基于网络药理学与分子对接探讨异鼠李素对缺血性神经损伤的治疗作用.采用ChEMBL、SwissTargetPrediction、Drug?Bank、STITCH及BindingDB数据库检索异鼠李素药理学靶点,应用DisGeNET、GenCLiP及CTD数据库检索缺血性神经损伤的疾病靶点,取交集作为异鼠李素对缺血性神经损伤的治疗靶点,并进行表型分析.将交集靶点导入STRING构建蛋白互作网络,使用Network analyser进行拓扑分析,同时应用MODE构建功能模块,并基于ClueGo对功能模块进行分析.之后应用DA?VID数据库对治疗靶点进行GO及KEGG富集分析.利用Discovery Studio评价异鼠李素与核心靶点的结合活性,最后建立OGD/R损伤PC12细胞模型,采用MTT和LDH法检测细胞活力,Western blot法对AKT1、IL6和MMP2的表达进行检测.异鼠李素通过50个缺血性神经损伤相关靶点,调控细胞凋亡、转录、蛋白质磷酸化、炎症反应等生物学过程,干预PI3K?AKT信号通路、HIF?1信号通路、雌激素信号通路、肿瘤坏死因子信号通路、FoxO信号通路等多条途径发挥抗缺血性神经损伤的作用.初步阐释异鼠李素治疗缺血性神经损伤的作用,涉及多靶点、多通路,为进一步探究其药理学活性奠定理论基础.

设计合成了一类可聚合固化且具有良好生物降解性能的组织黏附材料.材料使用前为单体分子,常温下呈液态,单体结构含有寡聚乳酸(OLA)片段和氰基丙烯酸酯(CA)官能团.在接触到肌体组织时,单体可通过CA官能团发生分子间聚合形成梳状聚合物并产生黏附.聚合物中的OLA侧链结构可赋予其良好的生物相容性和可降解性.合成了OLA末端分别为羧基或苄基的两种单体(OLA4-CA和OLA4 B-CA),通过核磁氢谱鉴定了单体化学结构,采用剪切拉伸强度和固化时间表征组织黏附能力,利用凝胶渗透色谱测试聚合物分子量,在体内、外模型中评价聚合物的降解性能,通过植入试验研究聚合物的生物相容性,此外,采用体外抑菌圈试验测试了材料的抑菌性能.试验结果表明:成功合成了目标单体;单体接触肌体组织可在3 min内聚合固化并产生有效的黏附能力;聚合物的降解性能与侧链OLA片段的末端羧基结构相关;优选的OLA4-CA的聚合物在小鼠体内植入模型中12 h左右即被完全降解吸收,且具有良好的生物相容性;此外,在体外抑菌试验中,材料显示出浓度依赖性的抑菌能力.这类可聚合固化材料有望进一步用于新型创伤敷料和组织粘附材料的开发.

目的:通过观察连续4周给予复方利血平氨苯蝶啶片对自发性高血压大鼠(spontaneously hypertensive rat,SHR)的血压以及肠道菌群的影响,探讨其作用与肠道菌群调控之间的关系.方法:将40只SHR大鼠随机分为模型组(SHR)、培哚普利组(P)、复方利血平氨苯蝶啶片低剂量组(JL)和高剂量组(JH),另设10只Wistar大鼠为正常对照组(WKY).各组均采取灌胃给药连续4周.每周测定并记录血压,末次给药后检测尿液钠离子、钾离子和血清醛固酮(aldosterone,Ald)含量;采集粪便提取大鼠肠道微生物总RNA,通过16SrRNA高通量测序对肠道菌群进行测序分析.结果:与SHR组相比,给药4周后JH组大鼠的收缩压和舒张压显著降低(P<0.05).与SHR组相比,JL组和JH组大鼠血清醛固酮含量降低、尿液钠离子含量显著升高(P<0.05).JL组、JH组及P组干预后菌群丰度与多样性增加.关联性分析显示,SHR大鼠血清醛固酮含量与乳酸细菌科(Lactobacillaceae)、厚壁菌科(unclassified p Firmicutes)等丰度显著相关,尿液中钠离子含量与氨基酸球菌科(Acidaminococcaceae)、萨特菌科(Sutterellaceae)等丰度显著相关.结论:复方利血平氨苯蝶啶片可改善SHR大鼠菌群丰度与多样性,促进毛螺旋科菌属、普雷沃科菌属、Muribaculaceae、Blautia等有益菌生长,抑制梭状芽孢杆菌属等有害菌增殖,对其发挥抗高血压作用具有重要意义.

目的:采用网络药理学分析和实验验证相结合的方法,研究芪蛭通络胶囊对脑缺血再灌注损伤的治疗作用和作用机制.方法:利用网络药理学的方法获取芪蛭通络胶囊中的化学成分和潜在靶点并获得脑缺血再灌注病理过程相关的靶点,构建"中药-化合物-疾病网络图",同时对核心靶点进行京都基因与基因组百科全书数据库(Kyoto Encyclopedia of Genes Genomes,KEGG)富集分析;采用线栓法制作大鼠右侧大脑中动脉缺血90 min再灌注模型,观察芪蛭通络胶囊0.8、1.6、3.2 g/kg和阳性药尼莫地平30 mg/kg给药7 d后的治疗作用;采用神经行为学评分和矿场试验检测大鼠神经功能和运动能力;TTC染色、苏木素伊红(hematoxy-lin-eosin,HE)染色、尼氏染色检测以及酶联免疫吸附法检测脑组织损伤和相关指标的变化;Western Blot检测Toll样受体4/髓样分化因子/核因子 κB(toll-like receptor 4/myeloiddifferentiationfactor88/nuclear factor kappa-B,TLR4/MyD88/NF-KB)通路和 NOD 样受体蛋白3(nod-like receptor protein 3,NLRP3)炎症小体相关蛋白的变化.结果:网络药理学分析揭示,芪蛭通络胶囊治疗脑缺血再灌注的主要活性成分包括常春藤素、异欧前胡素、芒柄花黄素等19种化合物,其中涉及磷酯酰肌醇-3激酶/蛋白激酶B(phosphatidylinos-itol-3-kinase/protein serine threonine kinase,PI3K/AKT)信号通路、炎症信号通路、Toll样受体信号通路、NOD样受体信号通路等.实验研究表明,与模型对照组相比,芪蛭通络胶囊各组和尼莫地平30 mg/kg组均能明显改善脑缺血再灌注后大鼠神经功能和运动能力,减小缺血部位脑梗死体积(P＜0.05或P＜0.01),有效改善病理损伤,明显调控MyD88、NFκB、NLRP3、半胱氨酸天冬氨酸蛋白酶-1(cysteinyl aspartate specific proteinase-1,Caspase1)蛋白表达(P＜0.05或P＜0.01).结论:网络药理学及实验验证表明芪蛭通络胶囊可能通过TLR4/MyD88/NFKB通路及NLRP3炎症小体治疗脑缺血再灌注损伤.

复方利血平氨苯蝶啶片是由我国学者研发的复方降压药,至今仍在临床广泛使用,但其降压作用机制仍有待阐释.本文拟基于网络药理学分析其降压作用机制并在细胞水平进行初步研究验证.本文通过Swiss Target Prediction数据库收集复方利血平氨苯蝶啶片中4种化学成分的作用靶点;通过TTD、OMIM数据库选取高血压病的相关蛋白靶标;利用STRING数据库构建复方利血平氨苯蝶啶片-高血压病网络模型;通过Metascape数据库对交集靶点进行GO富集分析和通路富集分析;采用人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVEC)和血管平滑肌细胞(vascular smooth muscle cells,VSMC)分别经1μmol·L-1血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)诱导处理,低中高浓度复方利血平氨苯蝶啶片原料(0.01、0.1和1μmol·L-1)进行干预,Western blot法检测HUVEC中磷酯酰肌醇-3激酶/蛋白激酶B/内皮型一氧化氮合酶(phosphatidylinositol-3-kinase/protein serine threonine kinase/endothelial nitric oxide synthase,PI3K/Akt/eNOS)通路和VSMC中环磷酸鸟苷酸/环磷酸鸟苷酸依赖的蛋白激酶G(cyclic guanosinc monophosphate/cGMP-dependent protein kinase,cGMP/PKG)通路的变化.网络药理学分析揭示,复方利血平氨苯蝶啶片降压作用与血管张力调节、肾上腺素受体激活、蛋白激酶活性等密切相关,其中涉及cGMP/PKG信号通路、血管平滑肌收缩、调控神经活动的配体-受体相互作用、心肌细胞肾上腺素信号传导、钙信号通路等信号通路.细胞水平研究证实,复方利血平氨苯蝶啶片处理升高HUVEC中磷酸化磷酯酰肌醇-3激酶(phosphorylated phosphatidylinositol-3-kinase,p-PI3K)、磷酸化蛋白激酶B(phosphorylated protein serine threonine kinase,p-Akt)、磷酸化内皮型一氧化氮合酶(phosphorylated endothelial nitric oxide synthase,p-eNOS)以及VSMC中eNOS、磷酸化血管舒张剂刺激磷蛋白(phosphorylated vasodilator-stimulated phosphoprotein,p-VASP)、PKG蛋白水平.复方利血平氨苯蝶啶片通过多靶点、多通路发挥降压作用,进一步研究证实,激活PI3K/Akt/eNOS通路诱导内皮依赖的NO/cGMP/PKG信号,从而舒张血管可能是其重要作用机制之一.

目的 复方利血平氨苯蝶啶片是用于临床治疗高血压病的复方降压药,由我国学者研发,在临床应用多年,但其降压作用机制仍有待阐释.本文通过网络药理学分析其降压作用机制并在细胞水平进行初步研究验证.方法 本文利用Swiss Target Prediction数据库获得复方利血平氨苯蝶啶片中利血平、氨苯蝶啶、氢氯噻嗪和硫酸双肼屈嗪4种化学成分的作用靶点;通过TTD、OMIM数据库查找并获取高血压病的相关蛋白靶标;利用蛋白互作网络分析数据库构建复方利血平氨苯蝶啶片-高血压病网络模型;通过Metascape数据库对潜在靶点进行GO富集分析和通路富集分析;采用人脐静脉内皮细胞和血管平滑肌细胞分别经血管紧张素Ⅱ1μmol·L-1诱导处理,低中高浓度复方利血平氨苯蝶啶片原料(0.01,0.1和1μmol·L-1)进行干预,Western印迹法检测人脐静脉内皮细胞中PI3K/Akt/eNOS通路和血管平滑肌细胞中cGMP/PKG通路的变化.结果 网络药理学结果表明,复方利血平氨苯蝶啶片可能通过参与管径调节、血管张力调节、全身动脉血压的负向调节、肾上腺素受体激活、蛋白激酶活性等实现降压,降压过程中可能涉及cGMP/PKG信号通路、血管平滑肌收缩、调控神经活动的配体-受体相互作用、心肌细胞肾上腺素信号传导、钙信号通路等信号通路.细胞水平的研究结果证明,复方利血平氨苯蝶啶片处理后,可以升高人脐静脉内皮细胞中p-PI3K、p-Akt、p-eNOS以及血管平滑肌细胞中eNOS、p-VASP、PKG蛋白水平.结论 复方利血平氨苯蝶啶片有效地控制血压,预防和减少心血管事件是通过多靶点、多通路发挥降压作用,进一步研究证实,激活PI3K/Akt/eNOS通路诱导内皮依赖的NO/cGMP/PKG信号,从而舒张血管可能是其重要作用机制之一.

目的 探讨丹酚酸A(SalA)对慢性脑缺血(CCI)大鼠认知损伤及神经炎症的影响.方法 采用双侧颈总动脉结扎(2VO)法建立大鼠CCI模型,术后28 d采用Morris水迷宫(MWM)筛选模型,将造模成功大鼠随机分为2VO组,2VO+SalA(5,10和20 mg·kg-1)组,2VO+尼莫地平组,另设假手术组作为对照.通过MWM和旷场试验观察各组大鼠的认知功能,包括学习记忆能力和探索能力;采用HE染色、Nissl染色观察大鼠皮质和海马区的病理变化;通过酶联免疫吸附实验(ELISA)和免疫组化分析检测皮质和海马区炎症因子的表达和胶质细胞的活化.结果 MWM测试显示,在空间探索实验中,SalA(5,10和20 mg·kg-1)明显缩短CCI大鼠潜伏期(P<0.05),尼莫地平有缩短潜伏期的趋势但是效果不明显,SaLA 10和20 mg·kg-1组和尼莫地平组在60 s内穿越平台所在位置的次数明显增加(P<0.05).旷场测试显示,与模型组相比,2VO+NS组的运动总距离(P<0.01)、站立次数(P<0.01)和进入中心区域的频率(P<0.05)显著降低.HE染色显示,正常神经元数目减少,可见神经细胞脱失,细胞形态不规则排列紊乱,出现神经细胞变性坏死,SalA可以改善这一现象,效果优于尼莫地平.Nissl染色显示,SalA 20 mg·kg-1和尼莫地平治疗可以显著减少CCI大鼠皮质神经元缺失(P<0.05),并且SalA 10和20 mg·kg-1可以显著减少CCI大鼠海马神经元缺失(P<0.05),而尼莫地平无显著作用.ELISA检测表明,SalA治疗明显降低了CCI大鼠皮质和海马区炎症因子TNF-α,IL-1β和IL-6的表达水平,而尼莫地平只对皮质区IL-6的表达具有明显降低的作用(P<0.05).免疫组化结果显示,经SalA治疗,CCI大鼠海马和皮质区GFAP、CD68的表达被明显降低(P<0.05),而尼莫地平对2种蛋白的表达都没有影响.结论 SalA可以通过降低炎症反应,减轻CCI引起的大鼠认知功能损伤.

目的 研制一种具有抗菌性能的医用粘合剂,表征其物理化学性能,评价其对大鼠感染性创伤的治疗效果,并阐明抗菌剂体内外释放及分布规律.方法 按2％载药率称取适量三氯生(triclosan,TCS)溶于PEG2000交联的氰基丙烯酸酯生物可降解粘合剂(biodegradable adhesive,BDA)中,获得具有抗菌性能的医用胶TCS-BDA.使用高效液相色谱、紫外分光光度法和拉力实验进行TCS-BDA的理化性能分析;体外评价TCS-BDA的透皮释放性能;滤纸片法评价TCS-BDA体外抗菌活性;测试TCS在大鼠的体内分布及局部浓度;用大鼠感染性创伤模型评价TCS-BDA的长效抗菌作用及对伤口愈合的治疗效果.结果 TCS能物理均匀分散于液态BDA中,且TCS-BDA具备良好的粘接性能.TCS可以从BDA聚合物基质中释放并进入皮肤组织,少量进入血液,第144 h后动物体内无法检测到TCS.与此同时,TCS-BDA在体内外模型中均显示了良好的促伤口粘合和长效抗菌作用.结论 成功制备了一种新型TCS-BDA抗菌医用胶,在大鼠感染性创伤模型中,TCS-BDA可使伤口快速闭合,同时有效控制金黄色葡萄球菌感染.TCS-BDA使用的医用胶BDA较传统氰基丙烯酸正丁酯医用胶更有助于抗菌药物TCS的释放和透皮,也达到了良好的缓释效果.

Objective To explore the function of flaxseed powder lingans on the prevention of breast cancer and the relation with estrogen on the ovariectomized female rats.Methods Fouty-eight female wistar rat were randomly divided into basal diet group(BD),basal diet castrate group(BDC),flaxseed group(FS) and flaxseed castrate group(FSC),All of the rats were treated with DMBA by intragastric administration at a dose of 2mg/kg weight to establish the experimental animal models of induced breast cancer and the BDC and FSC groups were operated for the ovariectomy.On the 21 week the volume and weight of the palpable tumors were measured and conducted pathological examination by pathologist.Results The experimental animals were generally in well situation,there was no obvious toxic or side effect in experimental groups,palpable tumors appeared two to four weeks later in FS and FSC groups than that in the control;Compared with the control groups,the incidence and the average number of lesions of breast hyperplasia,atypical hyperplasia,breast cancer were significantly lower in flaxseed groups(hyperplasis:FS vs BD,P=0.006**;FSC vs BDC,P<0.001**;atypical hyperplasia:FS vs BD,p=0.048*;FSC vs BDC,P <0.014*;breast cancer:FS vs BD,P=0.028*;FSC vs BDC,P=0.047*),additionally,the volume and weight of the tumors were lower in flaxseed groups.The results also suggested that the ability of inhibiting the hyperplasia and tumor cell growth of the flaxseed lignans is related with estrogen states(hyperplasis:P=0.008**;atypical hyperplasia: P=0.042*;Breast cancer:P=0.033*).Conclusions Flaxseed powder lignans can effectively prevent and reduce the occurrence of breast cancer,precancerous lesions and hyperplasia induced by DMBA,and the preventive effect of flaxseed powder lignans are affected by body estrogen.The above results may be of reference value for screening effective population and preventing breast cancer by lignans.

晚期癌症患者经常伴发呼吸困难症状,严重影响患者的生理、心理功能及生活质量。本文总结了近年来癌症患者呼吸困难的相关研究,介绍了呼吸困难症状的病因及治疗。希望藉此增强患者的治疗信心,改善患者对治疗的依从性和患者的生活质量。

Objective To analyze the serum level of macrophage inhibitory Cytokine-1(MIC-1)in pancreatic cancer patients and its clinical value.Methods Serum levels of MIC-1,CA199 and TBIL in 150 patients with pancreatic cancer or benign diseases and in 120 normal controls were detected by ELISA,ECL and automatic biochemical analyzer,respectively.Results The MIC-1 level in pancreatic cancer group was significantly higher than those in benign disease group and control group(both P<0.001).Through ROC curve,by setting cut-off value as 946 pg/mL,the sensitivity and specificity of MIC-1 achieved 80.5% and 90.1%,respectively,which were superior to CA199(74.6% and 82.2%,respectively).Combined detection of MIC-1 and CA199 increased the sensitivity and specificity to 85.6% and 92.1%.MIC-1 level significantly decreased among responders.Pancreatic cancer patients with jaundice had significantly higher MIC-1 level than those without jundice(P=0.011),and metastatic patients had significantly lower MIC-1 level than those without metastasis(P=0.018).Conclusion MIC-1 is a relatively good marker for the diagnosis and prediction of clinical outcomes of pancreatic cancer.

目的 评价三磷酸腺苷-肿瘤体外药敏检测(adenosine triphosphate-tumor chemosensitivity assay,ATP-TCA)在晚期卵巢上皮癌化疗中的应用价值,以及对该技术应用的成本-效果进行评价.方法 回顾性分析158例在我院例行ATP-TCA检测的晚期卵巢上皮癌病例,其中原发67例,复发91例,为ATP-TCA检测治疗组.根据分期和年龄选取同期153例常规治疗的晚期卵巢上皮癌病例作为对照组;采用半年化疗的临床近期有效率对患者疗效进行评价,并对术后半年内的治疗方案进行统计和费用计算;采用"成本-效果分析(CEA)"法评价ATP-TCA检测技术应用的卫生经济学价值.结果 ATP-TCA检测治疗组与对照组临床近期有效率分别为58.2%和46.4%,两组差异显著(P=0.041);原发病例中,ATP-TCA检测治疗组与对照组临床近期有效率分别为77.6%和71.4%,两组差异无统计学意义(P=0.429);复发病例中,ATP-TCA检测治疗组与对照组临床近期有效率分别为44.0%和28.9%,两组差异显著(P=0.045);ATP-TCA检测治疗组平均费用50293.42元人民币,对照组治疗平均化疗药物费用46495.10元人民币,两组间无显著差异(P=0.210).成本-效果分析结果表明ATP-TCA检测治疗组相对于对照组的边际成本△C/△E为321.89,远小于对照组C/E值1002.00.结论 ATP-TCA检测技术应用在晚期复发性卵巢上皮癌治疗中提高了临床近期疗效;该技术应用的成本-效果明显.

Objective To develop macrophage inhibitory cytokine-1(MIC-1)monoclonal antibody and the test method for serum MIC-1.Methods BALB/C female mice was immuned by MIC-1 antigen.Then hybridoma cell lines secreting monoclonal antibodies against MIC-1 were obtained by hybridoma technology.ELISA serum test method was constructed and performance was evaluated.Results Totally 32 monoclonal antibodies against MIC-1 were successfully obtained.Two hihg-affinity antiboclies were chosen to establish MIC-1 serum rapid detection method.Performance appraisal results showed good linearity,and R2 is greater than 0.999.Intra-and inter-assay coefficient of variation were 5.15% and 9.51% respectively.The average recovery was 98.9%.The MIC-1detection method was stable at 37℃ for up to 3 days and 4℃ for 6 months.Conclusion The indicators of the MIC-1 detection method conform to the related state standards or industrial standards.The MIC-1 ELISA serum test method meets the need of scientific research and clinical test and has entered the industrialization program.

Objective To investigate the clinical value of macrophage inhibitory cytokine-1(MIC-1)in diagnosis,early diagnosis,treatment monitoring and recurrence warning of gastric cancer.Methods Serum samples form179 patients with stages of gastric cancer,9 patients with gastric benign diseases and 200 healthy persons(as were detected by MIC-1 assay kit for MIC-1 level.And some of tumor patients were followed up.CEA and CA19-9 were tested by Roche Cobas 601 ECL analyzer.Results MIC-1 level in gastric cancer patients was significantly higher than that in benign disease patients and normal persons(951.68±785.40,532.92±222.16,391.56±299.55,P<0.001).MIC-1 have more sensitivity than CEA and CA19-9 in patients with early gastric cancer(stage Ⅰ:28.6%,8.6% and 5.7%;stage Ⅱ:37.8%,17.8% and 0%).Combined detection of CEA,CA19-9 and MIC-1 increased the sensitivity from 18.4% of CEA,10.1% of CA19-9 to 52.0%,which was significantly better than the detection of MIC-1,CEA and CA19-9 alone.MIC-1 level decreased significantly after effective treatment(P=0.004),and significantly increased at recurrence(P =0.002).Conclusion MIC-1 is a new and effective gastric cancer biomarker in serum for the diagnosis of gastric cancer.It has important clinical value in improving early diagnosis and monitoring clinical response.

Objective To analyze the serum concentration and its application value of macrophages inhibitory cytokine-1(MIC-1)in patients with esophageal cancer.Methods Double antibody sandwich ELISA method was used to detect the serum MIC-1 level of 141 patients with esophageal cancer,3 patients with benign esophageal diseases and 200 healthy persons(as normal control).ECL was used to detect the serum CA19-9 and CEA concentration of these samples.Results MIC-1 concentration in esophageal cancer patients was significantly higher than that in normal control(P<0.001)and benign disease group.According to ROC curve.when 550 pg/ml was set as the cut-off value for the diagnosis of esophageal cancer,the specificity and sensitivity of MIC-1 achieved 76.7% and 82.3%,which were superior to CEA and CA19-9.MIC-1 concentration increased with TNM staging,but the patients with metastatic carcinoma(stage IV)had a lower serum MIC-1 level.Conclusion MIC-1 may become a novel serum marker of esophageal cancer and it has certain application value in the diagnosis of esophageal cancer,especially in the early stage of esophageal cancer.

Objective To study the clinical value of serum macrophages inhibitory cytokine-1(MIC-1)level in patients with lung cancers.Methods The double antibody sandwich ELISA was used to detect serum MIC-1 level in 79 lung cancer patients(lung cancer group),8 benign pulmonary disease patients(benign disease group)and 200 bealthy persons(normal control group).ELC were used to detect the serum CA125,CEA,NSE,SCC and Cyfer21 level.Results MIC-1 concentration in lung cancer group was significantly higher than that in normal control group(P<0.001)and benign disease group(P=0.005).According to ROC curve and MIC-1 level of normal control group,when 1000pg/ml of MIC-1 as the cut-off value,the specificity and sensitivity were 97% and 64.6%,respectively.MIC-1 for lung cancer was much than CEA,CA125,NSE,SCC and Cyfer21.Moreover in theⅠstage patients,sensitive than the combination of the above five markers(70.8% vs 50.0%).Conclusion MIC-1 may be a new serum marker for lung cancer.It shows a good application prospect in lung cancer,especially in the early stage of lung cancer.

Objective To investigate the clinical value of macrophage inhibitory cytokine-1(MIC-1)in the diagnosis,early diagnosis,and treatment monitoring of pancreatic cancer.Methods serum samples form 522 patients with different clinical stages of pancreatic cancer,115 patients with benign pancreatic tumor,21 patients with chronic pancreatitis and 200 healthy persons were analyzed by self-made MIC-1 assay kit.And the patients at early stage were followed up.CEA and CA19-9 were analyzed by Roche Cobas 601 ECL analyzer and compared with MIC-1.Results The MIC-1 level in pancreatic cancer patients was significantly higher than that in benign tumor,chronic pancreatitis and normal control(1755.12±1112.23,863.56±508.24*,1264.35±751.09,391.56±299.55**,*P<0.001,**P=0.040).Area under the ROC curve of MIC-1,CA19-9 and CEA in diagnosis of pancreatic cancer was 0.945,0.836 and 33.3%,respectively.As the specificity was stayed in 97%,the sensitivity of MIC-1,CA19-9 and CEA of the pancreatic cancer was 73.9%,61.9% and 33.3%,respectively.MIC-1(77.9%)was more sensitive than CA19-9 and CEA(52.9% and 27.9%)in patients with early pancreatic cancer(phase Ⅰ+Ⅱ).Combined detection of CA19-9 and MIC-1 increased the sensitivity from 61.9%(CA19-9 alone)to 89.3%,which was significantly better than detection of MIC-1,CEA and CA19-9 alone.Serum levels of MIC-1 in patients with early pancreatic cancer decreased significantly after surgical treatment(P<0.001),while it significantly increased after tumer developed(P<0.001).Conclusion MIC-1 is a new and effective biomarker in serum for the diagnosis of pancreatic cancer.It is valuable in improving early diagnosis and monitoring clinical response.

Objective To investigate the clinical value of macrophage inhibitory cytokine-1(MIC-1)in diagnosis,early diagnosis,treatment monitoring and recurrence warning of colorectal cancer.Methods Serum samples form 239 patients with different clinical stages of colorectal cancer,16 patients with benign bowel disease and 200 healthy human were detected by self-made MIC-1 assay kit for MIC-1 level.And some of tumor patients are followed up.CEA and CA19-9 were analyzed by Roche Cobas 601 ECL analyzer.Results MIC-1 level in colorectal cancer patients was significantly higher than that in benign disease patients and normal control(1138.16 ± 857.46,486.76 ± 220.93,391.56 ± 299.55,P<0.001).Serum levels of MIC-1 showed an increasing trend in different clinical stages of colorectal cancer.MIC-1 have more sensitivity than CEA in patients with early colorectal cancer(stage Ⅰ:28.0% vs 8.0%;stage Ⅱ:42.7% vs 34.7%).Combined detection of CEA and MIC-1 increased the sensitivity from 42.3% of CEA to 64.4%,which was significantly better than the detection of MIC-1,CEA and CA19-9 alone.Serum levels of MIC-1 decreased significantly after effective treatment(P<0.001),and significantly increased at recurrence(P<0.001).Conclusion MIC-1 is a new and effective colorectal cancer biomarker in serum for the diagnosis of colorectal cancer.it is valuable in improving early diagnosis and monitoring clinical response.