基于分子影像的非小细胞肺癌分子靶向治疗及免疫治疗进展

我国癌症发病率与死亡率中肺癌均高居第一位，其中非小细胞肺癌（NSCLC）占肺癌85%以上， NSCLC传统治疗方式包括手术、化疗、放疗等。近十几年来，NSCLC相关临床治疗取得巨大突破，代表性治疗新方案即为分子靶向治疗和免疫治疗，然而，上述治疗方式成功发挥治疗作用前提和关键则是精准选择NSCLC患者治疗优势人群。分子影像可以在活体状态下，应用影像学方法对人或动物体内细胞和分子水平生物学过程进行成像、定性和定量研究，着眼于生物过程基础变化而不是生物变化最终结果，进而实现精准选择治疗优势人群、分子水平精准监测治疗效果、及时进行预后评估等目的，对分子靶向治疗以及免疫治疗意义重大。该文综述分子影像在NSCLC分子靶向治疗以及免疫治疗中开展的相关研究。     

ICU和呼吸科患者感染鲍曼不动杆菌危险因素研究

目的 研究患者院内感染鲍曼不动杆菌(Acinetobacter Baumanii,AB)的危险因素。方法 对ICU和呼吸科6 017例患者的临床资料进行回顾性总结和分析,了解其AB院内交叉感染率和危险因素,为院内感控提供理论依据。结果 呼吸科共5 002例,呼吸科感染率是0.59%(30例),ICU共1 015例,ICU感染率是19.70%(200例),差异有统计学意义(P<0.05)。单因素分析,“气道开放”、“广谱抗生素治疗”、“合并基础疾病”是AB感染的危险因素。Logistic回归分析,“气道开放”是独立危险因素。“气道开放”使得两科患者感染率显著增加,但在ICU感染率高于呼吸科,差异有统计学意义(P<0.05)。 有基础疾病与无基础疾病患者感染率,在ICU与呼吸科内比较差异均无统计学意义(P>0.05),但无论是否有基础疾病,在ICU感染率均高于呼吸科,差异有统计学意义,(P<0.05)。同样使用广谱抗生素治疗,在ICU感染率高于呼吸科,差异有统计学意义(P<0.05)。结论 “气道开放”是院内感染AB的关键环节,“广谱抗生素治疗”、“合并基础疾病”是防控鲍曼不动杆菌感染的重要环节,应针对性管理,尤其是ICU。     

Retinoblastoma co-repressor 1 (RB) and cyclin-dependent kinase inhibitor (CDKN) as a multi-gene panel for differentiating pulmonary from non-pulmonary origin in metastatic neuroendocrine carcinomas

BackgroundNeuroendocrine carcinomas (NECs) arise from neuroendocrine cells present throughout the body, and often present with metastases even with small and undetectable primary tumors. Additionally, neuroendocrine differentiation can be seen in carcinomas of non-neuroendocrine origin further complicating the landscape of metastatic NECs. Organ specific immunohistochemical markers such as TTF1, CDX2 and PAX8 are often lost in high grade tumors and may be non-contributory in localizing the primary site.Though NECs share a common cellular origin, they exhibit great variability in biologic behavior, prognosis and treatment based on the primary organ of origin.DesignTwenty one cases of metastatic NECs were retrieved from our archives and were classified based on location of the primary tumor derived from clinical and radiological findings. Next generation sequencing data was retrieved and analyzed for recurrent genetic abnormalities in these cases. Statistical analysis was performed using IBM SPSS25 software.ResultsRB1 mutations were exclusive to NECs metastasizing from lung primary and were detected in 5 of 12 (41.6 %) cases (p = 0.04). CDKN gene family (CDKN1B and 2 A) mutations were limited to metatstatic NECs of non-pulmonary origin and were detected in 4 of 9 (44.4 %) cases (p = 0.02).ConclusionThe location of the primary tumor in metastatic NECs appears to have significant prognostic and therapeutic implications. But due to the morphological homogeneity, higher grade of tumor, variable sensitivity of immunohistochemical markers, and small, often undetectable primary tumors, the localization of the primary tumor in cases of metastatic NECs is a challenge. In this study, RB1 and CDKN gene family mutations are identified as possible markers for differentiating pulmonary and non-pulmonary origin in metatstatic NECs.     

MYC抑制剂与小细胞肺癌关系的研究进展MYC抑制剂与小细胞肺癌关系的研究进展

MYC在多种肿瘤中高表达,发挥重要的生物学作用,MYC抑制剂Omomyc可抑制MYC和其他基因或蛋白结合。Omomyc可停滞小细胞肺癌细胞的细胞周期,并促进细胞凋亡,机制与p21相关。本文综述MYC的概念和作用,总结MYC与肿瘤的关系,论述MYC抑制剂Omomyc的作用机制和研究进展,讨论Omomyc促小细胞肺癌细胞凋亡的作用机制与p21的相关性。MYC与肿瘤密切的关系使MYC抑制剂Omomyc的研究日益重要,本文旨在为临床治疗靶点提供新思路。     

健康信念模式主导的护理干预对空巢老年缺血性脑卒中患者治疗依从性及疗效的影响

目的 探讨健康信念模式教育主导的护理模式在空巢老年脑卒中患者的治疗依从性影响。 方法 选取2011年10月-2015年10月在哈尔滨医科大学附属第四医院神经内科治疗的空巢老年脑卒中患者156例,随机分为研究组78例和对照组78例。对照组实施常规护理,研究组在对照组基础上实施健康信念模式教育主导的护理模式。比较2组治疗后的依从性和满意度;使用简易智能状态检查量表对患者治疗前后的认知功能进行评测,并比较2组生活能力(ADL)及生存质量评分。 结果 研究组患者依从性情况较好,不受症状波动的影响,与对照组比较差异具有统计学意义(P<0.05);研究的护理满意度各个维度的表现明显优于对照组(P<0.05);ADL评分显示,且研究组要优于对照组(P<0.05);治疗后,研究组物质功能评分、心理、社会、日常生活、QOL总分显著低于对照组(P<0.05)。 结论 空巢老年脑卒中患者实施健康信念模式教育主导的护理模式可提高患者满意度、依从性、认知功能及日常生活的能力,使患者的生活质量得到改善。      

Ki-67、TOPⅡα在食管鳞状细胞癌组织中的表达及其与脉管侵犯的相关性

目的:探讨食管鳞状细胞癌组织中Ki-67、TOPⅡα的表达及其与脉管侵犯的相关性。方法:回顾性分析60例食管鳞状细胞癌患者的临床资料,采用免疫组织化学法检测肿瘤组织中Ki-67、TOPⅡα的表达,比较有脉管侵犯者和无脉管侵犯者上述分子标志物表达的差异。结果:46例(76.7％)患者有脉管侵犯,其中在侵犯深度、TNM分期、淋巴结转移及组织学分级方面差异具有统计学意义(P<0.05)。有脉管侵犯者的TOPⅡα、Ki-67的高表达率显著高于无脉管侵犯者(P<0.05)。亚组分析显示,有和无脉管侵犯者之间Ki-67高表达率的差异主要出现于男性、年龄≥65岁、肿瘤最大径＜5 cm、组织学G2-G3级、浸润深度T3及TNM分期Ⅰ-Ⅱ期;有和无脉管侵犯者之间TOPⅡα高表达率的差异主要出现于年龄≥65岁、肿瘤最大径≥5 cm及组织学G2-G3级。Spearman相关性分析显示,Ki-67 和TOPⅡα 两者在食管鳞状细胞癌组织中表达呈正相关（r=0.314,P＝0.015）。结论:有脉管侵犯食管鳞状细胞癌患者的Ki-67、TOPⅡα的阳性表达率显著高于无脉管侵犯者,提示二者在脉管侵犯中起着重要作用。     

Negative Inotropic Action of Alpha-1A Adrenoceptor Blocking Agents: Role of Adenosine and ATP-Sensitive K+ Channels

• 1.The effects of α₁ adrenoceptor blocking agents doxazosin, indoramin, 5-methylurapidil, niguldipine, WB-4101 and chloroethylclonidine (CEC) on the force of contraction (F_c), velocity of contraction (+dF/dt) and relaxation (−dF/dt) of guinea pig papillary muscles were studied.
• 2.All examined substances were applied in a wide concentration range (0.01–30.0 μM) for at least 30 min at each concentration. Only α_1a blockers [i.e., niguldipine (0.01–0.3 μM), 5-methylurapidil (1–30 μM) and WB-4101 (1–30 μM)] showed a concentration-dependent negative inotropic action.
• 3.This effect was significantly attenuated in the presence of glibenclamide (1 μM) and almost completely abolished by 1,3-dipropyl-8-p-sulfophenylxanthine (1 μM), an antagonist of adenosine receptors with a slight selectivity for the A₁ subtype.
• 4.Pretreatment with dibenamine, an irreversible blocker of α₁ adrenoceptors (0.6 μM for 40 min), abolished this effect, whereas pretreatment with CEC, an irreversible blocker of α_1b adrenoceptors (1 μM for 20 min), and pertussis toxin (10 μg/kg IP, 4 to 5 days before experiments) diminished it.
• 5.The α_1a adrenoceptor blocking agents in the presence of the unblocked α_1b adrenoceptor trigger the negative inotropic action, which seems to include adenosine receptor stimulation and activation of ATP-sensitive K⁺ channels (K_ATP) through an inhibitory G protein.

     

Reliability and significance of DNA measurements in interphase nuclei and division figures in histological sections

DNA contents from single cells at interphase and division were analysed in histological sections and in imprints from 73 breast cancer specimens. Fetal livers from 18 terminations of normal pregnancies provided the standard for truly mitotic prophases, metaphases and telophases. The reliability of DNA quantities from image microphotometry was improved using paraffin-embedded tissue samples from which 4, 8 and 15 μm slices were Feulgen stained. Imprinted replicas from the mirror surface of each freshly cut specimen provided matching domains and represent the crucial approach in this project. A close positive relationship was observed between interphase nuclei in 8 μm sections and their imprinted counterparts (r=0.992; n=73). Interphase nuclei in 4 μm sections yielded insufficient DNA contents when compared with the imprints (r=0.815; n=21) and with endogenous lymphocyte nuclei. This 2 c DNA standard also calibrated 232 mitotic figures to 3.91±0.01 c in 15 μm sections from fetal liver. Prophases, metaphases and telophases were slightly scattered (coefficient of variation=0.04 each). The 0.09 c deficiency to plain 4.0 c was read as an artifact from sectioning. However, the methodical bias did not challenge the most irregular DNA distribution profiles recorded from chromosome division figures (CDFs) in 15 μm sections of breast cancers. Poorly differentiated and aggressive breast cancer (Auer type IV, Zetterberg type A) exhibited a 4.5 c exceeding rate of 82.24% from a total of 752 CDFs in 10 randomly selected cases. Well differentiated, slowly growing cancer with diploid interphase nuclei (Auer I, Zetterberg D) surprisingly showed a 4.5 c exceeding rate of 29.26% from a total of 173 mitoses and CDFs in 10 randomly selected cases. The bulk of data beyond the mitotic 4.0 c level discriminates biological bias from methodical impairment. We concluded that 8 μm sections are sufficient for human interphase nuclei, whereas a depth of 15 μm preserves intact mitoses and CDFs.