因子(Ⅰ)融合蛋白在中国健康受试者中单次给药150,650μg·kg^-1剂量范围内有较好的安全性,本临床试验未探索到健康人群的最大耐受剂量。     

眼用即型凝胶的现状与研究进展简

眼用即型凝胶避免了传统眼用制剂滞留时间短、消除速度快、生物利用度低等缺点,可以增强眼用制剂的药效,近年来倍受研究者的关注.本文介绍了眼用即型凝胶的分类及其不同成胶机制,综述了其在国内外的研究进展和上市产品.作为一种新型制剂,虽然眼用即型凝胶在国内的研究尚处于起步阶段,但其具有广阔的临床应用前景,值得进一步研究开发.     

神阙灸防治ICU肠内营养并发腹泻的临床疗效观察

目的：观察艾灸神阙穴防治ICU肠内营养并发腹泻的临床疗效。方法将120例患者随机分为试验组和对照组,每组60例,所有患者在积极治疗原发疾病同时,给予百普力采用持续输注的鼻饲方式进行肠内营养,试验组在肠内营养第1天开始给予神阙穴温和灸。结果在肠内营养治疗第7天时观察患者的腹泻发生率,发现试验组、对照组腹泻发生率分别为16.7%、36.7%,试验组明显低于对照组,经x2检验,P＜0.05,差异有统计学意义。结论神阙穴艾灸用于防治ICU危重患者肠内营养并发的腹泻疗效显著,且操作简便,成本低廉,值得推广应用。     

正交试验法优选复方当益颗粒成型工艺简

目的优选复方当益颗粒的最佳成型工艺。方法以颗粒的成型性、溶解性、吸湿性和流动性为考察指标,用La（34）正交试验优选成型工艺。结果最佳成型工艺为采用糊精作为稀释剂,水为润湿剂,混合粉末与润湿剂用量比为10：4.5。结论该工艺合理可行,稳定可靠,可为生产提供依据。     

Designing the epitope flanking regions for optimal generation of CTL epitopes

The flanking amino acids that surround epitopes are critical for effective antigen processing and maintenance of epitope integrity. In the present study, the frequency and characteristics of each amino acid that flanked the peptides generated from the proteasomal degradation of three different subtypes of HIV-1 Gag-p24 were determined. Synthetic flanking regions were designed based on the highest and the lowest frequencies of amino acid with the ideal characteristics at positions upstream and downstream of the proteasomal cleavage site. Peptides were synthesized that contained known CD8+ CTL-epitopes from HIV-1 Gag, CMV pp65, and vaccinia proteins HRP-2, and C16, flanked by amino acid sequences specifically designed to either generate or inhibit the known CD8+ CTL-epitopes. As predicted, the known CD8+ CTL-epitopes were effectively generated from the peptides with synthetic flanking regions specifically designed to promote epitope generation in a proteasome-dependent manner. The majority of the proteasome-generated epitopes were cleaved immediately after the C-terminal amino acid of the specific CTL-epitope. The synthetic peptide sequences containing known CD8+ CTL-epitopes with the flanking regions that promote epitope generation were effectively processed and presented to epitope specific CD8+ T-cells resulting in the production of IFN-γ. These results highlight the importance of flanking regions in promoting efficient antigen processing and presentation. This concept can have important implications in vaccine design and development strategies.     

Lonicerin targets EZH2 to alleviate ulcerative colitis by autophagy-mediated NLRP3 inflammasome inactivation

Aberrant activation of NLRP3 inflammasome in colonic macrophages strongly associates with the occurrence and progression of ulcerative colitis. Although targeting NLRP3 inflammasome has been considered to be a potential therapy, the underlying mechanism through which pathway the intestinal inflammation is modulated remains controversial. By focusing on the flavonoid lonicerin, one of the most abundant constituents existed in a long historical anti-inflammatory and anti-infectious herb Lonicera japonica Thunb., here we report its therapeutic effect on intestinal inflammation by binding directly to enhancer of zeste homolog 2 (EZH2) histone methyltransferase. EZH2-mediated modification of H3K27me3 promotes the expression of autophagy-related protein 5, which in turn leads to enhanced autophagy and accelerates autolysosome-mediated NLRP3 degradation. Mutations of EZH2 residues (His129 and Arg685) indicated by the dynamic simulation study have found to greatly diminish the protective effect of lonicerin. More importantly, in vivo studies verify that lonicerin dose-dependently disrupts the NLRP3–ASC–pro-caspase-1 complex assembly and alleviates colitis, which is compromised by administration of EZH2 overexpression plasmid. Thus, these findings together put forth the stage for further considering lonicerin as an anti-inflammatory epigenetic agent and suggesting EZH2/ATG5/NLRP3 axis may serve as a novel strategy to prevent ulcerative colitis as well as other inflammatory diseases.     

Identification of potential therapeutic target of naringenin in breast cancer stem cells inhibition by bioinformatics and in vitro studies

Cancer therapy is a strategic measure in inhibiting breast cancer stem cell (BCSC) pathways. Naringenin, a citrus flavonoid, was found to increase breast cancer cells’ sensitivity to chemotherapeutic agents. Bioinformatics study and 3D tumorsphere in vitro modeling in breast cancer (mammosphere) were used in this study, which aims to explore the potential therapeutic targets of naringenin (PTTNs) in inhibiting BCSCs. Bioinformatic analyses identified direct target proteins (DTPs), indirect target proteins (ITPs), naringenin-mediated proteins (NMPs), BCSC regulatory genes, and PTTNs. The PTTNs were further analyzed for gene ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein–protein interaction (PPI) networks, and hub protein selection. Mammospheres were cultured in serum-free media. The effects of naringenin were measured by MTT-based cytotoxicity, mammosphere forming potential (MFP), colony formation, scratch wound-healing assay, and flow cytometry-based cell cycle analyses and apoptosis assays. Gene expression analysis was performed using real-time quantitative polymerase chain reaction (q-RT PCR). Bioinformatics analysis revealed p53 and estrogen receptor alpha (ERα) as PTTNs, and KEGG pathway enrichment analysis revealed that TGF-ß and Wnt/ß-catenin pathways are regulated by PTTNs. Naringenin demonstrated cytotoxicity and inhibited mammosphere and colony formation, migration, and epithelial to mesenchymal transition in the mammosphere. The mRNA of tumor suppressors P53 and ERα were downregulated in the mammosphere, but were significantly upregulated upon naringenin treatment. By modulating the P53 and ERα mRNA, naringenin has the potential of inhibiting BCSCs. Further studies on the molecular mechanism and formulation of naringenin in BCSCs would be beneficial for its development as a BCSC-targeting drug.     

国产重组人粒细胞集落刺激因子在妇科恶性肿瘤化疗中的应用

目的:探讨不同剂量国产重组人粒细胞集落刺激因子(rhG-CSF)在妇科恶性肿瘤化疗中的疗效,并与进口rhG-CSF比较。方法:98例卵巢癌、宫体癌和宫颈癌患者随机分成3组,分别按75μg·d-1和150μg·d-1剂量皮下注射国产rhG-CSF和进口75μg·d-1 rhG-CSF,直到白细胞或中性粒细胞绝对数升至正常水平以上。结果:不同剂量国产或进口rhG-CSF均能使3组患者血WBC和ANC水平在用药d 4后升至正常水平以上;在初次化疗时,用不同剂量(75μg和150μ)国产和进口(75μg)rhG-CSF升WBC至正常水平的天数无显著差异(P>0.05),但重复化疗期间150μg国产,rhG-CSF升白细胞的疗效显著优于75μg国产或进口rhG-CSF;同等剂量国产rhG-CSF与进口rhG-CSF升WBC效果一致。结论:75μg小剂量国产rhG-CSF在妇科恶性肿瘤初期化疗中升WBC的疗效肯定,重复化疗时较大剂量(150μg)rhG-CSF升WBC的效果优于小剂量rhG-CSF。同等剂量国产rhG-CSF与进口rhG-CSF的疗效无明显差异。