IL-18诱导外周血单个核细胞对Raji细胞的杀伤效应及其机制的实验研究

目的 探讨IL-18诱导PBMC对Raji细胞的杀伤效应及其作用机制。方法 IL-18在体外诱导PBMC后,以MTT法测定其对Raji细胞的杀伤效应。在杀伤活性最大时,以BAS-ELISA法检测培养上清液sFas-L的含量,以流式细胞仪检测PBMC的CD_(16)/CD_(56)、Fas-L、穿孔素、颗粒酶B表达。结果 PBMC在体外经IL-18诱导后,能明显增强其对Raji细胞的杀伤活性,在PBMC经IL-18诱导后的d 4,这种杀伤活性最高。在杀伤活性最高时,PBMC表达CD16/CD_(56)、Fas-L、穿孔素、颗粒酶B的能力明显增加,但培养上清液中sFas-L的含量无明显增加。结论 本实验的结果显示,IL-18能诱导PBMC杀伤细胞的增殖和活化,并使其对Raji细胞杀伤活性增强,这种杀伤机制可能与穿孔素、颗粒酶B和Fas-L的高表达有关。     

Synthesis and evaluation of a 18F‐labeled 4‐phenylpiperidine‐4‐carbonitrile radioligand for σ1 receptor imaging

We report the design and synthesis of several 4‐phenylpiperidine‐4‐carbonitrile derivatives as σ₁ receptor ligands. In vitro radioligand competition binding assays showed that all the ligands exhibited low nanomolar affinity for σ₁ receptors (K_i(σ₁) = 1.22–2.14 nM) and extremely high subtype selectivity (K_i(σ₂) = 830–1710 nM; K_i(σ₂)/K_i(σ₁) = 680–887). [¹⁸F]9 was prepared in 42–46% isolated radiochemical yield, with a radiochemical purity of >99% by HPLC analysis after purification, via nucleophilic ¹⁸F^‐ substitution of the corresponding tosylate precursor. Biodistribution studies in mice demonstrated high initial brain uptakes and high brain‐to‐blood ratios. Administration of SA4503 or haloperidol 5 min prior to injection of [¹⁸F]9 significantly reduced the accumulation of radiotracers in organs known to contain σ₁ receptors. Two radioactive metabolites were observed in the brain at 30 min after radiotracer injection. [¹⁸F]9 may serve as a lead compound to develop suitable radiotracers for σ₁ receptor imaging with positron emission tomography.     

麝香保心丸联合辛伐他汀对冠心病心绞痛患者血清IL-18、VEGF、T-SOD水平的影响

目的研究麝香保心丸联合辛伐他汀对冠心病心绞痛患者血清白细胞介素-18(IL-18)、血管内皮生长因子(VEGF)、总超氧化物歧化酶(T-SOD)水平的影响。方法选择2018年3月—2020年8月医院收治的150例冠心病心绞痛患者为研究对象,分对照组和研究组各75例,对照组患者口服辛伐他汀,研究组在对照组基础上服用麝香保心丸,两组均连续治疗6个月,观察比较两组:(1)治疗后临床疗效及心电图疗效,(2)治疗前后中医证候积分、生化指标[IL-18、VEGF、T-SOD、甘油三酯(TG)、总胆固醇(TC)、髙密度脂蛋白(DHL)、低密度脂蛋白(LDL)、纤维蛋白原]水平、血浆黏度、心绞痛改善情况,(3)不良反应发生情况。结果治疗后,研究组临床治疗总有效率为(82.67%,62/75)和心电图总有效率(89.33%,67/75)明显高于对照组总有效率[54.67%(41/75)、69.33%(52/75)](P<0.05);治疗前,两组中医证候积分、各生化指标水平、血浆黏度、心绞痛积分、持续时间及发作频率比较差异无统计学意义(P>0.05);治疗后,两组患者中医证候积分、IL-8、L...     

Synthesis and Bio‐Evaluation of New 18F‐Labeled Pyridaben Analogs with Improved Stability for Myocardial Perfusion Imaging in Mice

To improve the stability of ¹⁸F‐labeled pyridaben analogs for myocardial perfusion imaging, three new analogs of pyridaben ([¹⁸F]FPTP2, [¹⁸F]FPTP‐P2, and [¹⁸F]FPTP‐P3) were synthesized with ‘side chain’ modifications. The radiolabeled tracers and corresponding non‐radioactive compounds were obtained by substituting tosyl group with ^18/19F. The effect of structure modification on myocardial targeting and physicochemical properties of new tracers were evaluated in vitro and in vivo. The total radiosynthesis time of these tracers was approximately 70–90 min with high decay‐corrected radiochemical yields (36–65%) and good radiochemical purity (> 98%). These lipophilic tracers exhibited obvious improved stability in water. Studies of their biodistribution in normal Kunming mice demonstrated that [¹⁸F]FPTP2 exhibited very high initial heart uptake (39.70 ± 2.81 %ID/g at 2 min after injection) and low background in the liver, blood, and soft tissues. The heart‐to‐liver, heart‐to‐lung, and heart‐to‐blood ratios were 3.59, 19.34, and 67.34 at 15 min postinjection, respectively. Favorable myocardial targeting property and remarkable improvement of stability of [¹⁸F]FPTP2 suggest that the substitution of the phenyl ‘sidechain’ with other non‐phenyl rings has no effect on the myocardial targeting property of ¹⁸F‐labeled pyridaben analogs.     

哮喘患者血浆白细胞介素-18水平测定及其临床意义的研究

目的探讨白细胞介素(IL)-18在支气管哮喘发病机制中的作用。方法收集30例哮喘患者和15名健康对照者的血浆,采用酶联免疫吸附试验(ELISA)检测血浆中IL-18、IL-12和IL-13的水平。结果哮喘组血浆IL-18、IL-13水平明显高于对照组,IL-12水平则显著低于对照组,差异有显著性(P<0.01)。哮喘组IL-18和IL-13呈显著正相关(P<0.05)。结论IL-18可能参与了哮喘的发病过程,它通过调节Th1/Th2的活性及细胞因子的产生,在哮喘的发病过程中发挥作用。     

非小细胞肺癌患者血清中IL-18和IL-33水平检测及其临床意义

目的探讨非小细胞型肺癌患者中IL-18和IL-33水平检测的临床意义。方法选取2012年1月—2013年3月间于该院进行诊治的49例非小细胞型肺癌患者作为研究对象,同时选取50例健康体检者作为对照组,应用ELISA方法检测血清中IL-18和IL-33水平,进行统计学分析。结果非小细胞型肺癌患者血清中IL-18和IL-33水平均显著高于健康对照组[IL-18:(328.3±12.7)ng·L-1vs(131.7±14.2)ng·L-1;IL-33:364(178~537)ng·L-1vs 156(52~193)ng·L-1,P<0.05],且肿瘤恶性程度越高,IL-18和IL-33水平升高越明显,两者与疾病程度均呈正相关(IL-18:r=0.67,P<0.05;IL-33:r=0.71,P<0.05);不同病理类型患者间IL-18和IL-33水平无统计学差异(P>0.05)。结论非小细胞型肺癌患者血清中IL-18和IL-33含量显著高于健康对照者,且与肿瘤分期呈正相关,可作为评估疾病恶性分期与病情进展的潜在指标,为临床治疗提供一定的理论依据。     

慢性乙型肝炎患者血清TGF-β_1、IL-18的检测及临床意义

目的探讨慢性乙型肝炎(CHB)患者血清TGF-β1、IL-18水平的变化及其临床意义。方法采用ELISA法检测49例CHB患者及30例健康成人血清TGF-β1、IL-18水平,并同时检测各项肝功能指标。结果CHB患者血清TGF-β1、IL-18水平均显著高于对照组(P<0.01),且随CHB的严重程度增高而升高:血清TGF-β1、IL-18水平与血清各项肝功能指标呈正相关(P<0.01);HBeAg阴性组血清中TGF-β1水平较HBeAg阳性组明显低(P<0.01),HBeAg阳性组血清中IL-18水平较HBeAg阴性组明显低(P<0.01)。结论CHB患者血清TGF-β1、IL-18水平与肝细胞损伤指标呈正相关,这对于了解肝组织炎症活动及肝细胞损伤程度具有重要意义,联合检测TGF-β1及IL-18水平有助于肝脏炎症病变的诊断和评估。     

18F-氟代脱氧葡萄糖诱导MCF-7细胞株的凋亡研究

目的研究18F-氟代脱氧葡萄糖(18F-FDG)诱导体外培养MCF-7乳腺癌细胞的凋亡情况。方法不同剂量18F-FDG加入体外培养MCF-7乳腺癌细胞中共培养,以γ计数仪测定细胞摄取18F-FDG的量;用流式细胞仪测定细胞早期和晚期凋亡率;用TUNEL法测定细胞凋亡的数量。结果①相同数量级的MCF-7细胞对18F-FDG的摄取量与剂量增加呈线性;②流式细胞结果示:经12 h18F-FDG孵育引起MCF-7的平均早期凋亡率为12.5%,平均晚期凋亡率为39.3%,总平均凋亡率为51.8%。经24 h18F-FDG孵育引起MCF-7的平均早期凋亡率为10.4%,平均晚期凋亡率为42.1%,总平均凋亡率为52.5%;③TUNEL显示:用凋亡指数(apoptotic index,AI)表示,与空白对照组AI(5.13±1.51)%相比,18F-FDG孵育12 h爬片的AI为(45.93±1.51)%,18F-FDG孵育24 h爬片的AI为(46.93±1.52)%。结论一定剂量范围内,18F-FDG对MCF-7细胞诱导凋亡效果显著。     

抗MRSA海绵真菌的分离及菌株W0707的鉴定

目的对采自海南、湛江海域的海绵样品进行真菌选择性分离,对其发酵液进行抗MRSA活性筛选,并对活性较好的菌株进行鉴定。方法以耐甲氧西林金黄色葡萄球菌MRSA3558为指示菌,利用KB法进行活性菌株筛选,通过对菌株的培养特征、形态特征、18S rDNA序列测定及其系统发育分析对菌株W0707进行鉴定。结果与结论添加青霉素和链霉素的海水马丁氏培养基具有很好的培养真菌选择性,共分离得到真菌133株,活性筛选得到阳性菌株4株,其中菌株W0707具有较强的抗MRSA活性,通过各种指标鉴定菌株W0707为土曲霉(Aspergillus terreus)。