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【国家自然科学基金】_第三军医大学_基金支持热词逐年推荐_【万方软件创新助手】_20140802

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3_种常用碳青霉烯类抗生素血药浓度UPLC-MS

3种常用碳青霉烯类抗生素血药浓度UPLC-MS/MS检测方法的建立Δ秦怡1＊，张瑞霞2，吕雅瑶2，翁莉莉1，张弋2 #（1.天津医科大学一中心临床学院，天津　300192；2.天津市第一中心医院药学部，天津　300192）中图分类号 R917；R978.1文献标志码 A 文章编号 1001-0408（2024）03-0343-05DOI 10.6039/j.issn.1001-0408.2024.03.14摘要目的建立3种临床常用碳青霉烯类抗生素——厄他培南（ETP）、亚胺培南（IPM）、美罗培南（MEM）血药浓度检测的超高效液相色谱-质谱联用（UPLC-MS/MS）法。

方法血浆样品经甲醇沉淀蛋白后，以3种抗生素的稳定性同位素（ETP-D4、IPM-D4、MEM-D6）为内标，采用ACQUITY UPLC BEH C18（2.1 mm×50 mm，1.7μm）色谱柱分离；流动相为98%乙腈+2%水+0.1%甲酸和98%水+2%乙腈+0.1%甲酸，梯度洗脱；流速为0.3 mL/min；柱温为40 ℃；采用正离子、多反应监测模式进行扫描分析。

结果该方法专属性良好，在ETP、IPM、MEM 0.2～200、0.1～100、0.1～100μg/mL范围内线性良好（r2≥0.993），批内、批间精密度和准确度良好（RE均≤5.14%，RSD均≤11.15%），基质效应、提取回收率较一致（RSD≤12.99%）。

结论本实验建立了一种可以同时定量ETP、IPM、MEM血药浓度的UPLC-MS/MS法，该方法样品前处理简单、检测时间短、所需样品量少，可满足临床需求。

关键词碳青霉烯类抗生素；超高效液相色谱-质谱联用；血药浓度；厄他培南；亚胺培南；美罗培南Establishment of UPLC-MS/MS method for the determination of plasma concentration of three common carbapenem antibioticsQIN　Yi1，ZHANG　Ruixia2，LYU　Yayao2，WENG　Lili1，ZHANG　Yi2（1. First Central Clinical College of Tianjin Medical University，Tianjin 300192，China；2. Dept. of Pharmacy，Tianjin First Central Clinical Hospital，Tianjin 300192， China）ABSTRACT OBJECTIVE To establish a UPLC-MS/MS method for the determination of plasma concentration of three carbapenem antibiotics，i.e. ertapenem （ETP），imipenem （IPM）and meropenem （MEM）.METHODS After protein precipitation with methanol，the plasma samples were separated by ACQUITY UPLC BEH C18column （2.1mm×50mm，1.7μm）using stable isotopes of three antibiotics （ETP-D4，IPM-D4，MEM-D6）as the internal standard. The mobile phases were 98%acetonitrile +2% water +0.1%formic acid and 98%water +2%acetonitrile +0.1%formic acid，by gradient elution. The flow rate was 0.3mL/min and the column temperature was 40 ℃. Scanning analysis was performed in the positive ion and multiple reaction monitoring mode. RESULTS The method had good specificity，good linearity （r2≥0.993）in the range of 0.2-200，0.1-100and 0.1-100μg/mL of ETP，IPM and MEM，and good intra-batch and inter-batch precision and accuracy （all RE≤5.14%，all RSD≤11.15%），the matrix effect and extraction recovery were consistent （RSD≤12.99%）. CONCLUSIONS This study establishes the UPLC-MS/MS method to simultaneously quantify the plasma concentration of ETP，IPM and MEM. The method has the advantages of simple pretreatment， short detection time and small sample quantity to meet clinical requirement.KEYWORDS carbapenem antibiotics； UPLC-MS/MS； plasma concentration； ertapenem； imipenem； meropenem碳青霉烯类抗生素具有抗菌谱广、抗菌活性强、耐药率低的特点，已成为治疗重症感染的主要选择。

氯化钴诱导hiPSC-CMs体外缺氧模型的建立

浙江理工大学学报，2021,45(1)：84-93Journal of Zhejiang Sci-Tech UniversityDOI：10.3969力.issn.l673-3851(n),2021.01.011氯化钻诱导hiPSC-CMs体外缺氧模型的建立朱梦怡-柯敏霞I,王皓齐念民益3,吴月红(1.浙江理工大学生命科学与医药学院，杭州310018；2.杭州标模生物科技有限公司，杭州310018；3.上海丽坤生物科技股份有限公司，上海201499)摘要：为进一步了解缺氧性心血管疾病的发病机制.通过使用CHIR99021和IWP2抑制剂的组合诱导和单层诱导分化方法获得人诱导性多能干细胞来源心肌细胞(Human induced pluripotent stem cells-derived cardiomyocytes,hiPSC-CMs).并在hiPSC-CMs的培养系统中加入氯化祐进行处理，通过CCK-8检测,Hoechst荧光染色分析、台盼蓝染色分析、qRT-PCR检测和Western blot检测确定最佳处理浓度和时间。

CCK-8检测结果显示，低浓度CoCl2(100,300M mol/L)处理显著提高hiPSC-CMs细胞活力(/><0.01),高浓度CoCl2(900,1200M mol/L)处理显著抑制hiPSC-CMs细胞活力(p<0.001).并且作用趋势呈剂量和时间依赖性，600M mol/L CoCl2处理对于hiPSC-CMs的细胞活力影响不明显(/><0.05)；Hoechst荧光染色结果显示,CoCl2处理24h和48h后，低浓度CoCl2处理对细胞无影响，Hoechst染色阳性细胞数量少(p>0.05),高浓度CoCl2处理剂量依赖性增加阳性细胞数量(^<0.0001),且48h处理组的结果与24h处理组无显著差异；台盼蓝染色结果表明,CoCl2处理可剂量依赖性促进细胞凋亡；CoCl2处理后，促凋亡相关基因Bax和蛋白Bax表达呈剂量依赖性上调(/><0.001),抗凋亡相关基因B4-2和蛋白Bcl-2表达呈剂量依赖性下调(p<0.OODsCoCb处理可剂量依赖性促进hiPSC-CMs细胞的凋亡。

达格列净联合二甲双胍治疗初诊2_型糖尿病的临床疗效分析

达格列净联合二甲双胍治疗初诊2型糖尿病的临床疗效分析卢宁，刘艳梅，仇颖盐城市第一人民医院内分泌科，江苏盐城224000[摘要]目的探讨达格列净联合二甲双胍治疗初诊2型糖尿病患者的临床疗效及其安全性。

方法选取2021年9月—2022年11月在盐城市第一人民医院内分泌科接受治疗的初诊2型糖尿病患者70例为研究对象，根据系统盲选分组法分成两组，每组35例。

对照组应用二甲双胍治疗，观察组应用达格列净+二甲双胍治疗。

检测并对比两组患者血糖指标、血脂指标、体质指数、不良反应发生情况及疗效。

结果治疗后，观察组血糖及血脂各项指标水平均优于对照组，体质指数低于对照组，差异有统计学意义（P<0.05）。

观察组治疗总有效率高于对照组，差异有统计学意义（P<0.05）。

两组不良反应发生率比较，差异无统计学意义（P>0.05）。

结论达格列净联合二甲双胍对初诊2型糖尿病患者具有良好的治疗作用，有助于改善血糖和血脂、体质量水平，不良反应较少。

[关键词] 达格列净；二甲双胍；初诊2型糖尿病；不良反应；治疗效果[中图分类号] R587.1 [文献标识码] A [文章编号] 1672-4062（2023）03（b）-0091-04 Clinical Analysis of Dapagliflozin Combined with Metformin in the Treat⁃ment of Newly Diagnosed Type 2 Diabetes MellitusLU Ning, LIU Yanmei, QIU YingDepartment of Endocrinology, Yancheng First People´s Hospital, Yancheng, Jiangsu Province, 224000 China[Abstract] Objective To investigate the clinical efficacy and safety of Dapagliflozin combined with metformin in the treatment of newly diagnosed type 2 diabetes patients.Methods Seventy newly diagnosed patients with type 2 diabetes who received treatment in the Endocrinology Department of Yancheng First People´s Hospital from September 2021 to November 2022 were selected as the research objects and divided into two groups with 35 cases in each group accord⁃ing to systematic blind selection grouping. The control group was treated with metformin, and the observation group was treated with dagliazine+metformin. Blood glucose index, blood lipid index, body mass index, occurrence of ad⁃verse reactions and efficacy of the two groups were detected and compared.Results After treatment, the blood glucose and lipid levels of the observation group were better than those of the control group, while the body mass index of the observation group was lower than that of the control group, the difference was statistically significant (P<0.05). The to⁃tal effective rate of the observation group was higher than that of the control group, and the difference was statistically significant (P<0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P>0.05).Conclusion Dapagliflozin combined with metformin has a good therapeutic effect on newly diag⁃nosed type 2 diabetes patients, which can help to improve blood glucose, blood fat and body mass level, and less ad⁃verse reactions.[Key words] Dapagliflozin; Metformin; Newly diagnosed type 2 diabetes mellitus; Adverse reaction; Therapeutic effect目前，老年化问题越发突出，加之国民饮食习惯、膳食结构以及饮食偏好的变化，使得糖尿病患者逐渐增多[1]。

维持性血液透析对终末期肾病患者的治疗及临床预后评价

DOI：10.16662/ki.1674-0742.2023.29.052维持性血液透析对终末期肾病患者的治疗及临床预后评价王迎春，杨文杰，张智成仙游博爱医院，福建莆田351200［摘要］目的分析终末期肾病患者接受维持性血液透析的治疗效果、临床预后。

方法随机选取2021年1—12月仙游博爱医院收治的80例终末期肾病患者为研究对象，应用随机数表法分为对照组和观察组，包括对照组40例和观察组40例，均接受维持性血液透析治疗，对照组使用低通量血液透析，观察组使用高通量血液透析。

对比两组疗效及预后。

结果观察组临床总疗效（95.00%）高于对照组（77.50%），差异有统计学意义（χ2=5.164，P<0.05）。

两组血肌酐、尿素氮对比，差异无统计学意义（P>0.05）。

治疗后，观察组血清甲状旁腺激素、β2-微球蛋白水平低于对照组，差异有统计学意义（P<0.05）。

两组血钙水平比较，差异无统计学意义（P>0.05）。

治疗后，观察组血磷水平低于对照组，差异有统计学意义（P<0.05）。

观察组并发症发生率为7.50%，低于对照组，差异有统计学意义（χ2=4.500，P<0.05）。

结论应用维持性血液透析治疗终末期肾病患者的临床疗效良好，特别是与低通量血液透析相比，采取高通量血液透析的治疗方式，可以显著提升患者临床预后，改善各种临床指标，降低并发症发生率。

［关键词］终末期肾病；维持性血液透析；临床疗效；钙磷代谢水平；并发症［中图分类号］R5 ［文献标识码］A ［文章编号］1674-0742（2023）10(b)-0052-04Evaluation of the Treatment and Clinical Prognosis of Patients with End-stage Renal Disease by Maintenance HemodialysisWANG Yingchun, YANG Wenjie, ZHANG ZhichengXianyou Boai Hospital, Putian, Fujian Province, 351200 China[Abstract] Objective To analyze the therapeutic effect and clinical prognosis of patients with end-stage renal disease receiving maintenance hemodialysis. Methods A total of 80 patients with end-stage renal disease admitted to Xianyou Boai Hospital from January 2021 to December 2021 were randomly selected as the study objects and divided into con⁃trol group and observation group by random number table method, including 40 cases in the control group and 40 cases in the observation group, all of whom received maintenance hemodialysis treatment. The control group received low-flux hemodialysis, and the observation group received high-flux hemodialysis. The efficacy and prognosis of the two groups were compared. Results The total clinical efficacy of observation group (95.00%) was higher than that of control group (77.50%), and the difference was statistically significant (χ2=5.164, P<0.05). There was no statistically significant difference in serum creatinine and urea nitrogen between two groups after treatment (P>0.05). After treat⁃ment, the serum parathyroid hormone and β2-microglobulin levels in observation group were lower than those in con⁃trol group, and the difference was statistically significant (P<0.05). There was no statistically significant difference in blood calcium level between two groups (P>0.05), After treatment, the blood phosphorus level of the observation group was lower than that of the control group, and the difference was statistically significant (P<0.05). The complication rate of observation group was 7.50%, which was lower than that of control group, and the difference was statistically signifi⁃cant (χ2=4.500, P<0.05). Conclusion The application of maintenance hemodialysis in the treatment of end-stage renal disease patients has good clinical efficacy, especially compared with low-flux hemodialysis, the adoption of high-flux [作者简介] 王迎春（1981-），女，本科，主治医生，研究方向为血液透析。

加速溶剂萃取-超高效液相色谱-串联质谱法测定大枣中3种五环三萜酸

食品与药品Food and Drug2021年第23卷第1期17加速溶剂萃取-超高效液相色谱-串联质谱法测定大枣中3种五环三祜酸张萍，何婷，王颖，胡克特，顾丁，陈荣祥**(遵义医科大学基础医学院，贵州遵义563000)摘要：目的建立加速溶剂萃取-超高效液相色谱-串联质谱法(ASE-UPLC-MS/MS)同时测定大枣中桦木酸、齐墩果酸和熊果酸的方法。

方法样品釆用ASE提取，优化提取条件，并与超声辅助提取法进行比较。

优化后的提取条件为：以80%甲醇为提取溶剂，提取温度100-C,静态萃取时间15min,萃取1次。

提取液釆用Waters ACQUITY BEH C18色谱柱分离，以乙ffi-15mmol/L乙酸钱(pH9.3)为流动相，梯度洗脱，经UPLC-MSZMS仪，釆用电喷雾电离源，负离子模式下多反应监测模式检测。

结果桦木酸、齐墩果酸、熊果酸在0.5~10 mg/L范围内，浓度与峰面积线性关系良好，相关系数大于0.9900。

不同浓度3种化合物的加标回收率93.6%〜101.7%,相对标准偏差在1.18%~6.83%之间。

结论此法简单快速、准确稳定、重复性好，可用于大枣中桦木酸、齐墩果酸、熊果酸的含量测定。

关键词：加速溶剂萃取；超高效液相色谱；串联质谱法；大枣中图分类号：R284.1文献标识码：A文章编号：1672-979X(2021)01-0017-06DOI：10.3969/j.issn.l672-979X.2021.01.004Simultaneous Determination of Three Pentacyclic Triterpenic Acids in Jujubae Fructus byAccelerated Solvent Extraction-UPLC-MS/MSZHANG Ping,HE Ting,WANG Ying,HU Ke-te,GU Ding,CHEN Rong-xiang(School of B asic Medical Sciences,Zunyi Medical University,Zu^yi563000,China)Abstract:Objective To establish a method for the simultaneous determination of betulinic acid,oleanolic acid and ursolic acid in Jujubae fructus by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)with accelerated solvent extraction(ASE).Methods The extract parameters of A SE were optimized and the efficiency was compared with the ultrasound-assisted extraction method.The optimum extraction conditions were as follows:80%methanol was selected as extraction solvent,oven temperature was100°C,the static extraction time was 15min and one extraction cycle was adopted.A waters ACQUITY BEH C18(2.1mmx]00mn,1.7“m)column was used as the stationary phase,acetonitrile and ammonium acetate solution(15mmol/L,pH9.3)was used as the mobile phase.Mass detection was conducted by electrospray ionization in negative ion multiple reaction monitoring mode. Results The calibration curves were linear over a concentration range of0.5-10mg/L for betulinic acid,oleanolic acid and ursolic acid.The correlation coefficients were greater than0.9900.The recoveries of different spiked levels were between93.6%and101.7%,with RSDs between1.18%and6.83%.Conclusion The method is simple,rapid,收稿日期：2020-09-04基金项目：国家自然科学基金(31660131,81760652)；贵州省联合基金(黔科合J字LKZ[2013]17号)；遵义医学院博士启动基金(F-568)作者简介：张萍，硕士研究生，研究方向：药用植物开发与利用E-mail:******************通讯作者：陈荣祥，教授，博士，研究方向：药用植物开发与利用E-mail:*************************18食品与药品Food and Drug2021年第23卷第1期accurate,stable and reproducible.It can be used for the determination of betulinic acid,oleanolic acid and ursolic acid in Jujubae f ructus.Key Words:accelerated solvent extraction;ultra-high performance liquid chromatography;tandem mass spectrometry; Jujubae f ructus.大枣为鼠李科植物枣树（Ziziphus jujuba Mill.）的干燥成熟果实，不仅作为食物，还是传统中医药中的常用药材。

基于人工智能的冠状动脉易损斑块腔内影像学研究进展

基于人工智能的冠状动脉易损斑块腔内影像学研究进展陈远兴综述韩韦钰，赵然尊审校遵义医科大学附属医院心血管内科，贵州遵义563000【摘要】斑块的不稳定导致冠状动脉的血栓性闭塞是大多数急性冠脉综合征(ACS)的原因。

尽管罪犯血管得以及时开通，但非罪犯血管的易损斑块对患者远期预后仍存在较大威胁。

因此，动态评估易损斑块的变化，对冠心病患者格外重要。

冠状动脉血管腔内成像技术，如血管内超声(IVUS)、光学相干断层扫描(OCT)、近红外光谱(NIRS)以及其多模态融合技术等，因其可视化、准确度高，可以揭示易损斑块的不同特征，常用于检测易损斑块。

而IVUS 、OCT 等图像解释需有经验的心血管临床医生逐帧判断，需要大量的时间成本，且图像的解读存在的观察者内及观察者间的差异，这推动了人工智能(AI)在冠状动脉血管腔内影像学应用的发展。

由于电子医疗系统的广泛应用、临床大数据的日益暴增，AI 已在医疗行业获得了极大的进展。

人工智能结合腔内影像学在斑块的识别、干预、预后等诸多方面广泛应用，未来将不断优化诊疗系统，提高精准医疗水平，实现对易损斑块的早期诊断及合理干预。

【关键词】动脉粥样硬化；急性冠脉综合征；腔内成像；易损斑块；人工智能【中图分类号】R541.4【文献标识码】A【文章编号】1003—6350（2023）03—0445—05Research progress of intravascular imaging of vulnerable coronary plaque based on artificial intelligence.CHEN Yuan-xing,HAN Wei-yu,ZHAO Ran-zun.Department of Cardiovascular Medicine,Affiliated Hospital of Zunyi Medical University,Zunyi 563000,Guizhou,CHINA【Abstract 】Plaque vulnerability leading to thrombotic occlusion of coronary arteries is the main cause of majori-ty of acute coronary syndrome (ACS).Despite the criminal vessels can be opened in time,the vulnerable plaques of non-criminal vessels still cause a great threat to the long-term prognosis of patients.Thus,dynamic assessment of vulner-able plaque changes is particularly important for patients with coronary heart disease.Intravascular imaging techniques in coronary arteries,such as intravascular ultrasound (IVUS),Optical Coherence Tomography (OCT),Near Infrared Spectrum Instrument (NIRS),and its multi-mode fusion technology,are often used to detect vulnerable plaques due to their high visualization and accuracy,which can reveal different characteristics of vulnerable plaques.However,IVUS,OCT and other image interpretation requires experienced cardiovascular clinicians to judge frame by frame,which re-quires a large amount of time cost,and there are intra-observer and inter-observer differences in image interpretation,which all promotes the development of AI in the application of intravascular coronary imaging.Artificial intelligence (AI)has made great progress in the medical field due to the wide application of electronic medical information system and the increasing explosion of clinical big data.Artificial intelligence combined with intravascular imaging has been widely ap-　·综述·doi:10.3969/j.issn.1003-6350.2023.03.035第一作者：陈远兴(1995—)，男，住院医师，主要研究方向为冠状动脉粥样硬化性心脏病腔内影像学图像分析。

细胞程序性死亡配体1表位肽疫苗的设计及抗肿瘤活性

学报Journal of China Pharmaceutical University 2023，54（2）：245 - 254245细胞程序性死亡配体1表位肽疫苗的设计及抗肿瘤活性邵世帅，段树康，田浤，姚文兵，高向东*（中国药科大学生命科学与技术学院江苏省生物药物成药性研究重点实验室，南京 211198）摘要目前已有多款细胞程序性死亡受体1（PD-1）和其配体（PD-L1）免疫检查点阻断抗体用于临床治疗，但只有部分患者表现出临床反应，因此需要一种替代的肿瘤免疫治疗策略。

以PD-L1为靶点的治疗性肿瘤疫苗是一种有意义的尝试。

本研究设计了以PD-L1为靶点的表位肽疫苗，然后基于人源化免疫系统（HIS）小鼠模型筛选，具有免疫原性的PD-L1表位肽，进一步研究其抗肿瘤活性。

结果显示，设计并筛选得到的PD-L1-B1表位肽疫苗不仅成功诱导了PD-L1特异性的体液免疫和细胞免疫，还表现出抗肿瘤活性。

此外，免疫治疗还增加了肿瘤的T淋巴细胞浸润，重塑了肿瘤免疫抑制微环境。

综上所述，PD-L1-B1表位肽疫苗表现出强效的抗肿瘤活性，对PD-1/PD-L1阻断不敏感的患者可能是一种有效的替代免疫治疗策略。

关键词肿瘤免疫；免疫检查点；PD-L1；表位肽疫苗中图分类号R73-3 文献标志码 A 文章编号1000 -5048（2023）02 -0245 -10doi：10.11665/j.issn.1000 -5048.2023022803引用本文邵世帅，段树康，田浤，等.细胞程序性死亡配体1表位肽疫苗的设计及抗肿瘤活性［J］.中国药科大学学报，2023，54（2）：245–254.Cite this article as：SHAO Shishuai，DUAN Shukang，TIAN Hong，et al. Design and antitumor activity of programmed cell death ligand 1 epitope peptide vaccine［J］.J China Pharm Univ，2023，54（2）：245–254.Design and antitumor activity of programmed cell death ligand 1 epitope peptide vaccineSHAO Shishuai, DUAN Shukang, TIAN Hong, YAO Wenbing, GAO Xiangdong*Jiangsu Provincial Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceu⁃tical University, Nanjing 211198, ChinaAbstract Several programmed cell death protein 1 (PD-1) or its ligand (PD-L1) immune checkpoint blocking antibodies are available for clinical treatment, but only some patients show clinical response, so an alternative strategy for tumor immunotherapy is needed.A therapeutic tumor vaccine targeting PD-L1 is a meaningful attempt.In this study, we designed an epitope peptide vaccine targeting PD-L1, and then screened the immuno‑genic PD-L1 epitope peptide based on the humanized immune system (HIS) mouse model and further investigated its anti-tumor activity.The results show that the designed and screened PD-L1-B1 epitope peptide vaccine not only successfully induced PD-L1-specific humoral and cellular immunity, but also exhibit anti-tumor activity.In addi‑tion, immunotherapy increased T-lymphocyte infiltration of tumors and reshaped the tumor immunosuppressive microenvironment.In conclusion, PD-L1-B1 epitope peptide vaccine exhibits potent anti-tumor activity and may be an effective alternative immunotherapeutic strategy for patients insensitive to PD-1/PD-L1 blockade.Key words tumor immunity; immune checkpoint; PD-L1; epitope peptide vaccineThis study was supported by the National Natural Science Foundation of China (No.82073754, No.81973222); and the Key Research and Development Program of Xinjiang Uygur Autonomous Region (No.2020B03003)收稿日期2023-02-28 *通信作者Tel：134****2857E-mail：1019830864@基金项目国家自然科学基金资助项目（No.82073754，No.81973222）；新疆维吾尔自治区重点研发计划（No.2020B03003）学报 Journal of China Pharmaceutical University 2023，54（2）：245 - 254第54 卷免疫检查点阻断（ICB ）疗法在癌症治疗方面取得了前所未有的进展，极大地改变了肿瘤治疗策略［1-2］。

Keap1

非小细胞肺癌(non-small cell lung cancer，NSCLC)发病率占据肺癌的75%~80%。

肿瘤细胞进展快且易扩散转移，临床常采用手术、放化疗等进行治疗，但5年生存率低于60%[1-2]。

氧化应激是由活性氧(ROS)生成量增加所致，ROS积累可诱导肺癌细胞凋亡，清除ROS 可阻止癌细胞凋亡，即肺癌细胞存活依赖于癌细胞自身抗氧化能力[3]。

Kelch样环氧氯丙烷相关蛋白-1 (kelch-like epichlorohydrin-associated protein-1，Keap1)/核因子E2相关因子2(nuclear factor E2related factor 2，Nrf2)信号通路在癌症中发挥重要调控作用，氧化应激可激活Keap1，促使Keap1-Nrf2复合物裂解，Nrf2转移至细胞核内，可激活下游靶基因表达，参与肺癌发生发展过程[4]。

Nrf2可维持氧化还原稳态，ROS侵袭细胞时，Nrf2可进入细胞核，结合抗氧化反应元件(ARE)转录编码各种抗氧化蛋白、代谢酶基因，抑制氧化应激反应[5-6]。

目前氧化应激、Keap1/Nrf2信号通路在NSCLC发生过程中的机制尚未明确。

基于此，本研究尝试分析Keap1/Nrf2信号通路与临床病理参数、氧化应激指标的相关性，探讨其在NSCLC氧化应激机制中的作用，为临床研制新药提供参考依据。

1资料与方法1.1一般资料选取2017年4月至2020年4月郑州市第三人民医院收治的100例NSCLC患者为研究对象。

纳入标准：符合NSCLC诊断标准[7]；术前未接受放化疗、免疫治疗者；预计生存期≥6个月；符合手术适应证、禁忌证；Karnofsky功能状态评分≥70分；签署知情同意书。

排除标准：合并凝血功能障碍、肝肾功能障碍、其他恶性肿瘤者；伴有急/慢性感染者；伴有精神疾病者；既往腹部相关外科手术史者。

所有患者均行肺癌根治性切除术，术中收集癌组织、癌旁组织(距离癌组织5cm范围内正常组织)，其中男性63例，女性37例；年龄46~67岁，平均(56.32±3.16)岁；体质量指数(BMI)17~30kg/m2，平均(23.16±2.03)kg/m2；病理类型：鳞癌58例、腺癌42例；病理分级[8]：Ⅰ~Ⅱ级51例、Ⅲ级49例；T分期[9]：T1~T253例、T3~T447例；N分期：N055例、N1~N245例。

德谷门冬双胰岛素注射液治疗2_型糖尿病临床效果及安全性探讨

DOI：10.16658/ki.1672-4062.2023.17.098德谷门冬双胰岛素注射液治疗2型糖尿病临床效果及安全性探讨林生，谢平，陈予福州市长乐区人民医院内分泌科，福建福州350200[摘要]目的研究德谷门冬双胰岛素注射液治疗2型糖尿病的临床效果及安全性。

方法选取于2022年7月—2023年4月福州市长乐区人民医院收治的2型糖尿病患者98例为研究对象，采用随机抓阄法分为两组，每组49例。

两组均联用常规降糖药物治疗，对照组采用甘精胰岛素注射液治疗，观察组采用德谷门冬双胰岛素注射液治疗。

对比两组临床治疗效果、临床症状好转时间和胰岛素用量情况、糖代谢指标、胰岛素功能指标、不良反应发生情况、心血管不良事件发生情况。

结果观察组总有效率高于对照组，差异有统计学意义（P<0.05）。

观察组尿酮体转阴时间、血糖达标时间、胰岛素用量均优于对照组，差异有统计学意义（P< 0.05）。

观察组空腹血糖、餐后2 h血糖、糖化血红蛋白均低于对照组，差异有统计学意义（P<0.05）。

观察组胰岛β细胞功能指数高于对照组，胰岛素抵抗指数、空腹胰岛素低于对照组，差异有统计学意义（P<0.05）。

两组恶心呕吐、倦怠乏力、低血糖总发生率比较，差异无统计学意义（P>0.05）。

两组心绞痛、心力衰竭总发生率比较，差异无统计学意义（P>0.05）。

结论德谷门冬双胰岛素注射液治疗2型糖尿病临床效果显著优于甘精胰岛素注射液，但是治疗安全性无显著变化。

[关键词] 2型糖尿病；德谷门冬双胰岛素注射液；不良反应；心血管不良事件[中图分类号] R59 [文献标识码] A [文章编号] 1672-4062（2023）09（a）-0098-04Discussion on the Clinical Effect and Safety of Insulin Degludec and Insu⁃lin Aspart Injection in the Treatment of Type 2 Diabetes MellitusLIN Sheng, XIE Ping, CHEN YuDepartment of Endocrinology, Changle District People's Hospital, Fuzhou, Fujian Province, 350200 China[Abstract] Objective To study the clinical effect and safety of insulin degludec and insulin aspart injection in the treatment of type 2 diabetes mellitus. Methods A total of 98 patients with type 2 diabetes admitted to Fuzhou Changle District People's Hospital from July 2022 to April 2023 were selected as the study objects and divided into two groups with 49 cases in each group by random lottery method. Both groups were treated with conventional hypoglycemic drugs, the control group was treated with insulin glargine injection, and the observation group was treated with Degu asparton double insulin injection. The clinical therapeutic effect, time of improvement of clinical symptoms, insulin dosage, glucose metabolism index, insulin function index, occurrence of adverse reactions and cardiovascular adverse events were compared between the two groups. Results The total effective rate of the observation group was higher than that of the control group, and the difference was statistically significant (P<0.05). The time of urine ketone body turning negative, blood glucose reaching standard and insulin dosage in observation group were better than those in control group, and the differences were statistically significant (P<0.05). Fasting plasma glucose, 2-hour postprandial blood glucose and glycated hemoglobin in the observation group were lower than those in the control group, and the differences were statistically significant (P<0.05). The function index of islet β cells in observation group was higher than that in control group, the insulin resistance index and fasting insulin was lower than that in control group, the dif⁃ference was statistically significant (P<0.05). There was no statistically significant difference in the total incidence of [作者简介]林生（1981-），男，本科，副主任医师，研究方向为糖尿病及其并发症的相关临床研究。

乙酰胆碱酯酶抑制剂

上海应用技术学院研究生课程《高等天然产物化学》试卷2014 / 2015 学年第1 学期课程代码：NX0702013论文题目：乙酰胆碱酯酶抑制剂的研究进展姓名：芮银146061414康满满146061409专业：制药工程学院：化工学院乙酰胆碱酯酶抑制剂的研究进展芮银，陈祎桐，康满满摘要：本文阐述了乙酰胆碱酯酶抑制剂(AChEI)的研究进展，介绍了用于药物治疗的乙酰胆碱酯酶抑制剂的各种来源如植物、微生物等，及其抑制乙酰胆碱的活性物质。

在此基础上，总结了几种现代分析技术，对AChEIs进行筛选，大大加快AD药物资源的开发利用进程。

这些方法主要有基于比色法的Ellman's法及相关的改进方法、薄层显色法、荧光显色法、电喷雾质谱法等。

但是，到目前为止，现代分析技术在AD药物资源中的应用还处在起步阶段。

关键词：乙酰胆碱酯酶抑制剂，筛选方法，薄层显色法，荧光显色法The progress of acetylcholinesteraseinhibitorsRui Yin, Chen Yitong, Kang ManmanAbstract：In this artical, the research elaborates progress of acetylcholinesterase inhibitors (AChEI), and introduces a variety of sources for drug treatment acetylcholinesterase inhibitors such as plants, microorganisms, and its active ingredients. On this basis, the review summarizes several modern analytic techniques such as Ellman's method which based on the colorimetric method, TLC chromogenic method, fluorescent color method, Electrospray ionization mass spectrometry and so on. However, at present, the application of modern analytic techniques in AD drug resources is still in infancy.Key word: Acetylcholinesterase inhibitors, Screening Methods, TLC chromogenic method, Fluorescent color method目录摘要.................................................................................................错误!未定义书签。

UPLC-MS

UPLC-MS/MS法同时快速测定保健食品中10种降压类非法添加化学药王晓峰，许琨琨，卢文斌，吴芳海，蔡振世*，林晓明（泉州市食品药品检验所，福建泉州 362000）摘要：目的：建立同时测定保健食品中10种降压类非法添加化学药的UPLC-MS/MS快速检测方法。

方法：液相采用ACQUITY UPLC®BEH C18（2.1 mm×100 mm，1.7 μm）柱，以超纯水（含0.1%甲酸）-乙腈（0.1%甲酸）为流动相，进行梯度洗脱，进样量2 μL，流速0.3 mL·min-1，柱温30 ℃。

质谱采用ESI，正、负离子多反应监测模式，进行定性分析和定量分析。

结果：盐酸普萘洛尔、酒石酸美托洛尔、艾司洛尔、比索洛尔、坎地沙坦、厄贝沙坦、替米沙坦、氯沙坦、缬沙坦和吲达帕胺的分离度良好，线性范围内相关性均较好，R2均大于0.996 3；平均回收率为93%～118%；RSD为1.4%～4.9%（n=6）；方法检出限为0.10～5.00 μg·kg-1；方法定量限为0.30～15.00 μg·kg-1；单次分析仅需12 min。

结论：该方法操作便捷、检测时间短、灵敏度高、结果准确，适用于保健食品中10种降压类非法添加化学药的快速筛查及定量检测。

关键词：UPLC-MS/MS；保健食品；降压类药物Simultaneous and Rapid Determination of 10 illegally Added Antihypertensive Chemicals in Health Food by UPLC-MS/MS WANG Xiaofeng, XU Kunkun, LU Wenbin, WU Fanghai, CAI Zhenshi*, LIN Xiaoming(Quanzhou Institute for Food And Drug Control, Quanzhou 362000, China) Abstract: Objective: To establish a UPLC-MS/MS rapid detection method for simultaneously determining 10 illegally added chemical antihypertensive drugs in health foods. Method: ACQUITY UPLC®BEH C18( 2.1 mm×100 mm, 1.7 μm) column was used in the liquid phase with ultrapure water (containing 0.1% formic acid)-acetonitrile (0.1% formic acid) as the mobile phase for gradient elution, the injection volume was 2 μL, ﬂow rate was 0.3 mL·m in-1, and column temperature was 30 ℃. The mass spectrometry was performed by ESI, positive/negative ion multiple reaction monitoring mode for qualitative and quantitative analysis. Result: The separation degree of propranolol, metoprolol, amlodipine, bisoprolol, candesartan, irbesartan, telmisartan, losartan, valsartan, and indapamide was good, and the linear range correlations were good, all R2 values were greater than 0.996 3. The average recovery rate was 93%～118%. RSD was 1.4%～4.9% (n=6). The LOD was between 0.10～5.00 μg·kg-1, and the LOQ was between 0.30～15.00 μg·kg-1. A single analysis only requires 12 min. Conclusion: The method is simple to operate, has short detection time, high sensitivity, and accurate results, and it is suitable for the rapid screening and quantitative detection of 10 illegally added chemical antihypertensive drugs in health foods.Keywords: UPLC-MS/MS; health food; antihypertensive drugs随着近年来我国经济的迅速发展，人们的生活质量得到了很大提高，同时老年人口不断增加，导致出现越来越多的高血压患者，市场上也出现了越来越多的辅助降压类保健食品。

德谷门冬双胰岛素注射液治疗2_型糖尿病的疗效及安全性研究

DOI：10.16658/ki.1672-4062.2023.19.084德谷门冬双胰岛素注射液治疗2型糖尿病的疗效及安全性研究戴卉，张开凤，朱凤丽江苏省镇江市丹徒区人民医院内分泌科，江苏镇江212000[摘要]目的探讨德谷门冬双胰岛素注射液在2型糖尿病中的效果以及安全性。

方法选取2022年1月—2023年7月江苏省镇江市丹徒区人民医院收治的62例2型糖尿病患者为研究对象，按随机数表法分为对照组（n=31）和观察组（n=31）。

对照组患者接受门冬胰岛素30注射液治疗，观察组患者接受德谷门冬双胰岛素注射治疗。

对比两组患者临床疗效、血糖变化和不良反应发生率。

结果观察组治疗有效为96.77%，高于对照组的77.42%，差异有统计学意义（χ2=5.167，P=0.023）。

治疗前，两组患者血糖水平比较，差异无统计学意义（P>0.05）；治疗后，两组患者血糖水平均改善，且观察组血糖指标低于对照组，差异有统计学意义（P< 0.05）。

观察组不良反应发生率低与对照组，差异有统计学意义（P<0.05）。

结论德谷门冬双胰岛素的应用可以明显改善2型糖尿病患者血糖水平，疗效更为确切，且安全性更高，不会增加用药后不良反应。

[关键词] 2型糖尿病；德谷门冬双胰岛素；门冬胰岛素30注射液；安全性[中图分类号] R587 [文献标识码] A [文章编号] 1672-4062（2023）10（a）-0084-04Study on the Efficacy and Safety of Insulin Degludec and Insulin Aspart Injection in the Treatment of Type 2 Diabetes MellitusDAI Hui, ZHANG Kaifeng, ZHU FengliDepartment of Endocrinology, Zhenjiang Dantu District People's Hospital, Zhenjiang, Jiangsu Province, 212000 China [Abstract] Objective To explore the effect and safety of insulin degludec and insulin aspart injection in type 2 diabe⁃tes mellitus.Methods 62 patients of type 2 diabetes mellitus patients admitted to Zhenjiang Dantu District People's Hospital, Jiangsu Province from January 2022 to July 2023 were selected as study objects and divided into the control group (n=31) and the observation group (n=31) by taking the random number table method. The patients in the control group were treated with insulin aspart 30 injection and the patients in the observation group were treated with insulin degludec and insulin aspart injection. Compared the clinical efficacy, the changes in blood glucose and the incidence of adverse reactions between the two groups of patients.Results The treatment effectiveness of the observation group was 96.77%, which was higher than that of the control group, which was 77.42%, and the difference was statistically significant (χ2=5.167, P=0.023). There was no statistically significant difference in blood glucose levels between the two groups before treatment (P>0.05). After treatment, blood glucose levels improved in both groups, and the level of blood glucose in the observation group were lower than those in the control group, and the difference was statistically significant (P<0.05). The incidence of adverse reactions in the observation group was lower than that in the control group, and the difference was statistically significant (P<0.05).Conclusion The application of insulin degludec and in⁃sulin aspart can significantly improve the blood glucose level of patients with type 2 diabetes mellitus, the efficacy is more accurate, and the safety is higher, and it will not increase the occurrence of adverse reactions after the use of medication.[作者简介]戴卉（1985-），女，本科，主治医师，研究方向为内分泌科。

达格列净联合二甲双胍治疗对2_型糖尿病患者血糖、胰岛敏感性的影响

DOI：10.16658/ki.1672-4062.2024.01.061达格列净联合二甲双胍治疗对2型糖尿病患者血糖、胰岛敏感性的影响郑婷婷1，陈李燊2，饶志辉1，林美玲11.福建医科大学附属龙岩第一医院药剂科，福建龙岩364000；2.厦门大学附属福州第二医院药剂科，福建福州350007[摘要]目的探讨达格列净联合二甲双胍治疗对2型糖尿病（Type 2 Diabetes Mellitus， T2MD）患者血糖、胰岛敏感性的影响。

方法选取2020年7月—2022年6月福建医科大学附属龙岩第一医院收治的70例T2MD患者，按随机数表法分为联用组（n=35）与单用组（n=35）。

单用组给予二甲双胍，联用组给予达格列净联合二甲双胍，比较两组疗效。

结果治疗后，联用组空腹血糖、糖化血红蛋白餐后2 h血糖、胰岛素抵抗指数、丙二醛、终末氧化蛋白产物水平低于单用组，胰岛素分泌指数、胰岛素敏感性指数、总抗氧化能力、超氧化物歧化酶、过氧化氢酶水平高于单用组，差异有统计学意义（P均<0.05）。

结论达格列净联合二甲双胍治疗可有效调节T2MD患者糖代谢，增强胰岛敏感性，减轻胰岛素抵抗状况，控制血糖水平，明显改善机体氧化-抗氧化平衡。

[关键词] 2型糖尿病；达格列净；二甲双胍；血糖；胰岛敏感性[中图分类号] R9 [文献标识码] A [文章编号] 1672-4062（2024）01（a）-0061-04Effect of Dapagliflozin Combined with Metformin Treatment on Blood Glucose and Islet Sensitivity in Type 2 Diabetes Mellitus PatientsZHENG Tingting1, CHEN Lishen2, RAO Zhihui1, LIN Meiling11.Department of Pharmacy, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, Fujian Province, 364000 China;2.Department of Pharmacy, Fuzhou Second Hospital Affiliated to Xiamen University, Fuzhou, Fujian Province, 350007 China[Abstract] Objective To investigate the effects of dapagliflozin combined with metformin treatment on blood glucose and islet sensitivity in patients with type 2 diabetes mellitus (T2MD). Methods 70 T2MD patients admitted to Long⁃yan First Hospital Affiliated to Fujian Medical University from July 2020 to June 2022 were selected and divided into the combination group (n=35) and the monotherapy group (n=35) by random number table method. Metformin was given to the monotherapy group and dapagliflozin combined with metformin was given to the combination group to com⁃pare the efficacy of the two groups. Results After treatment, the levels of glucose, glycasylated hemoglobin, 2-hour plasma glucose, homeostatic model assessment-insulin resistance, malondialdehyde, and advanced oxidation protein product were lower in the combination group than those in the monotherapy group, and the levels of homeostasis model assessment-insulin sensitivity, homeostasis model assessment-β, total-antoxidant capability, superoxide dis⁃mutase, and catalase were higher than those in the monotherapy group, and the differences were statistically signifi⁃cant (all P<0.05).Conclusion Dapagliflozin combined with metformin treatment can effectively regulate glucose me⁃tabolism in T2MD patients, enhance islet sensitivity, reduce insulin resistance status, control blood glucose levels, and significantly improve the oxidation-antioxidant balance of the body.[作者简介]郑婷婷（1983-），女，本科，主管药师，研究方向为医院药学。

SKI-II-LCMS-20601-MedChemExpress

=====================================================================Acq. Operator : Su Xiao Ying(LCMS-02) Seq. Line : 46Acq. Instrument : HY-LCMS-02 Location : P1-F-04Injection Date : 6/2/2016 1:42:02 PM Inj : 1Inj Volume : 3.000 µlAcq. Method : D:\AGLIENT 1260\DATA\20160602\20160602 2016-06-02 08-59-29\100-1000MS+3MIN- 1.5_(0.02%FA).MLast changed : 6/2/2016 8:59:29 AM by Su Xiao Ying(LCMS-02)Analysis Method : D:\AGLIENT 1260\DATA\20160602\20160602 2016-06-02 08-59-29\100-1000MS+3MIN- 1.5_(0.02%FA).M (Sequence Method)Last changed : 6/3/2016 10:10:48 AM by Su Xiao Ying(LCMS-02) (modified after loading)M ethod Info : HY-365_5HO1RS,M,A-RP-108，210nm,23minCatalog No : HY-13822 Batch#20601 A-RP-153Additional Info : Peak(s) manually integratedmin*0.511.522.53mAU 020040060080010001200*DAD1 B, Sig=214,4 Ref=off (D:\AGLIENT 1260\DATA\20160602\20160602 2016-06-02 08-59-29\BIZ2016-602-WJ2.D)2.2222.4112.526===================================================================== Area Percent Report =====================================================================Sorted By : Signal Multiplier : 1.0000Dilution : 1.0000Do not use Multiplier & Dilution Factor with ISTDsSignal 1: DAD1 B, Sig=214,4 Ref=offSignal has been modified after loading from rawdata file!Peak RetTime Type Width Area Height Area # [min] [min] [mAU*s] [mAU] %----|-------|----|-------|----------|----------|--------| 1 2.222 MM 0.0425 3502.45972 1374.85510 98.6938 2 2.411 MM 0.0778 29.06973 6.23061 0.8191 3 2.526 MM 0.0558 17.28664 5.16699 0.4871Totals : 3548.81609 1386.25269===================================================================== *** End of Report ***=====================================================================Acq. Operator : Su Xiao Ying(LCMS-02) Seq. Line : 46Acq. Instrument : HY-LCMS-02 Location : P1-F-04Injection Date : 6/2/2016 1:42:02 PM Inj : 1Inj Volume : 3.000 µlAcq. Method : D:\AGLIENT 1260\DATA\20160602\20160602 2016-06-02 08-59-29\100-1000MS+3MIN- 1.5_(0.02%FA).MLast changed : 6/2/2016 8:59:29 AM by Su Xiao Ying(LCMS-02)Analysis Method : D:\AGLIENT 1260\DATA\20160602\20160602 2016-06-02 08-59-29\100-1000MS+3MIN- 1.5_(0.02%FA).M (Sequence Method)Last changed : 6/2/2016 2:36:16 PM by Su Xiao Ying(LCMS-02) (modified after loading)M ethod Info : HY-365_5HO1RS,M,A-RP-108，210nm,23minCatalog No : HY-13822 Batch#20601 A-RP-153Additional Info : Peak(s) manually integratedmin0.511.522.5350000100000150000200000250000300000 MSD1 TIC, MS File (D:\AGLIENT 1260\DATA\20160602\20160602 2016-06-02 08-59-29\BIZ2016-602-WJ2.D) ES-API, Pos, Scan2.218MS Signal: MSD1 TIC, MS File, ES-API, Pos, Scan, Frag: 50 Spectra averaged over upper half of peaks. Noise Cutoff: 1000 counts.Reportable Ion Abundance: > 10%.Retention Mol. Weight Time (MS) MS Area or Ion2.218 1761020 305.00 I 304.10 I 303.10 Im/z10020030040050060070020406080100*MSD1 SPC, time=2.198:2.271 of D:\AGLIENT 1260\DATA\20160602\20160602 2016-06-02 08-59-29\BIZ2016-602-WJ2.D ES-API, Max: 157077306.0305.0 303.1*** End of Report ***。

栀子多糖的抗肿瘤活性研究

栀子多糖的抗肿瘤活性研究①SHI R F石若夫1,2,李大力2,田春宇1,王关林3,方宏筠3(1.大连理工大学化工学院,辽宁大连116012;2.南京理工大学化工学院,江苏南京210094;3.辽宁师范大学生命科学学院,辽宁大连116029)摘　要:　采用3种不同的方法分别测定了栀子(Gardenia jasminoides E ills )多糖对3种不同肿瘤细胞的抑制情况,结果表明,栀子多糖具有比较广谱的抑瘤效应。

土豆碟法测定栀子多糖对根癌农杆菌(Agrobacterium tume 2faciens )C58诱导植物根瘤的最高抑制率为68.4%(1.258mg/m L 栀子多糖);MTT 法测定栀子多糖对人红白血病细胞K 562的无毒剂量约为0.4μg/m L ,低毒剂量约为14.33μg/m L ,半致死剂量约为62.61μg/m L ,100μg/m L 栀子多糖对人红白血病K 562细胞的抑制率为63.2%;实体瘤称重法测定栀子多糖对小鼠腹水肝癌Hca 2f 实体瘤的抑制情况表明,栀子多糖口服给药效果优于注射给药的效果,500μg/(kg ・d )的栀子多糖口服对小鼠肝癌实体瘤的抑制率达49%。

关键词:　栀子;多糖;抗肿瘤活性中图分类号:Q949.781.1;R7323 文献标识码:A 文章编号:025322417(2002)0420067204研究表明,许多种植物多糖都具有抗肿瘤活性,特别是一些中药的水溶性多糖。

医学界普遍认为,多糖作为抗肿瘤药物与其提高免疫系统功能有关。

从结构上分析,杂多糖比同多糖抗癌活性更强。

栀子(Gardenia jasminoides E ills )多糖是由鼠李糖、岩藻糖、甘露糖等5种单糖按一定比例组成的易溶于水的大分子。

孟延发等[1]通过活细胞计数法测定了栀子多糖对腹水肝癌细胞和S 2180肉瘤细胞具有较好的抑制作用,其抑制率分别达到58%和51%。

为了考察栀子多糖抑制肿瘤细胞的广谱性,作者选择了3种抗肿瘤测定方法分别就栀子多糖对植物根癌农杆菌引起的根瘤、人红白血病K 562细胞和小鼠腹水肝癌Hca 2f 实体瘤的抑制情况进行了研究。

原位电化学辅助还原制备石墨烯_金纳米粒子@多酸杂化薄膜及DPV法检测血液中的尿酸鲍雅妍

原位电化学辅助还原制备石墨烯/金纳米粒子@多酸杂化薄膜及DPV法检测血液中的尿酸鲍雅妍发布时间：2021-07-28T07:44:26.569Z 来源：《中国科技人才》2021年第12期作者：鲍雅妍1 鲍善霞2 张健3 冯锋4 [导读] 本文采用电化学辅助还原法成功制备了还原态氧化石墨烯/金纳米粒子@多酸纳米杂化薄膜。

制备过程可在1小时内完成。

所制备的{PEI/rGO/Au@P2W18}电极仅负载单层催化剂，DPV法检测尿酸具有良好的线性关系，较低的检出限，优良的灵敏度。

可用于血样中尿酸的测定。

鲍雅妍1 鲍善霞2 张健3 冯锋4山西大同大学化学环境与工程学院 037009摘要：本文采用电化学辅助还原法成功制备了还原态氧化石墨烯/金纳米粒子@多酸纳米杂化薄膜。

制备过程可在1小时内完成。

所制备的{PEI/rGO/Au@P2W18}电极仅负载单层催化剂，DPV法检测尿酸具有良好的线性关系，较低的检出限，优良的灵敏度。

可用于血样中尿酸的测定。

关键词：多酸；石墨烯；金纳米粒子；复合薄膜；尿酸石墨烯作为近年来关注度最高的新兴材料，由于其高比表面积[1]、优良的力学性能[2]，以及负载电荷高速移动[3]性能等的优点，在储能[4]、催化[5]、电池[6]、超级电容器[7]、化学传感器[8]和生物传感器[9]等领域引起了科学家们的广泛的关注。

而其前驱体氧化石墨烯（GO），易于与其他材料结合，是更为普遍的碳基纳米材料[10]。

通过紫外光照或电化学还原的方法可将GO与纳米级的多酸结合[11]，可同时实现GO的还原和多酸的负载，并形成石墨烯/多酸二元复合物。

并且由于它们之间的协同效应，使得这两种材料的优点得以更好的发挥。

基于上述考虑，本文开发了一种通过电化学辅助还原原位制备的{PEI/rGO/Au@P2W18}纳米杂化膜。

通过对UA检测结果表明，修饰电极具有检出限低、线性范围宽、灵敏度高、选择性好等特点。

1 实验部分1.1 试剂与仪器K6[P2W18O62]·19H2O（P2W18）根据文献方法合成[12]。