Tumor microenvironment characterization identifies two lung adenocarcinoma subtypes with specific immune and metabolic state

The tumor microenvironment (TME) is a vital component of tumor tissue. Increasing evidence suggests their significance in predicting outcomes and guiding therapies. However, no studies have reported a systematic analysis of the clinicopathologic significance of TME in lung adenocarcinoma (LUAD). Here, we inferred tumor stromal cells in 1184 LUAD patients using computational algorithms based on bulk tumor expression data, and evaluated the clinicopathologic significance of stromal cells. We found LUAD patients showed heterogeneous abundance in stromal cells. Infiltration of stromal cells was influenced by clinicopathologic features, such as age, gender, smoking, and TNM stage. By clustering stromal cells, we identified 2 clinically and molecularly distinct LUAD subtypes with immune active and immune repressed features. The immune active subtype is characterized by repressed metabolism and repressed proliferation of tumor cells, while the immune repressed subtype is characterized by active metabolism and active proliferation of tumor cells. Differentially expressed gene analysis of the two LUAD subtypes identified an immune activation signature. To diagnose TME subtypes practically, we constructed a TME score using principal component analysis based on the immune activation signature. The TME score predicted TME subtypes effectively in 3 independent datasets with areas under the receiver operating characteristic curves of 0.960, 0.812, and 0.819, respectively. In conclusion, we proposed 2 clinically and molecularly distinct LUAD subtypes based on tumor microenvironment that could be valuable in predicting clinical outcome and guiding immunotherapy.     

镍铬烤瓷合金修复体中金属元素含量无损检测方法的研究

目的探讨镍铬烤瓷合金修复体中Co、Pb、Cd、Ti、Mn、As、Hg含量无损检测的方法。方法参照镍铬烤瓷合金厂家标记的主要元素含量和有损检测精确测定的结果,采用熔融制样法制作无损检测的标准样品,选用X射线荧光光谱法(XRF)无损检测技术测定镍铬烤瓷合金样品中的Co、Pb、Cd、Ti、Mn、As、Hg的含量。结果镍铬烤瓷合金样品中的As和Hg的含量未能通过无损检测方法检出,但XRF测定Co、Pb、Cd、Ti、Mn的结果与有损检测法测定结果十分接近。结论X射线荧光光谱法作为镍铬烤瓷合金修复体中金属元素含量的一种无损检测方法,具有检测结果可靠、精度较高、测定速度较快、不损坏样品的优点,在选定的实验条件下,相对标准偏差在0.21%~4.20%。     

Aberrant oligodendroglial LDL receptor orchestrates demyelination in chronic cerebral ischemia

Oligodendrocytes express low-density lipoprotein receptor (LDLR) to endocytose cholesterol for the maintenance of adulthood myelination. However, the potential role of LDLR in chronic cerebral ischemia–related demyelination remains unclear. We used bilateral carotid artery stenosis (BCAS) to induce sustained cerebral ischemia in mice. This hypoxic-ischemic injury caused a remarkable decrease in oligodendroglial LDLR, with impaired oligodendroglial differentiation and survival. Oligodendroglial cholesterol levels, however, remained unchanged. Mouse miR-344e-3p and the human homolog miR-410-3p, 2 miRNAs directly targeting Ldlr, were identified in experimental and clinical leukoaraiosis and were thus implicated in the LDLR reduction. Lentiviral delivery of LDLR ameliorated demyelination following chronic cerebral ischemia. By contrast, Ldlr^–/– mice displayed inadequate myelination in the corpus callosum. Ldlr^–/– oligodendrocyte progenitor cells (OPCs) exhibited reduced ability to differentiate and myelinate axons in vitro. Transplantation with Ldlr^–/– OPCs could not rescue the BCAS-induced demyelination. Such LDLR-dependent myelin restoration might involve a physical interaction of the Asn-Pro-Val-Tyr (NPVY) motif with the phosphotyrosine binding domain of Shc, which subsequently activated the MEK/ERK pathway. Together, our findings demonstrate that the aberrant oligodendroglial LDLR in chronic cerebral ischemia impairs myelination through intracellular signal transduction. Preservation of oligodendroglial LDLR may provide a promising approach to treat ischemic demyelination.     

度洛西汀与氟西汀治疗躯体形式障碍对照研究

目的：探讨度洛西汀与氟西汀治疗躯体形式障碍的临床疗效和安全性。方法将80例躯体形式障碍患者随机分为两组,研究组口服度洛西汀治疗,对照组口服氟西汀治疗,观察6周。于治疗前后采用临床疗效大体评定量表、症状自评量表的躯体化、焦虑、抑郁因子评定临床疗效,副反应量表评定不良反应。结果治疗6周末,研究组显效率69．2％、总有效率89．7％,对照组分别为44．4％、75．0％,研究组显效率显著高于对照组（χ2＝4．70,P＜0．05）,总有效率高于对照组,但差异无显著性（χ2＝2．84,P＞0．05）。治疗各时段副反应量表评分均显著低于对照组（P＜0．01）。结论度洛西汀与氟西汀治疗躯体形式障碍疗效均显著,但度洛西汀治疗起效更快、疗效更显著、安全性更高、依从性更好。     

10例原发性气管肿瘤的外科诊断及手术治疗

目的总结外科手术治疗原发性气管肿瘤的临床经验。方法回顾分析本院1993年10月～2010年1月收治的10例气管肿瘤的诊断和治疗经验。结果本组鳞癌3例,腺癌3例,腺鳞癌1例,良性肿瘤3例;临床治愈9例,术后3d死亡1例。本组3例鳞癌患者分别于手术后3年和8个月复发死亡;3例腺癌,1例术后1年出现肺转移,另2例存活10个月。结论手术切除是治疗气管肿瘤最有效的方法：（1）纤维支气管镜检查与多排CT增强三维成像对确定气管肿瘤范围有互补作用;（2）充分的术前呼吸道准备,是术中安全、术后顺利康复的保障;（3）手术者和麻醉医师密切配合,选择视野较宽的纤维支气管镜引导气管插管是麻醉安全的重要保障。     

刘云山主任医师治疗小儿发热经验之信息化研究

目的 基于中医传承辅助平台（V2．0）软件,分析刘云山主任医师治疗小儿发热用药经验。方法收集刘云山主任医师治疗小儿发热的病案,录入“中医传承辅助平台”,采用该软件集成的规则分析、改进互信息法等数据挖掘方法,分析刘云山主任医师治疗小儿发热用药经验。结果对筛选出的100个处方进行分析,确定处方中各种药物的使用频次,药物之间的关联规则。结论刘云山主任医师治疗小儿发热特点为疗热驱邪外,善施和解法。发热之治,或辛散透表,或清里攻下,或表里双解,关键在给邪出路。对半表半里证,要明确诊断,随寒热虚实而治,或佐疏利透达,或佐清热导下,或佐调和肝脾,随证施法,依法选方。中医传承辅助系统可用于名老中医临床经验分析与总结。     

糖化酶超滤速度的研究

以浓差极化-凝胶层数学模型为基础,研究了影响糖化酶超滤速度的各种因素。结果表明:在浓差极化现象存在下,超滤速度随透出液体积和主体溶液浓度的增大而减小,随搅拌速度或料液流速的增大而增大。提高操作压力不会增大超滤速度。对糖化酶发酵液进行絮凝处理及适当提高温度都有利于超滤速度的提高。     

TACE联合RF和TACE治疗中晚期肝癌的临床观察

目的　探讨中晚期肝癌 (hepatocellularcarcinoma ,HCC)经皮穿刺肝动脉化疗栓塞 (tran shepaticarterychemoembolization ,TACE)联合集束电极射频 (radiofrequency ,RF)的治疗效果。 方法　 3 2例HCC病人在TACE 2～ 3周后行RF治疗 (联合组 )与同期经二次TACE的 3 4例 (TACE组 )比较。结果　联合组在瘤体缩小 (P <0 0 1)、AFP下降、自觉症状改善等方面好于TACE组 ,且骨髓抑制少 (P <0 0 5 ) ,肝功能损害轻 (P <0 0 1)。结论　TACE联合RF治疗中晚期肝癌 ,具有相互加强作用 ,是一种有效的联合治疗方法     

细胞外信号调节激酶在NGF/VEGF介导的神经保护作用中的动态变化及其调控机制

目的探讨细胞外信号调节激酶1(ERK1)在局灶性脑缺血/再灌注不同时间、不同脑区的动态时空变化,以及其在NGF/VEGF介导的神经保护作用中的调控表达机制。方法采用兔大脑中动脉阻断(MCAO)局灶性脑缺血再灌注模型,所有动物随机分为假手术组(n=6)、缺血/再灌注组(n=60)、因子干预组(n=40)。应用免疫组化检测ERK1在脑缺血/再灌注损伤不同脑区的动态表达,同时,应用免疫组化、流式细胞术和电镜检测caspase-3表达、凋亡和超微结构的变化。结果免疫组化分析显示,再灌注损伤1hERK1首先在海马CA3和齿状回(DG)表达增加,6h后其它脑区也相继增加,随再灌注时间延长而加剧,1~3d达高峰。再灌注1hcaspase-3活性表达在各脑区迅速增加,3d达高峰。应用神经保护剂(NGF/VEGF)后各脑区ERK1表达呈明显抑制,caspase-3表达同时被抑制。结论ERK信号通路可能通过调节死亡受体途径介导神经保护作用,抑制ERK信号途径可能是减轻脑缺血损伤过程中神经细胞死亡的有效方法。     

高压氧辅助治疗突发性聋的疗效观察

目的观察高压氧辅助治疗对于突发性聋治疗效果的影响。方法100例按入院时间先后随机分为高压氧治疗组50例（55耳）和对照组50例（53耳）。治疗前后判断疗效分布。结果高压氧治疗组总有效率89．2％，对照组有效率70％。两组患者治疗后疗效比较差异有显著性意义（P〈0．05）。结论高压氧辅助治疗突发性聋比单纯药物治疗治愈率高，临床可首选。