血浆代谢轮廓分析在慢性肾脏病早期诊断中的应用价值

摘要 目的：探究血浆代谢轮廓分析在慢性肾脏病早期诊断中的应用价值。方法：选取我院在2019-2021收治的120例慢性肾病（CKD）患者,运用相色谱-四级杆飞行时间质谱（liquid chromatography quadrupole time-of-flight mass spectrometry,LC-QTOF/MS）联用技术对参与本次研究的患者的血浆样品进行非靶向代谢组学分析,判断不同时期慢性肾病患者与健康对照者的血浆代谢轮廓谱,同时利用多变量结合单变量统计分析方法筛选差异代谢物。结果：慢性肾脏病（CKD）肌酐、尿酸、尿素、血红蛋白等检测物质多项生化指标异常,且据统计分析可知,在不同阶段CKD患者的血浆中找到了多种差异化合物,其中磺基丙氨鞘酸、氨醇-１-磷酸、醛固酮差异显著。结论：研究证明血浆代谢轮廓分析可以增进对慢性肾病发病机制的了解,为之后早期诊断慢性肾病具有重大意义,值得推广与应用。     

老年非小细胞肺癌患者全身免疫-炎症指数与化疗预后的相关性分析

摘要 目的：探讨老年非小细胞肺癌患者全身免疫-炎症指数与化疗预后的相关性。方法：回顾性选择2018年1月至2020年5月确诊的老年非小细胞肺癌患者60例。收集60例老年非小细胞肺癌患者的年龄、性别、吸烟、病理分型、病理分期、入院的血红蛋白、C反应蛋白、乳酸脱氢酶、神经元特异性烯醇化酶、D二聚体、癌胚抗原、中性粒细胞计数、血小板计数、淋巴细胞计数、单核细胞计数等指标。（1）比较不同低全身免疫-炎症指数老年非小细胞肺癌患者的临床特征资料;（2）计算高全身免疫-炎症指数与低全身免疫-炎症指数组的中位无进展生存期;（3）Cox单因素分析模型分析老年非小细胞肺癌患者化疗中位无进展生存期的影响因素;（4）分析老年非小细胞肺癌患者化疗预后与全身免疫-炎症指数、肿瘤分期、淋巴细胞计数、癌胚抗原的相关性。结果：高、低全身免疫-炎症指数两组在肿瘤分期、血红蛋白、C反应蛋白、乳酸脱氢酶、中性粒细胞计数、血小板计数、单核细胞计数、淋巴细胞计数、D二聚体、癌胚抗原对比上有统计学意义（P<0.05）。低全身免疫-炎症指数组的化疗中位无进展生存期明显优于高全身免疫-炎症指数组（P<0.05）。Cox多因素分析结果表明,肿瘤分期在Ⅲ~Ⅳ期、淋巴细胞计数<1.1×10⁹/L、癌胚抗原≥1 ng/mL、全身免疫-炎症指数≥18.172是老年非小细胞肺癌患者化疗中位无进展生存期的独立危险因素（P<0.05）。Sperman相关性分析结果表明,老年非小细胞肺癌患者化疗预后与全身免疫-炎症指数呈正相关（r=0.525,P=0.038）。结论：全身免疫-炎症指数是影响老年非小细胞肺癌患者化疗预后的独立危险因素,其升高则提高预后患者的预后不良。     

EGFR突变与替莫唑胺联合IGRT大分割放射治疗非小细胞肺癌脑转移瘤疗效的相关性

摘要 目的：研究表皮生长因子受体（EGFR）突变对替莫唑胺联合图像引导大分割放射（IGRT）治疗非小细胞肺癌脑转移瘤临床疗效的影响。方法：选择2015年1月到2018年12月在我院接受治疗的非小细胞肺癌脑转移患者86例,根据是否出现EGFR突变分为对照组（EGFR未突变组）和研究组（EGFR突变组）,每组43人,两组患者均接受替莫唑胺联合IGRT大分割放射治疗。比较两组患者临床治疗疗效、不良反应发生情况、复发时间、生存时间和生活质量。结果：研究组患者临床治疗总有效率较对照组患者高（P<0.05）。研究组患者治疗后复发时间和生存时间均显著高于对照组患者（P<0.05）。两组患者治疗期间头痛、恶心、疲乏以及神经毒性等不良反应的发生情况比较无显著差异（P>0.05）。两组患者治疗前生活质量KarnofSky活动状态评分（KPS）和肺癌相关症状量表（LCSS评分）无显著差异（P>0.05）;治疗后,研究组患者KPS评分显著高于对照组（P<0.05）,而LCSS评分显著低于对照组患者（P<0.05）。结论：替莫唑胺联合IGRT大分割放射治疗EGFR突变的非小细胞肺癌脑转移瘤临床疗效更好,并且治疗后患者生活质量更优。     

糖尿病对射血分数保留心力衰竭患者血生化指标、心脏指标及生活质量的影响

摘要 目的：探讨糖尿病（DM）对射血分数保留心力衰竭（HFpEF）患者血生化指标、心脏指标及生活质量的影响。方法：选取2017年1月-2019年5月我院收治的246例HFpEF患者作为研究对象,根据是否并发DM分为DM-HFpEF组（n=98）和NDM-HFpEF组（n=148）,比较两组患者基线资料、血生化指标,采用超声心动图检测心功能参数,采用明尼苏达心力衰竭生活质量调查表（MLHFQ）评价患者的生活质量。结果：两组患者体重、收缩压、合并冠心病比例、合并高血压比例相比较,差异有统计学意义（P＜0.05);与NDM-HFpEF组患者相比,DM-HFpEF组患者白细胞计数（WBC）、中性粒细胞计数（N）、血肌酐（Scr）、甘油三酯（TG）、空腹血糖（FBG）、餐后两小时血糖（2hPBG）、K⁺水平升高,血红蛋白（Hb）、高密度脂蛋白胆固醇（HDL-C）水平降低（P＜0.05);DM- HFpEF组舒张末期左心室容积指数（LVEDVI）低于NDM-HFpEF组患者,室间隔厚度(IVS)、左心室后壁厚度（PWTD）、E峰、E/e''高于NDM-HFpEF组患者,差异有统计学意义（P＜0.05);DM- HFpEF组患者MLHFQ中体力限制、社会限制、情绪、经济维度评分及总分高于NDM-HFpEF组患者,差异有统计学意义（P＜0.05)。结论：DM促进了HFpEF患者IVS、PWTD的增厚,降低了心脏舒张功能和患者的生活质量,且明显加重了HFpEF患者血糖血脂的代谢紊乱。     

外周血CTC、VEGF的水平与晚期非小细胞肺癌临床特征及化疗疗效关系的研究

摘要 目的：探讨外周血循环肿瘤细胞（CTC）、血管内皮生长因子（VEGF）的水平与晚期非小细胞肺癌临床特征及化疗疗效的关系。方法：选取我院2017年1月到2020年1月收治的80例晚期非小细胞肺癌患者作为研究对象,所有患者均采取一线方案化疗,分析外周血CTC、VEGF的水平与患者的年龄、性别等的关系,并对晚期非小细胞肺癌化疗疗效进行单因素与多因素COX分析。结果：CTC、VEGF与不同性别、年龄患者和TNM分期无明显关系（P＞0.05）,与淋巴结转移、肿瘤分化程度、肿瘤大小有关（P＜0.05）;80例患者中,客观缓解率（ORR）为51.25 %（41/80）,疾病控制率（DCR）为71.25 %（57/80）;淋巴结转移、肿瘤分化程度、CTC和血清VEGF水平为晚期非小细胞肺癌患者ORR、DCR的影响因素（P＜0.05）;COX分析分析表明：肿瘤中、低分化、CTC阴性、VEGF降低为晚期非小细胞肺癌化疗ORR和DCR提升的独立影响因素（P＜0.05）。结论：外周血CTC、VEGF检测对于晚期非小细胞肺癌化疗近远期疗效评估具有重要价值,属于预后独立影响因素。因此,CTC、VEGF可作为晚期非小细胞肺癌的预后及疗效判断的指标。     

PD-1/PD-L1抑制剂对肺鳞状细胞癌患者调节性T细胞及其亚型的影响

摘要 目的：探讨PD-1/PD-L1抑制剂对肺鳞状细胞癌（鳞癌）患者调节性T细胞（Regulatory T cell，Treg细胞）及其亚型的影响。方法：2019年1月至2020年12月来我院就诊的肺鳞癌初诊患者纳入本项研究；患者均接受Nivolumab治疗，根据治疗效果不同，将患者分为缓解组（n=20）和无效组（n=20）；流式细胞术检测外周血总Treg细胞、PD-1+Treg细胞、CD150+Treg细胞、CTLA-4+Treg细胞、LAG-3+Treg细胞的比例。结果：缓解组外周血总Treg细胞、CTLA-4+Treg细胞和LAG-3+Treg细胞的比例分别为4.052±0.231%、1.616±0.099%和0.328±0.021%，无效组的比例分别为5.532±0.395%、3.277±0.224%和0.857±0.108%，差异均具有显著的统计学意义（t=3.239，P=0.009；t=6.776，P＜0.001；t=4.807，P＜0.001）；缓解组外周血PD-1+Treg细胞和CD150+Treg细胞的比例分别为0.195±0.016%和1.530±0.113%，无效组的比例分别为0.203±0.018%和1.787±0.157%，差异均不具有统计学意义（t=0.318，P=0.757；t=1.329，P=0.214）。结论：PD-1/PD-L1抑制剂治疗无效的肺鳞癌患者外周血总Treg细胞、CTLA-4+Treg细胞和LAG-3+Treg细胞的比例均显著升高。     

APP/PS1小鼠中PEG-PLA纳米粒的表面蛋白冠组成及其脑内递送的实验研究

摘要 目的：研究阿尔茨海默病（Alzhemer''s disease,AD）模型鼠中聚乙二醇聚乳酸（poly(ethylene glycol)-poly(l-lactide),PEG-PLA）纳米粒表面蛋白冠组成及其对脑内递送特性的影响。方法：制备PEG-PLA纳米粒,测定纳米粒的zeta电位及粒径,采用透射电子显微镜观察纳米粒形态。通过双光子显微镜观察APP/PS1小鼠与野生型（Wild Type,WT）小鼠脑内PEG-PLA纳米粒分布特性。采用液相色谱-质谱联用（LC-MS）技术对PEG-PLA纳米粒分别与APP/PS1小鼠和WT小鼠血浆孵育形成的两种不同蛋白冠进行蛋白组学分析。结果：制备的PEG-PLA纳米粒粒径均一,分散性较好。静脉注射PEG-PLA后,APP/PS1小鼠脑内纳米粒量明显高于WT小鼠。蛋白质组学结果显示,APP/PS1小鼠血浆孵育组PEG-PLA纳米粒表面蛋白冠中凝聚素（Clusterin）明显高于WT小鼠血浆孵育组,该蛋白与纳米粒逃避机体清除有关。此外,纳米粒蛋白冠中血管性血友病因子（Von Willebrand factor）、玻连蛋白（Vitronectin）、肌球蛋白重链-9（Myosin-9）等参与细胞粘附作用相关蛋白在APP/PS1小鼠血浆孵育组也明显多于WT小鼠血浆孵育组。结论：PEG-PLA纳米粒在AD模型小鼠中表现出的高入脑量,可能与AD疾病影响纳米粒蛋白冠组成有关。     

肺鳞状细胞癌和腺癌PD-L1蛋白及相关miRNA表达差异的研究

摘要 目的：探讨肺鳞状细胞癌（鳞癌）和腺癌PD-L1蛋白及相关miRNA表达的差异。方法：2019年5月至2020年11月来我院就诊的非小细胞肺癌初治患者纳入本项研究；按照病理类型，将患者分为腺癌组和鳞癌组；H&E染色检测免疫细胞数量；免疫组化检测PD-L1、ki-67、PD-1、CTLA-4和LAG-3的表达；miRNA测序筛选鳞癌和腺癌间差异表达的miRNA。结果：H&E染色结果显示鳞癌组微环境中免疫细胞的数量为86.86±8.96个/高倍视野（HPF），腺癌组的数量为26.29±3.99个/HPF（t=6.173，P＜0.001）；肺鳞癌组微环境免疫细胞PD-1、CTLA-4和LAG-3阳性表达的比例分别为53.71±6.88%、35.29±3.25%和34.43±3.29%，腺癌组阳性表达的比例分别为22.29±3.80%、13.43±2.32%和24.00±1.98%（t=3.997，P=0.002；t=5.476，P＜0.001；t=2.719，P=0.019）；肺鳞癌组患者PD-L1蛋白阳性表达的比例为76.67%，腺癌组的比例为36.67%（P=0.001）；肺鳞癌PD-L1（miR-135、miR-24和miR-30b等）和PD-1（miR-802、miR-155和miR-3127-5p等）相关miRNA的表达均显著高于腺癌。结论：肺鳞癌PD-L1蛋白及相关miRNA的表达、微环境免疫细胞PD-1、CTLA-4和LAG-3阳性比例均显著高于腺癌。     

心脏再同步治疗对非缺血性心肌病患者心肌胶原代谢的影响

摘要 目的：探讨心脏再同步治疗（CRT）对非缺血性心肌病（NICM）患者心肌胶原代谢的影响。方法：选取NICM患者76例,其中仅接受标准药物治疗者26例（Control组）,接受CRT及标准药物治疗者50例（CRT组）。分别于基线、6月及12月检测外周血中心肌胶原代谢的标记物I型胶原羧基末端前肽（PICP）、I型胶原羧基端肽（ICTP）、基质金属蛋白酶-1（MMP-1）及组织金属基质蛋白酶抑制剂-1（TIMP-1）的变化。随访12月时左室射血分数（LVEF）值与基线比较净值增长5 %定义为患者临床治疗有反应。结果：与基线比较,CRT组患者术后6月、12月PICP、ICTP及MMP-1均明显降低（P均<0.05）;Control组患者术后6月、12月PICP、ICTP、MMP-1及TIMP-1与基线比较均未显示统计学差异。40例(53 %)患者临床治疗有反应,其中CRT组33例（67 %）明显高于Control组7例（27 %）,两组间具有统计学差异（P=0.01）。多因素logistics回归分析显示QRS间期,LVEF,PICP为临床反应预测因子。结论：CRT可以降低NICM患者的心肌胶原合成和分解,减缓心肌纤维化;检测患者基线PICP可预测患者治疗的临床反应,为NICM的临床诊治提供一定的参考价值。     

康莱特注射液联合GP方案对晚期非小细胞肺癌患者免疫功能、新生血管生成和血清JAK2/STAT3信号通路的影响

摘要 目的：探讨康莱特注射液联合吉西他滨联合顺铂（GP）方案对晚期非小细胞肺癌（NSCLC）患者免疫功能、新生血管生成和血清两面神激酶2（JAK2）/信号转导及转录活化因子3（STAT3）信号通路的影响。方法：选取2019年2月至 2020年2月期间湖南省中医药研究院附属医院收治的80例晚期NSCLC患者。根据随机数字表法分为对照组（GP化疗,n=40）和观察组（康莱特注射液联合GP化疗,n=40）,治疗后观察两组患者疗效、免疫功能、新生血管生成指标、JAK2/STAT3信号通路相关指标的变化,记录不良反应发生率,并随访2年观察患者生存预后情况。结果：对照组、观察组的临床总有效率分别为60.00%（24/40）、82.50%（33/40）,组间对比有统计学差异（P>0.05）。与对照组相比,观察组治疗后的CD8⁺更低,CD3⁺、CD4⁺、CD4⁺/CD8⁺更高（P<0.05）。与对照组相比,观察组治疗后的血管内皮生长因子（VEGF）进一步下降,组织抑制因子-2（TIMP-2）进一步升高（P<0.05）。与对照组相比,观察组治疗后的JAK2mRNA、STAT3mRNA进一步下降（P<0.05）。两组不良反应发生率组间对比,统计学无差异（P>0.05）。观察组中位生存期为19个月明显长于对照组的10个月,差异有统计学意义（P<0.05）。结论：康莱特注射液联合GP方案用于晚期NSCLC患者,可在一定程度上阻止疾病进展,减轻免疫抑制,延长生存期,考虑可能与下调JAK2/STAT3信号通路有关。     

血清细胞角蛋白19、神经元特异性烯醇化酶及鳞状上皮细胞癌抗原在小细胞肺癌诊断及病情评估中的作用研究

摘要 目的：分析血清细胞角蛋白19（CK19）、神经元特异性烯醇化酶（NSE）及鳞状上皮细胞癌抗原（SCCA）在小细胞肺癌诊断及病情评估中的作用。方法：选择我院自2020年1月至2022年7月收治的85例小细胞肺癌患者作为观察组,另选同期的85例肺部良性疾病患者作为对照组。检测两组血清CK19、NSE、SCCA表达水平,比较两组血清CK19、NSE、SCCA表达水平及其阳性率,使用ROC曲线下面积（AUC）分析上述指标对小细胞肺癌的诊断效能,观察小细胞肺癌不同分期患者血清CK19、NSE、SCCA表达水平的差异性,分析观察组治疗前后血清CK19、NSE、SCCA表达水平的变化情况。结果：观察组血清CK19、NSE、SCCA表达水平均较对照组高（P＜0.05）;观察组血清CK19、NSE和SCCA的阳性率均较对照组高（P＜0.05）;经ROC曲线分析,血清CK19、NSE联合SCCA诊断小细胞肺癌的敏感度为91.23 %,特异度为84.67 %,AUC为0.910;在85例小细胞肺癌患者中,临床分期为局限期33例、广泛期52例;广泛期患者血清CK19、NSE、SCCA表达水平均高于局限期患者（P＜0.05）。结论：血清CK19、NSE联合SCCA诊断小细胞肺癌的效能较好,三者均与患者病情严重程度有关,有利于此病的早期诊断和病情评估,值得进一步研究应用。     

Metabolic signatures of four major histological types of lung cancer cells

Introduction

Histologically lung cancer is classified into four major types: adenocarcinoma (Ad), squamous cell carcinoma (SqCC), large cell carcinoma (LCC), and small cell lung cancer (SCLC). Presently, our understanding of cellular metabolism among them is still not clear.

Objectives

The goal of this study was to assess the cellular metabolic profiles across these four types of lung cancer using an untargeted metabolomics approach.

Methods

Six lung cancer cell lines, viz., Ad (A549 and HCC827), SqCC (NCl-H226 and NCl-H520), LCC (NCl-H460), and SCLC (NCl-H526), were analyzed using liquid chromatography quadrupole time-of-flight mass spectrometry, with normal human small airway epithelial cells (SAEC) as the control group. The principal component analysis (PCA) was performed to identify the metabolic signatures that had characteristic alterations in each histological type. Further, a metabolite set enrichment analysis was performed for pathway analysis.

Results

Compared to the SAEC, 31, 27, 34, 34, 32, and 39 differential metabolites mainly in relation to nucleotides, amino acid, and fatty acid metabolism were identified in A549, HCC827, NCl-H226, NCl-H520, NCl-H460, and NCl-H526 cells, respectively. The metabolic signatures allowed the six cancerous cell lines to be clearly separated in a PCA score plot.

Conclusion

The metabolic signatures are unique to each histological type, and appeared to be related to their cell-of-origin and mutation status. The changes are useful for assessing the metabolic characteristics of lung cancer, and offer potential for the establishment of novel diagnostic tools for different origin and oncogenic mutation of lung cancer.

     

Plasma-free amino acid profiling of cervical cancer and cervical intraepithelial neoplasia patients and its application for early detection

In this study, plasma-free amino acid profiles were used to investigate pre-cancerous cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) metabolic signatures in plasma. Additionally, the diagnostic potential of these profiles was assessed, as well as their ability to provide novel insight into CSCC metabolism and systemic effects. Plasma samples from CIN patients (n = 26), CSCC patients (n = 22), and a control healthy group (n = 35) were analyzed by high-performance liquid chromatography, and their spectral profiles were subjected to the t test for statistical significance. Potential metabolic biomarkers were identified using database comparisons that examine the significance of metabolites. Compared with healthy controls, patients with CIN and CSCC demonstrated lower levels of plasma amino acids; plasma levels of arginine and threonine were increased in CIN patients but were decreased in cervical cancer patients. Additionally, the levels of a larger group of amino acids (aspartate, glutamate, asparagine, serine, glycine, histidine, taurine, tyrosine, valine, methionine, lysine, isoleucine, leucine, and phenylalanine) were gradually reduced from CIN to invasive cancer. These findings suggest that plasma-free amino acid profiling has great potential for improving cancer screening and diagnosis and for understanding disease pathogenesis. Plasma-free amino acid profiles may have the potential be used to determine cancer diagnoses in the early stage from a single blood sample and may enhance our understanding of its mechanisms.     

MCM6、MCM7、KIAA1522蛋白联合检测对非小细胞肺癌诊断及预后预测的临床价值研究

摘要 目的：筛选肺癌蛋白分子标志物,寻找可诊断及预测肺癌预后的蛋白标志物。方法：选择2014年8月~2019年7月于西安市第四医院确诊并进行肺部切除手术的非小细胞肺癌(non-small-cell lung Cancer,NSCLC)患者80例,采用免疫组织化学(immunohistochemistry,IHC)检测NSCLC患者肺癌组织标本和癌旁MCM2(Minichromosome maintenance protein2, 微小染色体维持蛋白2)、MCM5(Minichromosome maintenance protein5,微小染色体维持蛋白5)、MCM6(Minichromosome maintenance protein6,微小染色体维持蛋白6)、MCM7(Minichromosome maintenance protein7,微小染色体维持蛋白7)、KIAA1522和KIAA0317蛋白表达阳性率,探讨多蛋白联合检测对NSCLC诊断及预后预测的临床应用价值。结果：肺癌组织中MCM2、MCM5、MCM6、MCM7、KIAA1522和KIAA0317的阳性表达率均显著高于癌旁正常肺组织(P＜0.05),其中MCM6、MCM7和KIAA1522在50 %以上;以MCM6、MCM7、KIAA15223蛋白联合检测肺癌组织,不同性别、不同年龄、类型和分期的NSCLC患者的联合蛋白阳性率无统计学差异(P＞0.05),且蛋白阳性率均大于80 %;MCM7高表达较之低表达或不表达的病例,显著增加患者的死亡风险(P=0.000)。男性(P=0.031)、III~IV期患者(P＜0.001)、以及低分化程度(P=0.012)也是患者的不良预后因素,多因素回归分析显示,MCM7是一个独立的预测指标(P=0.000), 与患者生存具有显著相关性,对预后有一定的预测作用。结论：NSCLC患者肺癌组织中MCM6、MCM7和KIAA1522呈高表达,三者联合检测对NSCLC的检测具有较高的准确性、敏感性和特异性,高水平的MCM7表达提示肺癌患者的不良预后。     

Cell-free DNA as a prognostic marker in stage I non-small-cell lung cancer patients undergoing stereotactic body radiotherapy

Abstract

Objective: To evaluate whether plasma cell-free DNA (cfDNA) was related to clinical outcome in inoperable stage I non-small cell lung cancer (NSCLC) patients undergoing stereotactic body radiotherapy (SBRT).

Materials and methods: Plasma cfDNA was assessed at baseline, before the last day and 45 days after the end of SBRT, in 22 NSCLC patients. Twenty-two healthy controls were also evaluated.

Results: Plasma cfDNA was higher in patients than in controls. An association with unfavourable disease-free survival was found for continuous baseline cfDNA increments (HR?=?5.9, 95%CI: 1.7–19.8, p?=?0.04).

Conclusion: Plasma cfDNA may be a promising prognostic biomarker in high-risk NSCLC patients.     

α-核突触蛋白基因突变小鼠脑组织中内源性代谢产物的变化

目的:明确α-核突触蛋白与帕金森病的病理生理相关性及其临床意义。方法:采用相色谱-质谱联用(UPLC-MS)检测野生型小鼠和基因突变型小鼠脑组织中内源性代谢性产物,通过mzcloud法对小鼠脑组织中内源性代谢物质进行鉴定,将相应数据进行主成分分析(PCA)和聚类分析,分析其相关差异表达代谢物,并构建通路图和互作网络图。结果:(1)基于LC/MS法的代谢组分析结果显示两组间差异代谢物以氨基酸类及磷脂类等为主,包括β-丙氨酰-L-组氨酸、L-精氨酸、L-组氨酸、L-亮氨酸、L-苯丙氨酸、L-缬氨酸、L-天门冬氨酸、L-丙氨酸、磷脂酰胆碱等;(2)构建的代谢通路主要涉及酮体的合成和降解、牛磺酸和亚牛磺酸代谢、丙氨酸,天冬氨酸和谷氨酸代谢、精氨酸和脯氨酸代谢、组氨酸代谢、苯丙氨酸代谢、缬氨酸,亮氨酸和异亮氨酸的生物合成、甘油磷脂代谢等,从中发现18个具有标志性的代谢成分。结论:α-核突触蛋白基因突变后,酮体的合成和降解、牛磺酸和亚牛磺酸代谢、丙氨酸,天冬氨酸和谷氨酸代谢、精氨酸和脯氨酸代谢、组氨酸代谢、苯丙氨酸代谢、缬氨酸,亮氨酸和异亮氨酸的生物合成、甘油磷脂代谢等代谢通路发生了变化,涉及β-丙氨酰-L-组氨酸、L-精氨酸、L-组氨酸、L-亮氨酸、L-苯丙氨酸、L-缬氨酸、L-天门冬氨酸、L-丙氨酸、磷脂酰胆碱等的生物学标志性代谢产物变化。     

Promoting Help-Seeking in Response to Symptoms amongst Primary Care Patients at High Risk of Lung Cancer: A Mixed Method Study

BackgroundLung cancer symptoms are vague and difficult to detect. Interventions are needed to promote early diagnosis, however health services are already pressurised. This study explored symptomology and help-seeking behaviours of primary care patients at ‘high-risk’ of lung cancer (≥50 years old, recent smoking history), to inform targeted interventions.MethodsMixed method study with patients at eight general practitioner (GP) practices across south England. Study incorporated: postal symptom questionnaire; clinical records review of participant consultation behaviour 12 months pre- and post-questionnaire; qualitative participant interviews (n = 38) with a purposive sample.ResultsA small, clinically relevant group (n = 61/908, 6.7%) of primary care patients was identified who, despite reporting potential symptoms of lung cancer in questionnaires, had not consulted a GP ≥12 months. Of nine symptoms associated with lung cancer, 53.4% (629/1172) of total respondents reported ≥1, and 35% (411/1172) reported ≥2. Most participants (77.3%, n = 686/908) had comorbid conditions; 47.8%, (n = 414/908) associated with chest and respiratory symptoms. Participant consulting behaviour significantly increased in the 3-month period following questionnaire completion compared with the previous 3-month period (p = .002), indicating questionnaires impacted upon consulting behaviour. Symptomatic non-consulters were predominantly younger, employed, with higher multiple deprivation scores than their GP practice mean. Of symptomatic non-consulters, 30% (18/61) consulted ≤1 month post-questionnaire, with comorbidities subsequently diagnosed for five participants. Interviews (n = 39) indicated three overarching differences between the views of consulting and non-consulting participants: concern over wasting their own as well as GP time; high tolerance threshold for symptoms; a greater tendency to self-manage symptoms.ConclusionsThis first study to examine symptoms and consulting behaviour amongst a primary care population at ‘high- risk’ of lung cancer, found symptomatic patients who rarely consult GPs, might respond to a targeted symptom elicitation intervention. Such GP-based interventions may promote early diagnosis of lung cancer or other comorbidities, without burdening already pressurised services.     

Dynamic metabolic transformation in tumor invasion and metastasis in mice with LM-8 osteosarcoma cell transplantation

While extensive evidence indicates that tumor cells shift their global metabolic programs, the molecular details of the metabolic transformation in tumor invasion, progression, and metastasis remain largely unknown. Characterization of the time-dependent metabolic shift during the tumor invasion, development, and metastasis will describe an important aspect of tumor phenotypes and potentially allow us to design therapies that inhibit tumor cell movement. In this study, a metabonomic study was performed to characterize the global metabolic changes during the process of tumor invasion and metastasis to lung in a mouse model with subcutaneous transplantation of murine osteosarcoma cell line (LM8). The serum metabolic profiling revealed that many key metabolites in glycolysis and tricarboxylic acid (TCA) cycle, as well as most of the amino acids were elevated at rapidly growing stage of tumor, presumably resulting from a high energy demand and turnover of anabolic metabolism during the tumor cell proliferation. Serum levels of succinic acid and proline significantly increased (with fold change FC = 10.75 and 4.43, relative to controls) among all the metabolites in the third week. The serum metabolic profile of lung metastasis at week 4 was different from that at week 3, in that most of previously increased serum metabolites were found decreased, except for cholesterol and several free fatty acids, suggesting lowered carbohydrate and amino acids metabolism, but an elevated lipid metabolism associated with tumor metastasis.     

Increased oxidative stress and coenzyme Q10 deficiency in juvenile fibromyalgia: amelioration of hypercholesterolemia and fatigue by ubiquinol-10 supplementation

Abstract

Fibromyalgia (FM) is characterized by generalized pain and chronic fatigue of unknown etiology. To evaluate the role of oxidative stress in this disorder, we measured plasma levels of ubiquinone-10, ubiquinol-10, free cholesterol (FC), cholesterol esters (CE), and free fatty acids (FFA) in patients with juvenile FM (n = 10) and in healthy control subjects (n = 67). Levels of FC and CE were significantly increased in juvenile FM as compared with controls, suggesting the presence of hypercholesterolemia in this disease. However, plasma level of ubiquinol-10 was significantly decreased and the ratio of ubiquinone-10 to total coenzyme Q10 (%CoQ10) was significantly increased in juvenile FM relative to healthy controls, suggesting that FM is associated with coenzyme Q10 deficiency and increased oxidative stress. Moreover, plasma level of FFA was significantly higher and the content of polyunsaturated fatty acids (PUFA) in total FFA was significantly lower in FM than in controls, suggesting increased tissue oxidative damage in juvenile FM. Interestingly, the content of monoenoic acids, such as oleic and palmitoleic acids, was significantly increased in FM relative to controls, probably to compensate for the loss of PUFA. Next, we examined the effect of ubiquinol-10 supplementation (100 mg/day for 12 weeks) in FM patients. This resulted in an increase in coenzyme Q10 levels and a decrease in %CoQ10. No changes were observed in FFA levels or their composition. However, plasma levels of FC and CE significantly decreased and the ratio of FC to CE also significantly decreased, suggesting that ubiquinol-10 supplementation improved cholesterol metabolism. Ubiquinol-10 supplementation also improved chronic fatigue scores as measured by the Chalder Fatigue Scale.     

Increased plasma concentration of 4-pyridone-3-carboxamide-1-ß-D-ribonucleoside (4PYR) in lung cancer. Preliminary studies

Abstract

4-pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR) is a new nicotinamide derivative, which is potentially toxic to the endothelium. Dysfunction of the endothelium promotes cancer cell proliferation, invasiveness, and inflammatory signaling. The aim of this study was to analyze 4PYR concentration in the plasma of lung cancer patients and its relationship to other known biochemical parameters associated with the endothelium function.

The concentration of 4PYR, nicotinamide, 1-methylnicotinamide (MNA), amino acids, and their derivatives were measured in samples obtained from patients with primary squamous cell carcinoma (n?=?48) and control group (n?=?100).

The concentration of 4PYR and 4PYR/MNA ratio were significantly higher in lung cancer patients as compared to controls (0.099?±?0.009 vs. 0.066?±?0.006?µmol/L and 1.10?±?0.08 vs. 1.97?±?0.15, respectively). The plasma arginine/asymmetric dimethylarginine (Arg/ADMA) ratio was considerably lower in lung cancer patients (253?±?17 vs. 369?±?19) as well as plasma MNA (0.057?±?0.004 vs. 0.069?±?0.003?µmol/L). There was no difference in the plasma concentrations of nicotinamide and nicotinamide riboside in both groups (0.116?±?0.019 vs. 0.131?±?0.014 and 0.102?±?0.006 vs. 0.113?±?0.011, respectively).

In this study, a higher 4PYR concentration was observed for the first time in patients with squamous cell carcinoma. This change may be related to the endothelial dysfunction that promote cancer progression since 4PYR and its derivatives are known to disrupt glycolytic pathway.