单中心卵巢畸胎瘤患者中合并抗N-甲基-D-天冬氨酸受体脑炎的比例调查及临床特征分析

目的 探究卵巢畸胎瘤患者中发生抗N-甲基-D-天冬氨酸受体（NMDAR）脑炎的比例,并将合并抗NMDAR脑炎的卵巢畸胎瘤患者与未合并抗NMDAR脑炎的卵巢畸胎瘤患者的临床特征进行总结对比。方法 收集卵巢畸胎瘤患者的临床资料,将其分为合并抗NMDAR脑炎组与未合并抗NMDAR脑炎组,对其临床特征进行对比分析。结果 共收集到168例卵巢畸胎瘤患者,其中14例（8.3%）合并抗NMDAR脑炎;合并抗NMDAR脑炎的卵巢畸胎瘤患者年龄低于未合并抗NMDAR脑炎的卵巢畸胎瘤患者[（23.8±5.5）岁 vs. （29.8±9.1）岁,P = 0.016]。合并抗NMDAR脑炎的卵巢畸胎瘤患者肿瘤标志物以癌抗原125及血清铁蛋白升高为主,而未合并抗NMDAR脑炎的卵巢畸胎瘤患者肿瘤标志物以糖类抗原199升高为主。合并抗NMDAR脑炎与未合并抗NMDAR脑炎的卵巢畸胎瘤患者的肿瘤组织均可含有神经组织。结论 卵巢畸胎瘤患者中发生抗NDMAR脑炎的比例不低,对于无明显症状的卵巢畸胎瘤患者,可考虑积极行手术治疗,以降低发生抗NMDAR脑炎的风险。     

Targeting autophagy in colorectal cancer: An update on pharmacological small-molecule compounds

Autophagy, an evolutionarily highly conserved cellular degradation process, plays the Janus role (either cytoprotective or death-promoting) in colorectal cancer, so the targeting of several key autophagic pathways with small-molecule compounds may be a new therapeutic strategy. In this review, we discuss autophagy-associated cell death pathways and key cytoprotective autophagy pathways in colorectal cancer. Moreover, we summarize a series of small-molecule compounds that have the potential to modulate autophagy-associated cell death or cytoprotective autophagy for therapeutic purposes. Taken together, these findings demonstrate the Janus role of autophagy in colorectal cancer, and shed new light on the exploitation of a growing number of small-molecule compounds to target autophagy in future cancer drug discovery.     

利用蛋白质组学技术筛选特发性肺间质纤维化患者血清生物标志物

目的 利用蛋白质组学技术筛选并鉴定特发性肺间质纤维化患者和健康人血清差异表达蛋白。方法 收集山东大学第二医院于2014年10月至2015年10月收治的30例特发性肺间质纤维化患者及健康人血清各30份,组内等量混合后,去除高丰度蛋白,经同位素标记相对和绝对定量试剂标记后采用二维液相色谱-串联质谱鉴定并进行相对定量。对鉴定出的差异蛋白进行基因功能聚类（GO）分析和通路富集分析,筛选出与特发性肺间质纤维化发生相关的蛋白质。结果 质谱鉴定出置信度>95%的蛋白质共490个,其中差异表达蛋白25个。与对照组相比,25个差异蛋白中有4个表达上调,21个表达下调。GO分析显示,大多数差异蛋白处于细胞外区域（92%）;通路富集分析显示,含差异蛋白数量最多的通路为补体和凝血级联通路。结论 特发性肺间质纤维化患者血清中鉴定出了与补体及凝血相关的差异蛋白,其具体功能有待进一步研究。     

A Food-Derived Dietary Supplement Containing a Low Dose of Iron Improved Markers of Iron Status Among Nonanemic Iron-Deficient Women

Objective: Iron deficiency is the most common nutrient deficiency in the world. While deficiency can often be resolved through dietary supplementation with iron, adverse events are common and frequently preclude compliance. The objective of this study was to determine whether a food-derived dietary supplement containing a low dose of iron and nutrients that increase iron absorption could resolve iron deficiency with fewer adverse events than reported at higher doses.

Methods: A pilot clinical trial (NCT02683369) was conducted among premenopausal women with nonanemic iron deficiency that was verified by blood screening. Participants consumed a dietary supplement (Blood Builder®/Iron Response®) once daily for 8 weeks containing 26 mg of iron, vitamin C, folate, and other food-derived nutrients. Primary outcomes were markers of iron status (serum ferritin, hemoglobin, soluble transferrin receptor, total body iron stores) and secondary outcomes were self-reported fatigue and energy. All outcomes were assessed at baseline and 8 weeks. Adverse events were monitored with questionnaires, daily diaries, and contact with a physician. Dependent samples t test and Wilcoxon signed-rank test were used to analyze outcomes.

Results: Twenty-three participants enrolled in the study. Iron deficiency was resolved in the sample (mean serum ferritin: baseline = 13.9 μg/L, 8 weeks = 21.1 μg/L, p < 0.001). All other markers of iron status, fatigue, and energy also improved during the study (p < 0.04). No adverse events were reported. Conclusions: While larger and controlled studies are needed to confirm these findings, a food-derived dietary supplement with a low dose of iron and absorption-enhancing nutrients resolved iron deficiency and improved all other markers of iron status without any adverse events.     

妊娠肥胖和妊娠期糖尿病患者血清脂肪因子水平变化及其影响因素分析

目的观察妊娠肥胖和妊娠期糖尿病(GDM)患者血清脂肪因子水平变化及其影响因素。方法随机选择2016年7月-2017年7月在该院进行产检的妊娠肥胖、GDM以及正常孕妇各60例进行临床研究,分别作为妊娠肥胖组、GDM组和对照组。所有来检人员均给予生化指标和脂肪因子进行检查,比较3组孕妇上述生化指标是否有统计学差异。对血清脂肪因子水平和生化指标进行相关性检验,分析血清脂肪因子水平与生化指标之间的相关性和影响其异常的因素。结果3组孕妇生化指标中总胆固醇(TC)差异无统计学意义(P>0.05),FPG、TG、HDL-C、LDL-C、FINS、HOMA-IR差异均有统计学意义(P<0.05);3组孕妇血清脂肪因子RBP-4、APN、TNF-α、VF差异均有统计学意义(P<0.05),妊娠肥胖组和GDM组的APN低于对照组,其余指标均高于对照组。对3组孕妇的生化指标和血清脂肪因子使用PeaRson相关性分析进行统计,结果发现,TNF-α与孕妇的FPG、TG、FINS、HOMA-IR呈正相关(P<0.05);APN水平与孕妇HDL-C呈正相关(P<0.05),与FPG、FINS、NOMA-IR呈负相关(P<0.05);RBP-4水平与FINS、NOMA-IR呈正相关(P<0.05);VF水平与孕妇FPG、FINS、NOMA-IR呈正相关(P<0.05),其余无相关性(P>0.05)。结论妊娠肥胖和GDM与患者的血清因子水平变化之间具有密切联系,RBP-4、APN、TNF-α、VF等因子的变化可能导致患者相关生化指标发生变化,也同时导致患者妊娠肥胖、GDM等妊娠疾病的发生。     

Endoscopic molecular imaging of early gastric cancer using fluorescently labeled human H-ferritin nanoparticle

Optical imaging technologies improve clinical diagnostic accuracy of early gastric cancer (EGC). However, there was a lack of imaging agents exhibiting molecular specificity for EGCs. Here, we employed the dye labeled human heavy-chain ferritin (HFn) as imaging nanoprobe, which recognizes tumor biomarker transferrin receptor 1 (TfR1), to enable specific EGC imaging using confocal laser endomicroscopy (CLE). TfR1 expression was initially examined in vitro in gastric tumor cells and in vivo through whole-body fluorescence and CLE imaging in tumor-bearing mice. Subsequently, dye labeled HFn was topically applied to resected human tissues for EGC detection. CLE analysis of TfR1-targeted fluorescence imaging allowed distinction of neoplastic from non-neoplastic tissues (P?<?0.0001), and TfR1 expression level was found to correlate with EGC differentiation degrees (P?<?0.0001). Notably, the CLE evaluation correlated well with the immunohistochemical findings (κ-coefficient: 0.8023). Our HFn-nanoprobe-based CLE increases the accuracy of EGC detection and enables visualization of tumor margins and endoscopic resection.     

富含半胱氨酸蛋白61在结直肠癌中的应用

目的通过测定结直肠癌(colorectal cancer,CRC)患者血清富含半胱氨酸蛋白61(cysteine-rich Protein 61,Cyr61)水平,分析其用于结直肠癌诊断和病理评估的价值。方法用ELISA方法检测血清Cyr61浓度,再用ROC曲线计算最佳灵敏度和特异性,比较Cyr61在诊断结直肠癌的效果;分析Cyr61水平与结直肠癌TNM分期及淋巴结转移的关系,探究血清Cyr61水平与结直肠癌临床病理分期的关系。结果 CRC患者的血清Cyr61水平明显高于健康对照组(P<0.05),血清Cyr61、CEA和CA19-9检测对诊断结直肠癌的灵敏度分别为70.2%、48.2%和48.9%,Ⅲ-Ⅳ期血清Cyr61表达高于Ⅰ-Ⅱ期,有淋巴结转移的血清Cyr61表达高于无淋巴结转移。结论血清Cyr61水平可作为CRC诊断的潜在标志物,且与肿瘤分期和淋巴结转移有关,血清Cyr61水平对结直肠癌的监测有重要意义。     

食管癌患者血清铁蛋白、红细胞分布宽度和红细胞沉降率水平的差异分析及预后评估

目的分析血清铁蛋白(serum ferritin,SF)、红细胞分布宽度(redblood cell distribution width,RDW)和红细胞沉降率(erythrocyte sedimentation rate,ESR)在食管癌诊断及预后中的价值。方法收集四川省林业中心医院收治的食管癌患者140例,反流性食管炎患者92例,同期收集健康人群140例。采用血液分析仪检测外周全血RDW,采用化学发光法检测血清SF水平,采用魏氏法检测ESR值。结果与反流性食管炎(SF:168.7±16.8μg/L;RDW:13.4±2.3%;ESR:15.3±2.6mm/h)和健康对照(SF:160.3±15.5μg/L;RDW:12.7±2.1%;ESR:15.6±2.8mm/h)相比,SF、RDW和ESR水平在食管癌(SF:321.5±37.1μg/L;RDW:22.5±3.0%;ESR:27.5±7.8mm/h)患者中均显著升高(P<0.05)。Spearman相关性分析显示,SF、RDW和ESR水平与TNM分期(SF:r=0.327,P<0.001;RDW:r=0.264,P=0.002;ESR:r=0.283,P=0.001)均呈线性关联,且三者的水平在Ⅲ~Ⅳ期患者中最高,但SF、RDW和ESR水平与组织学类型均无显著相关性(SF:r=0.012,P=0.884;RDW:r=-0.119,P=0.160;ESR:r=-0.018,P=0.834)。ROC结果显示,联合SF、RDW和ESR在鉴别食管癌与反流性食管炎和健康对照的曲线下面积(area under ROC curve,AUC)为0.923(95%CI:0.893~0.974,P<0.001),灵敏度为92.3%,特异性为83.4%。生存分析显示,相比低SF组和低RDW组,高SF组(χ^2=15.366,P<0.001)和高RDW组(χ^2=6.012,P=0.014)生存率显著降低,而低ESR组和高ESR组间生存率差异无统计学意义(χ^2=1.695,P=0.193)。结论联合SF、RDW和ESR对食管癌的诊断及发病风险评估具有价值,且SF和RDW在食管癌预后评价中有重要意义。