Serum tissue polypeptide-specific antigen is an independent predictor in breast cancer

Tissue polypeptide-specific antigen (TPS) is a tumor proliferative marker associated with cytokeratin 18. The aim of the study was to investigate the potential relationship between the preoperative serum TPS levels and the outcome in Chinese breast cancer patients. 975 consecutive female patients, affected by invasive breast cancer under investigation from January 2005 to December 2011, had their TPS levels measured with a one-step solid phase radiometric sandwich assay detecting the M3 epitope on cytokeratin 18 fragments. The cut-off value was 80 U/L. The average age diagnosed with breast cancer was 48, ranging from 23 to 71. About 19% (185) patients displayed an elevated preoperative TPS level (>80 U/L) associated with older age (>45), advanced cancer stage, larger tumor size (>2 cm), axillary lymph node metastasis, negative progesterone receptor status, and positive HER2 status. In addition, preoperative TPS levels were also significantly connected with recurrence (p < 0.05), particularly distant metastasis and visceral metastasis. The mean preoperative TPS level was 68.4 ± 116.43 U/L (range 0–1839 U/L). In multivariate analysis, high preoperative TPS level was recognized as an independent prognostic factor for disease-free survival (p < 0.001 and overall survival (p = 0.023). From these results we conclude that the serum preoperative TPS level may be a valuable and independent marker for breast cancer.     

Cell death and autophagy in tuberculosis

Mycobacterium tuberculosis has succeeded in infecting one-third of the human race though inhibition or evasion of innate and adaptive immunity. The pathogen is a facultative intracellular parasite that uses the niche provided by mononuclear phagocytes for its advantage. Complex interactions determine whether the bacillus will or will not be delivered to acidified lysosomes, whether the host phagocyte will survive infection or die, and whether the timing and mode of cell death works to the advantage of the host or the pathogen. Here we discuss cell death and autophagy in TB. These fundamental processes of cell biology feature in all aspects of TB pathogenesis and may be exploited to the treatment or prevention of TB disease.     

心脑血管病危险因素与颈动脉粥样硬化的相关性

目的 探讨心脑血管病危险因素与颈动脉粥样硬化的相关性。方法 选择2010年8月～2013年8月健康体检者916例,依据合并危险因素的数量将受试者分为4组,即0个危险因素组（对照组）226例,1个危险因素组239例,2个危险因素组234例,≥3个危险因素组217例。所有受试者均进行颈动脉超声检测及血生化检测。结果 对照组患者斑块发生率为7.52%,1个危险因素组为15.06%,2个危险因素组为23.93%,≥3个危险因素组为45.16%,从对照组到合并≥3个危险因素组斑块发生率显著上升（P<0.01）。4组受试者IMT分别为0.94±0.32 mm、1.12±0.34 mm、1.25±0.33 mm及1.37±0.39 mm,斑块Crouse积分分别为0.24±0.64、0.58±1.21、0.85±1.26及1.32±1.64。从对照组到合并≥3个危险因素组IMT及斑块Crouse积分逐渐增高（P<0.01）。Logistic回归分析显示,1个危险因素组颈动脉粥样硬化斑块发生率为对照组的1.27倍,2个危险因素组为2.31倍,≥3个危险因素组为4.68倍（P<0.01）。结论 危险因素之间对缺血性脑血管病高危人群颈动脉粥样硬化及斑块的发生具有显著的联合协同作用。     

重组人肿瘤坏死因子相关弱凋亡诱导因子对小鼠主动脉内皮舒张功能及凝血相关因子的影响

目的 采用重组人肿瘤坏死因子相关弱凋亡诱导因子（rhTWEAK）经腹腔注射,诱导血管内皮损伤模型,观察rhTWEAK对小鼠主动脉内皮舒张功能和凝血相关因子的影响。方法 3～4周龄C57BL小鼠32只,随机分成4组,每组8只,腹腔注射各药物：①rhTWEAK组：rhTWEAK按5 μg/（kg·d）的量溶于生理盐水,共0.3 mL,腹腔注射,连续注射7天;②rhTWEAK＋抗rhTWEAK组：先给予抗rhTWEAK腹腔注射,15 min后再给予rhTWEAK注射;③IgG组：给予小鼠非特异性IgG腹腔注射;④对照组：给予0.3 mL生理盐水注射。分别在干预1周后眼球取血,分离上清;取小鼠胸主动脉段进行血管舒张功能的检测。酶联免疫吸附法检测血浆中内皮型一氧化氮合酶（eNOS）、高敏C反应蛋白（hs-CRP）、一氧化氮（NO）、组织因子（TF）、组织因子途径抑制物（TFPI）含量。结果 ①与对照组、rhTWEAK＋抗rhTWEAK组、IgG组相比,rhTWEAK组内皮依赖性血管舒张功能、血浆中eNOS、NO、TFPI水平明显降低,TF水平明显升高,均有统计学意义（均P<0.05）;血浆中hs-CRP含量未见明显改变（P>0.05）;②rhTWEAK组、IgG组与对照组相比,血管内皮舒张功能、血浆中NO、TF、TFPI、eNOS、hs-CRP含量变化均无统计学差异（均P>0.05）。结论 rhTWEAK可诱导内皮功能紊乱和凝血相关因子含量的改变,这可能是TWEAK参与动脉粥样硬化早期血管内皮损害的机制。     

p38MAPK介导PDGF-BB诱导的大鼠血管平滑肌细胞MMP-2基因表达

目的　观察血小板源性生长因子BB（PDGF-BB）是否可以诱导大鼠血管平滑肌细胞（VSMC）基质金属蛋白酶2（MMP-2）基因表达及VSMC的迁移,探讨p38信号通路在这一过程中的作用,为血管重建性疾病的研究提供实验依据。方法　PDGF-BB不同浓度和不同时间刺激体外培养的大鼠VSMC,用放线菌素D、SB202190（MAPK/p38特异性抑制剂）处理PDGF-BB诱导的VSMC。细胞划痕实验检测细胞迁移,运用Real-time　RT-PCR检测MMP-2基因表达水平,Western　blot　检测p38的活性变化。结果　PDGF-BB可促进VSMC迁移,SB202190可抑制PDGF-BB诱导的VSMC迁移。不同浓度PDGF-BB（10　μg/L～50　μg/L）作用VSMC　0.5　h,MMP-2基因表达明显增加,其中以20　μg/L较显著;用20　μg/L　PDGF-BB作用VSMC　0.5　h～4　h,可显著上调MMP-2基因表达,以0.5　h较显著。用放线菌素D和SB202190预处理后MMP-2基因表达降低。PDGF-BB可激活VSMC中磷酸化p38水平,SB202190可抑制　p38的磷酸化以及相应的MMP-2基因表达。结论　p38参与了PDGF-BB诱导的VSMC迁移及MMP-2基因表达。     

中晚期慢性肾脏病患者成纤维细胞生长因子23水平与颈动脉粥样硬化的关系

目的　探讨中晚期慢性肾脏病（CKD）患者成纤维细胞生长因子23（FGF23）水平与颈动脉粥样硬化的相关性。方法　收集我院中晚期慢性肾脏病患者共计120例,分为3组,其中CKD非透析组患者（3～5期）30例、腹膜透析组患者30例、血液透析组患者60例;另外选择年龄、性别匹配的20例健康体检者为健康对照组。比较中晚期慢性肾脏病患者与健康人群FGF23水平的差别,以及3组之间的差别。同时将中晚期CKD患者分为颈动脉粥样硬化组和无颈动脉粥样硬化组,比较两组临床有关参数及FGF23水平的变化,探讨FGF23水平与颈动脉粥样硬化的相关性,分析其临床意义。结果　中晚期CKD患者颈动脉粥样硬化发生率较高（59/120,49.2%）。颈动脉粥样硬化组血清FGF23水平明显高于无颈动脉粥样硬化组（P<0.01）;中晚期CKD患者血清FGF23水平显著高于健康对照组（P<0.01）;中晚期CKD患者3组人群比较,透析患者FGF23水平高于非透析的CKD　3～5期患者（P<0.05）;血液透析患者的FGF23水平又显著高于腹膜透析患者（P<0.01）。中晚期CKD患者FGF23水平与颈动脉内膜中层厚度呈正相关（r＝0.68,P<0.05）,多因素分析显示,FGF23水平是中晚期慢性肾脏病患者发生颈动脉粥样硬化的独立危险因素。结论　血清FGF23水平与中晚期CKD患者颈动脉粥样硬化的发生相关,FGF23在颈动脉粥样硬化的发生发展中可能起着重要作用。FGF23可能成为预测CKD患者发生心血管疾病和死亡风险性增高的更敏感的标志物之一。     

Active tuberculosis in inflammatory bowel disease patients under treatment from an endemic area in Latin America

BACKGROUNDThere has been an increase in cases of inflammatory bowel disease (IBD) in recent years. There is also greater access and availability of immunosuppressive and biological agents, which increase the risk of opportunistic infection despite improving the quality of life and promoting mucosal healing. Tuberculosis (TB) remains a public health problem, and it has a high incidence in several countries. Therefore, knowledge of the risk of developing TB in patients with IBD is important.AIMTo evaluate the risk of active TB in patients with IBD under treatment from an endemic area in Latin America.METHODSA standard questionnaire included demographic variables, clinical aspects of IBD disease, history of active TB during treatment, active TB characteristics and evolution, initial screening and results and time from the start of anti-tumor necrosis factor alpha (TNFα) to TB development.RESULTSAzathioprine, anti-TNFα and the combination of these two drugs were associated with a higher risk of active TB incidence. The TNFα blockers increased the relative risk of developing active TB compared to other treatments. All four multivariable models showed that the use of TNFα blockers alone or in combination with azathioprine was an important risk factor for the incidence of active TB. After adjustment for sex, age, type of IBD and latent TB, anti-TNFα with azathioprine increased the relative risk to 17.8 times more than conventional treatment. Late TB, which was diagnosed 3 mo after the start of anti-TNFα, was the most frequent.CONCLUSIONTreatment with anti-TNFα increased the risk of active TB in IBD patients from an endemic area in Latin America. This risk was increased when anti-TNFα was combined with azathioprine. The time from the beginning of the treatment to the active TB diagnosis suggests a new TB infection.     

肿瘤坏死因子-α拮抗剂对类风湿关节炎和强直性脊柱炎患者血清白细胞介素-17和外周血 Th17细胞比例的影响

目的初步探讨外周血 Th17细胞亚群的比例以及 IL-17的表达水平在 RA 和 AS 患者接受 TNF-α拮抗剂治疗前后的改变及其意义。方法选择 RA 患者27例和 AS 患者22例,2种疾病中各有14例患者接受 TNF-α拮抗剂治疗40周。对照组24名来源于健康献血者。采用流式细胞术检测外周血 CD4+T 细胞中 Th17细胞亚群的比例,ELISA 检测外周血 IL-17表达水平。符合正态分布数据采用2个独立样本 t 检验,不符合正态分布则采用 Wilcoxon 秩和检验,患者治疗前后的比较采用配对 t 检验。结果治疗前,RA 和 AS 患者外周血 CD4+ T 细胞中 Th17细胞亚群的比例显著高于健康对照组[RA 1.03%（0.66%,1.78%）与健康对照0.50%（0.43%,0.67%）,Z=-3.236,P<0.01;AS（1.16±0.09）%与健康对照（0.59±0.06）%,t=5.226,P<0.01]。同样,IL-17的表达水平在2组疾病中也显著升高[RA（32.3±2.5） pg/ml,健康对照（14.3±2.5） pg/ml,t=5.070,P<0.01;AS 28.98（23.84,36.14） pg/ml,健康对照11.84（5.33,22.12） pg/ml,Z=-4.103,P<0.01]。 TNF-α拮抗剂治疗后,2组疾病 CD4+T 细胞中 Th17细胞亚群比例无明显变化[RA 驻（0.1045±0.2126）%;AS 驻（0.0025±0.1838）%],但 IL-17表达水平则明显下降[RA 驻（-13.5±5.0） pg/ml;AS 驻（-16.0±1.9） pg/ml]。结论 Th17细胞及其分泌的细胞因子 IL-17在 RA 和 AS 的发病机制中起重要作用,TNF-α拮抗剂对 AS 和 RA 患者 Th17细胞亚群炎症细胞因子的分泌功能有明显的抑制作用,但40周的治疗仍不能降低 Th17细胞比例,这可能是 TNF-α拮抗剂短期治疗后疾病复发的原因之一。     

Inflammatory bowel disease: An increased risk factor for neurologic complications

Only a very few systematic studies have investigated the frequency of neurologic disorders in patients with Crohn’s disease(CD) and ulcerative colitis(UC), which are the two main types of inflammatory bowel disease(IBD). Results have been inconsistent and variable, owing to differences in case-finding methods and evaluated outcomes in different studies. The most frequent neurologic manifestations reported in CD and UC populations are cerebrovascular disease(with either arterial or venous events), demyelinating central nervous system disease, and peripheral neuropathy(whether axonal or demyelinating); however, the literature describes numerous nervous system disorders as being associated with IBD. The pathogenesis of nervous system tissue involvement in IBD has yet to be elucidated, although it seems to be related to immune mechanisms or prothrombotic states. The recently-introduced tumor necrosis factor(TNF) inhibitors have proven successful in controlling moderate to severe IBD activity. However, severe neurologic disorders associated with TNF inhibitors have been reported, which therefore raises concerns regarding the effect of anti-TNF-α antibodies on the nervous system. Although neurological involvement associated with IBD is rarely reported, gastroenterologists should be aware of the neurologic manifestations of IBD in order to provide early treatment, which is crucial for preventing major neurologic morbidity.