BACKGROUND & AIMS: :Many aspects of ventilatory management in patients with ARDS are still controversial and one of the major controversies is should HFO or CMV ideally be used to manage this patients. As shown by David et al. when the two approaches to ventilatory support are applied using similar principles the physiologic outcomes appear to be similar. With both approaches the use of lung recruitment maneuvers early in ARDS (1 to 3 day) after hemodynamic stabilization in patients without baratrauma is promising. The key to managing ARDS regardless of mode is to use an open lung protective ventilatory strategy. It is not the mode that makes the difference, it is the approach used to apply the mode!

背景与目标： : ARDS患者通气管理的许多方面仍然存在争议，主要争议之一是是否应理想地使用HFO或CMV来管理该患者。如David等人所示。当使用相似的原理应用两种通气支持方法时，生理结果似乎是相似的。对于两种方法，在没有baratrauma的患者中，在血流动力学稳定后的ARDS早期 (1至3天) 使用肺募集动作是有希望的。无论哪种模式，管理ARDS的关键是使用开放的肺保护性通气策略。与众不同的不是模式，而是用于应用模式的方法!

BACKGROUND & AIMS: Inflammatory cell infiltration of the lung is a predominant histopathological change that occurs during radiation pneumonitis. Emigration of inflammatory cells from the circulation requires the interaction between cell adhesion molecules on the vascular endothelium and molecules on the surface of leukocytes. We studied the immunohistochemical pattern of expression of cell adhesion molecules in lungs from mice treated with thoracic irradiation. After X-irradiation, the endothelial leukocyte adhesion molecule 1 (ELAM-1; E-selectin) was primarily expressed in the pulmonary endothelium of larger vessels and minimally in the microvascular endothelium. Conversely, the intercellular adhesion molecule 1 (ICAM-1; CD54) was expressed in the pulmonary capillary endothelium and minimally in the endothelium of larger vessels. Radiation-mediated E-selectin expression was first observed at 6 h, whereas ICAM-1 expression initially increased at 24 h after irradiation. ICAM-1 and E-selectin expression persisted for several days. P-selectin is constitutively expressed in Weibel-Palade bodies in the endothelium, which moved to the vascular lumen within 30 min after irradiation. P-selectin was not detected in the pulmonary endothelium at 6 h after irradiation. The radiation dose required for increased cell adhesion molecule expression within the pulmonary vascular endothelium was 2 Gy, and expression increased in a dose-dependent manner. These data demonstrate that ICAM-1 and E-selectin expression is increased in the pulmonary endothelium following thoracic irradiation. The pattern of expression of E-selectin, P-selectin, and ICAM-1 is distinct from one another.

背景与目标： 肺炎性细胞浸润是放射性肺炎期间发生的主要组织病理学变化。炎症细胞从循环中迁移需要血管内皮上的细胞粘附分子与白细胞表面的分子之间的相互作用。我们研究了经胸部照射治疗的小鼠肺中细胞粘附分子表达的免疫组织化学模式。X射线照射后，内皮白细胞粘附分子1 (ELAM-1; E-选择素) 主要在较大血管的肺内皮中表达，而在微血管内皮中表达最少。相反，细胞间粘附分子1 (ICAM-1; CD54) 在肺毛细血管内皮中表达，而在较大血管的内皮中表达最少。首先在6小时观察到辐射介导的E-选择素表达，而ICAM-1表达最初在辐射后24小时增加。ICAM-1和E-选择素表达持续数天。P-选择素在内皮的Weibel-Palade体中组成性表达，在照射后30分钟内移至血管腔。照射后6小时，在肺内皮中未检测到P-选择素。肺血管内皮细胞粘附分子表达增加所需的辐射剂量为2 Gy，并且表达以剂量依赖性方式增加。这些数据表明，胸部照射后，肺内皮中ICAM-1和E-选择素的表达增加。E-选择素，P-选择素和ICAM-1的表达模式彼此不同。

BACKGROUND & AIMS: :A diagnosis of low-grade fibromyxoid sarcoma (LGFMS) remains problematic because of its bland-looking histologic features that can be potentially confused with other benign or low-grade fibromyxoid lesions. Recent cytogenetic and molecular analyses have shown that most LGFMSs have a characteristic chromosomal abnormality, t(7;16)(q33;p11), resulting in the FUS-CREB3L2 fusion gene. However, such assays have only rarely been used to analyze formalin-fixed, paraffin-embedded tumor samples. In the present study, we conducted a reverse transcription-polymerase chain reaction assay to detect the FUS-CREB3L2 fusion transcripts using formalin-fixed, paraffin-embedded tumor tissue specimens from 16 LGFMSs including 3 cases with giant collagen rosettes. The primers were newly designed to specifically amplify most of the junctional regions of the FUS-CREB3L2 fusion gene transcripts previously reported. The FUS-CREB3L2 fusion gene transcripts were detected in 14/16 (88%) cases of LGFMS. A nucleotide sequence analysis of the PCR products revealed that different portions of the FUS exon 6 or 7 were fused with various sites of the CREB3L2 exon 5, resulting in 12 different nucleotide sequences. We also tested a primer set to detect the FUS-CREB3L1 fusion transcript, which is a rare variant of the gene fusion in LGFMS, although no PCR products were identified in any case. The FUS-CREB3L2 fusion transcripts were not detected in any of the 123 other soft-tissue tumors, including desmoid-type fibromatoses, myxofibrosarcomas, soft-tissue perineuriomas, and congenital or adult fibrosarcomas. These data suggest that our reverse transcription-polymerase chain reaction assay is a reliable method to detect FUS-CREB3L2, which can thus help in accurately diagnosing LGFMS.

背景与目标： : 低度纤维粘液样肉瘤 (LGFMS) 的诊断仍然存在问题，因为其外观平淡无奇的组织学特征可能与其他良性或低度纤维粘液样病变相混淆。最近的细胞遗传学和分子分析表明，大多数lgfms具有特征性的染色体异常t(7;16)(q33;p11)，导致FUS-CREB3L2融合基因。然而，这种测定很少用于分析福尔马林固定的石蜡包埋的肿瘤样品。在本研究中，我们进行了逆转录聚合酶链反应分析，以使用来自16个lgfms的福尔马林固定，石蜡包埋的肿瘤组织标本 (包括3例巨大的胶原玫瑰花结) 检测FUS-CREB3L2融合转录本。新设计了引物，以特异性扩增先前报道的FUS-CREB3L2融合基因转录物的大部分连接区域。在14/16 (88%) 例LGFMS中检测到FUS-CREB3L2融合基因转录本。PCR产物的核苷酸序列分析表明，FUS外显子6或7的不同部分与CREB3L2外显子5的不同位点融合，产生12种不同的核苷酸序列。我们还测试了引物集以检测FUS-CREB3L1融合转录本，这是LGFMS中基因融合的罕见变体，尽管在任何情况下均未鉴定出PCR产物。在123种其他软组织肿瘤中均未检测到FUS-CREB3L2的融合转录物，包括纤维瘤型纤维瘤，粘液纤维肉瘤，软组织神经瘤和先天性或成人纤维肉瘤。这些数据表明，我们的逆转录-聚合酶链反应测定法是检测FUS-CREB3L2的可靠方法，因此可以帮助准确诊断LGFMS。

BACKGROUND & AIMS: OBJECTIVE:The purpose of our study was to evaluate the effects of 0.3-second high-resolution CT (HRCT) of the lung using partial reconstruction on cardiac motion artifacts and image noise. SUBJECTS AND METHODS:Thirty-seven pairs of 0.3-second (partial reconstruction) and 0.75-second (full reconstruction) HRCT images were obtained for the lower lung zone during full-inspiration breath-holding. Imaging parameters other than temporal resolution were identical for each patient. Two radiologists visually graded motion artifacts of the cardiac border, bronchi, pulmonary vessels, and fissure in the left lung on a 4-point scale (with 4 indicating no artifacts). The maximum width of motion along the left cardiac border and the area percentage of motion artifacts in the left lung were calculated. Image noise in the air and lung was also determined. Cardiac motion artifacts and image noises were compared between the two sets of CT images. RESULTS:Visual grades for the cardiac border (4 +/- 0), bronchi (3.8 +/- 0.7), pulmonary vessels (3.6 +/- 0.8), and fissure (3.9 +/- 0.5) were higher for 0.3-second images than for 0.75-second images (1.7 +/- 0.7, 2.0 +/- 1.0, 1.6 +/- 0.7, and 2.4 +/- 0.9, respectively) (p < 0.001). The maximum width of motion along the left cardiac border (0.1 +/- 0.5 mm) and the area percentage of motion artifacts in the left lung (6.7% +/- 18.4%) were smaller for 0.3-second images than for 0.75-second images (4.5 +/- 1.7 mm and 36.2% +/- 20.9%, respectively) (p < 0.001). Image noises in the air (38.0 +/- 9.2) and the lung (86.0 +/- 23.1) were greater for 0.3-second images than for 0.75-second images (35.6 +/- 9.6 and 76.0 +/- 20.3, respectively) (p < 0.01). CONCLUSION:Compared with 0.75-second HRCT using full reconstruction, 0.3-second HRCT using partial reconstruction substantially reduces cardiac motion artifacts in the lung at the expense of increasing image noise.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:To investigate renal preservation by a novel method of perfusion using an oxygenated perfluorocarbon (PFC) emulsion via retrograde access to the kidney, as preserving renal function during urological surgery has been elusive, and the recognized technique of nephron-sparing surgery has increased its application and practice in modern urology. MATERIALS AND METHODS:After institutional review and approval, 30 New Zealand White rabbits were studied. In a solitary kidney model, each rabbit had the ureter catheterized before 40 min of renal artery occlusion. Each rabbit was randomized to one retrograde perfusion group, i.e. sham, normothermic PFC, chilled PFC, normothermic saline, and chilled saline. The rabbits were maintained for 2 weeks, during which renal function, urine output, systemic blood gases, weight and serum creatinine level were measured. After death, the kidneys were individually examined and graded by one renal pathologist unaware of the treatment. RESULTS:The rabbits treated with retrograde PFC perfusion (normothermic and chilled) had less change in their creatinine clearance, at 3.6 and 4.0 mL/min per kg, than the sham group, at 7.8 mL/min per kg, while also having significantly higher systemic venous oxygenation, at 26.3 and 10.0 mmHg, than the sham group, at 0.2 mmHg. Normothermic and chilled perfusion with PFC was also associated with less histological evidence of ischaemic damage, with mean (sd) scores of 13.0 (13.5) and 8.7 (4.5), respectively, than in the sham group, at 33.3 (16.8), while favourably matching the contralateral control kidney group, at 5.5 (2.3). The rabbits treated with saline retrograde perfusion also had better outcomes than the sham cohort. There were no adverse effects in any of the study arms or with the use of PFC. CONCLUSION:Retrograde oxygen delivery to the kidney through the urinary collecting system was successful in this pilot study. Renal function, laboratory and histological data indicate a trend towards renal preservation and even systemic oxygenation in the experimental groups compared with the sham rabbits, with no adverse effects attributed to this technique.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Side-stream spirometry offers a non-invasive method to monitor continuously respiratory mechanics in intubated patients. We studied the effects of different positions on dynamic lung compliance during anaesthesia. METHODS:The study consisted of 56 patients, operated in supine, prone, kneeling or lateral park-bench position. Dynamic lung compliance and inspiratory peak pressure were recorded after induction of anaesthesia, 15 min and 1 h after posturing the patient. RESULTS:The first measured compliances were comparable in all groups. The compliance in the lateral and the prone positions was significantly lower than in the supine position at 15 min (P < 0.01) and 1 h (P < 0.001) after the posture change. The peak inspiratory pressure was significantly lower in the kneeling position than in the other groups (P < 0.01 at the first measurement, P < 0.001 at the later measurements). No correlation was found between body mass index and compliance. CONCLUSION:We found that dynamic lung compliance decreased significantly upon change of posture from supine to lateral or prone position, whereas in the kneeling position no change in compliance was observed. We suggest that the kneeling position might be preferable to the prone position.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Pulmonary surfactant dysfunction may contribute to the development of ventilator induced lung injury (VILI). Tracheal gas insufflation (TGI) is a technique in which fresh gas is introduced into the trachea and augment ventilation by reducing the dead space of ventilatory system, reducing ventilatory pressures and tidal volume (V(T)) while maintaining constant partial arterial CO2 pressure (PaCO(2)). We hypothesised that TGI limited peak inspiratory pressure (PIP) and V(T) and would minimize conventional mechanical ventilation (CMV) induced pulmonary surfactant dysfunction and thereby attenuate VILI in rabbits with acute lung injury (ALI). METHODS:ALI was induced by intratracheal administration of lipopolysaccharide in anaesthetized, ventilated healthy adult rabbits randomly assigned to continuous TGI at 0.5 L/min (TGI group) or CMV group (n = 8 for each group), and subsequently ventilated with limited PIP and V(T) to maintain PaCO(2) within 35 to 45 mmHg for 4 hours. Physiological dead space to V(T) ratio (V(D)/V(T)), dynamic respiratory compliance (Cdyn) and partial arterial O(2) pressure (PaO(2)) were monitored. After ventilation, lungs were analysed for total phospholipids (TPL), total proteins (TP), pulmonary surfactant small to large aggregates ratio (SA/LA) in bronchoalveolar lavage fluid (BALF) and for determination of alveolar volume density (V(V)), myeloperoxidase and interleukin (IL)-8. RESULTS:TGI resulted in significant (P < 0.05 or P < 0.01) decrease in PIP [(22.4 +/- 1.8) cmH2O vs (29.5 +/- 1.1) cmH2O], V(T) [(6.9 +/- 1.3) ml/kg vs (9.8 +/- 1.11) ml/kg], V(D)/V(T) [(32 +/- 5)% vs (46 +/- 2)%], TP [(109 +/- 22) mg/kg vs (187 +/- 25) mg/kg], SA/LA (2.5 +/- 0.4 vs 5.4 +/- 0.7), myeloperoxidase [(6.2 +/- 0.5) U/g tissue vs (12.3 +/- 0.8) U/g tissue] and IL-8 [(987 +/- 106) ng/g tissue vs (24 +/- 3) mN/m] of BALF, and significant (P < 0.05) increase in Cdyn [(0.47 +/- 0.02) ml.cmH2O(-1).kg(-1) vs (0.31 +/- 0.02) ml.cmH2O(-1).kg(-1)], PaO(2) [(175 +/- 24) mmHg vs (135 +/- 26) mmHg], TPL/TP (52 +/- 8 vs 33 +/- 11) and Vv (0.65 +/- 0.05 vs 0.44 +/- 0.07) as compared with CMV. CONCLUSIONS:In this animal model of ALI, TGI decreased ventilatory requirements (PIP, V(T) and V(D)/V(T)), resulted in more favourable alveolar pulmonary surfactant composition and function and less severity of lung injury than CMV. TGI in combination with pressure limited ventilation may be a lung protective strategy for ALI.

背景与目标：

BACKGROUND & AIMS: :Activating mutations in the tyrosine kinase domain of the HER2 gene have recently been reported in lung adenocarcinomas, mainly in East Asian patients. Our study was devised to evaluate the prevalence and nature of HER2 mutations in lung adenocarcinomas from Caucasian patients. The mutational status of the HER2 gene was evaluated in 403 lung adenocarcinomas by PCR-single strand conformation polymorphism analysis and direct sequencing of Exons 19 and 20. We found HER2 mutations in 9 (2.2%) cases. Seven (78%) of the mutations were in frame duplications/insertions at codons 776-779 (YVMA), the other 2 were base substitutions resulting in aminoacid changes. The hotspot mutation at bases 776-779 was previously found to be the most frequent HER2 mutation in Asiatic patients. The distribution of mutations was significantly different between conventional lung adenocarcinomas (CLAs) and lung adenocarcinomas with bronchioloalveolar features (ABAFs). Seven (6.2%) of 113 ABAFs and 2 (0.7%) of 290 CLA were mutated (p = 0.0025). In addition, the frequency of HER2 mutations was slightly higher in females (4.1%) than in males (1.8%) and in never smokers (3.1%) than in smokers (1.9%), but differences were not statistically significant. This series of tumors was also investigated for EGFR and K-ras mutations. EGFR mutations were observed in 43 (10.7%) cases, and K-ras mutations in 110 (27.3%) cases. EGFR, HER2 and K-ras mutations were found to be mutually exclusive events. The presence of HER2 mutations in a subset of patients with lung adenocarcinoma raise hope to treat these patients with HER2 specific kinase inhibitors.

背景与目标： : 最近在肺腺癌 (主要是东亚患者) 中报道了HER2基因酪氨酸激酶结构域的激活突变。我们的研究旨在评估白种人肺腺癌中HER2突变的患病率和性质。通过PCR-单链构象多态性分析和外显子19和20的直接测序，评估了403例肺腺癌中HER2基因的突变状态。我们在9 (2.2%) 例病例中发现HER2突变。7 (78%) 个突变在密码子776-779 (YVMA) 的帧重复/插入中，另外2个是导致氨基酸变化的碱基取代。先前发现776-779碱基的热点突变是亚洲患者中最常见的HER2突变。在常规肺腺癌 (cras) 和具有细支气管肺泡特征的肺腺癌 (ABAFs) 之间，突变的分布显着不同。113 ABAFs中的7个 (6.2%) 和290 CLA中的2个 (0.7%) 发生突变 (p = 0.0025)。此外，女性 (4.1%) 的HER2突变频率略高于男性 (1.8%)，从不吸烟者 (3.1%) 高于吸烟者 (1.9%)，但差异无统计学意义。还研究了这一系列肿瘤的EGFR和K-ras突变。在43 (10.7%) 例中观察到EGFR突变，在110 (27.3%) 例中观察到K-ras突变。发现EGFR，HER2和K-ras突变是相互排斥的事件。在一部分肺腺癌患者中存在HER2突变，这使人们希望用HER2特异性激酶抑制剂治疗这些患者。

BACKGROUND & AIMS: BACKGROUND:The combination of inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA) is recommended by treatment guidelines for the treatment of persistent asthma. Two such combination products, salmeterol/fluticasone propionate (SFC, Seretide GSK, UK) and formoterol/budesonide (FBC, Symbicort, AstraZeneca, UK) are commercially available. OBJECTIVES:The purpose of these studies was to evaluate and compare the duration of bronchodilation of both combination products up to 24 hours after a single dose. METHODS:Two randomised, double blind, placebo-controlled, crossover studies were performed. Study A was conducted in 33 asthmatic adults receiving 400-1200 mcg of budesonide or equivalent. Serial forced expiratory volume in one second (FEV1) was measured over 24 hours to determine the duration of effect of both SFC (50/100 mcg) and FBC (4.5/160 mcg). Study B was conducted in 75 asthmatic adults receiving 800-1200 mcg of budesonide or equivalent and comprised a 4 week run-in of 400 mcg bd Becotide followed by 4 weeks treatment with either SFC 50/100 mcg bd or FBC 4.5/160 mcg bd taken in a cross-over manner. Serial 24-hour FEV1 was measured after the first dose and the last dose after each 4-weeks treatment period to determine the offset of action of each treatment. RESULTS:In study A, a single inhalation of SFC and FBC produced a sustained bronchodilation at 16 hours with an adjusted mean increase in FEV1 from pre-dose of 0.22 L (95% CI 0.19, 0.35 L) for SFC and 0.25 L (95% CI 0.21, 0.37 L) for FBC, which was significantly greater than placebo for both treatments (-0.05 L; p < 0.001). In study B, the slope of decline in FEV1 from 2-24 hours post dose was -16.0 ml/hr for SFC and -14.2 ml/hr for FBC. The weighted mean AUC over 24 hours was 0.21 Lxmin and 0.22 Lxmin and mean change from pre-dose FEV1 at 12 hours was 0.21 L for SFC and 0.20 L for FBC respectively CONCLUSION:Both SFC and FBC produced a similar sustained bronchodilator effect which was prolonged beyond 12 hours post dose and was clearly measurable at 24 h.

背景与目标：

BACKGROUND & AIMS: :The National Radiological Protection Board's advisory Group on Non-ionising Radiation has recommended further study on the effects of electric charge on the deposition of 0.005-1 microm particles in the lung. Estimates have been made regarding the integrated ion exposure within the corona plume generated by a power line and by ionisers in an intensive care unit. Changes in the charge state of particles with sizes in the range 0.02-13 mum have been calculated for these exposures. The corona plume increases the charge per particle of 0.02 and 0.1 microm particles by the order of 0.1. The ionisers in the intensive care unit produced negative ions-as do power lines under most conditions. Bacteria can carry in the order of 1000 charges (of either sign) and it is shown that the repulsion between such a negatively charged bacterium and negative ions prevents further ion deposition by diffusion charging. Positively charged bacteria can, however, be discharged by the ions which are attracted to them. The data provide no support for the hypothesis that ion exposure, at the levels considered, can increase deposition in the lung.

背景与目标： : 国家放射防护委员会的非电离辐射咨询小组建议进一步研究电荷对肺中0.005-1微米颗粒沉积的影响。已经对由电力线和重症监护病房中的离子发生器产生的电晕羽流中的综合离子暴露进行了估计。对于这些暴露，已经计算了尺寸在0.02-13微米范围内的颗粒的电荷状态变化。电晕羽流使0.02和0.1微米颗粒的每个颗粒的电荷增加0.1数量级。重症监护病房中的离子发生器会产生负离子-在大多数情况下，电源线也是如此。细菌可以以1000电荷的顺序携带 (任一符号)，并且显示出这种带负电荷的细菌与负离子之间的排斥防止通过扩散电荷进一步的离子沉积。但是，带正电的细菌可以被吸引到它们的离子排出。这些数据没有支持这样的假设，即离子暴露在所考虑的水平上会增加肺中的沉积。

BACKGROUND & AIMS: :Sepsis results in a state of relative immunosuppression, rendering critically ill patients susceptible to secondary infections and increased mortality. Monocytes isolated from septic patients and experimental animals display a "deactivated" phenotype, characterized by impaired inflammatory and antimicrobial responses, including hyporesponsiveness to LPS. We investigated the role of the LPS/TLR4 axis and its inhibitor, IL-1 receptor-associated kinase-M (IRAK-M), in modulating the immunosuppression of sepsis using a murine model of peritonitis-induced sepsis followed by secondary challenge by intratracheal Pseudomonasaeruginosa. Septic mice demonstrated impaired alveolar macrophage function and increased mortality when challenged with intratracheal Pseudomonas as compared with nonseptic controls. TLR2 and TLR4 expression was unchanged in the lung following sepsis, whereas levels of IRAK-M were upregulated. Macrophages from IRAK-M-deficient septic mice produced higher levels of proinflammatory cytokines ex vivo and greater costimulatory molecule expression in vivo as compared with those of their WT counterparts. Following sepsis and secondary intrapulmonary bacterial challenge, IRAK-M(-/-) animals had higher survival rates and improved bacterial clearance from lung and blood compared with WT mice. In addition, increased pulmonary chemokine and inflammatory cytokine production was observed in IRAK-M(-/-) animals, leading to enhanced neutrophil recruitment to airspaces. Collectively, these findings indicate that IRAK-M mediates critical aspects of innate immunity that result in an immunocompromised state during sepsis.

背景与目标： 败血症导致相对免疫抑制状态，使重症患者易继发感染并增加死亡率。从败血症患者和实验动物中分离出的单核细胞显示出 “失活” 表型，其特征是炎症和抗菌反应受损，包括对LPS的低反应性。我们研究了LPS/TLR4轴及其抑制剂IL-1受体相关激酶M (IRAK-M) 在调节脓毒症免疫抑制中的作用，该模型使用腹膜炎诱导的脓毒症，然后通过气管内假单胞菌继发攻击的鼠模型。与非败血症对照组相比，败血症小鼠的肺泡巨噬细胞功能受损，死亡率增加。脓毒症后肺中TLR2和TLR4表达不变，而IRAK-M水平上调。与WT对应物相比，来自IRAK-M缺陷脓毒症小鼠的巨噬细胞在体外产生更高水平的促炎细胞因子，并在体内产生更大的共刺激分子表达。与WT小鼠相比，在败血症和继发性肺内细菌攻击后，IRAK-M(-/-) 动物具有更高的存活率，并且从肺和血液中清除细菌。此外，在IRAK-M(-/-) 动物中观察到肺趋化因子和炎性细胞因子的产生增加，导致中性粒细胞向空气空间的募集增强。总的来说，这些发现表明IRAK-M介导了先天免疫的关键方面，从而导致败血症期间的免疫功能低下状态。

BACKGROUND & AIMS: Cytogenetic and molecular genetic studies were performed on a pleomorphic sarcoma removed from the left atrium of a 15-year-old girl. Histologic analysis was consistent with a storiform-pleomorphic malignant fibrous histiocytoma (MFH). Although MFH is the most common soft-tissue sarcoma of late adulthood. It is extremely rare in childhood and its existence in the pediatric population remains controversial. Cytogenetic analysis revealed several alterations previously associated with adult MFH, including abnormalities of chromosomal bands 11p11 and 19p13. Moreover, the tumor demonstrated homogeneously staining regions (HSR) and double minute chromosomes (dmin) suggestive of gene amplification. We therefore screened the case for amplification of genes localized to chromosomal bands 12q13-14, including the putative protooncogenes MDM2, CDK4, SAS, CHOP, and CLI, which are frequently amplified and overexpressed in adult MFH. Southern and Northern blot analysis confirmed the coamplification of MDM2, CDK4, SAS, and CHOP. To our knowledge, such coamplification studies of the 12q13-14 amplicon have not been previously detected in pediatric MFH. Our results provide cytogenetic and molecular genetic evidence that pediatric and adult MFH are histogenetically related entities.

背景与目标： 对一名15岁女孩左心房切除的多形性肉瘤进行了细胞遗传学和分子遗传学研究。组织学分析与多形性恶性纤维组织细胞瘤 (MFH) 一致。尽管MFH是成年后期最常见的软组织肉瘤。在儿童时期极为罕见，其在儿科人群中的存在仍然存在争议。细胞遗传学分析显示了先前与成人MFH相关的几种改变，包括染色体带11p11和19p13的异常。此外，肿瘤显示出均匀染色区域 (HSR) 和双分钟染色体 (dmin)，提示基因扩增。因此，我们筛选了扩增定位于染色体带12q13-14的基因的案例，包括假定的原癌基因MDM2，CDK4，SAS，CHOP和CLI，它们在成年MFH中经常被扩增和过表达。Southern和Northern印迹分析证实了MDM2，CDK4，SAS和CHOP的共扩增。据我们所知，这种12q13-14扩增子的共扩增研究以前尚未在小儿MFH中检测到。我们的结果提供了细胞遗传学和分子遗传学证据，表明儿科和成年MFH是与组织遗传学相关的实体。

BACKGROUND & AIMS: :The distinction between ectopic hamartomatous thymoma and sarcoma is difficult, and preoperative biopsy and intraoperative histopathological examination fail to give a definitive diagnosis. It is important to recognise ectopic hamartomatous thymoma as one of the differential diagnoses of a cervical tumour.

背景与目标： : 异位错构瘤性胸腺瘤和肉瘤之间的区别很困难，术前活检和术中组织病理学检查未能给出明确的诊断。重要的是要认识到异位错构瘤性胸腺瘤是宫颈肿瘤的鉴别诊断之一。

BACKGROUND & AIMS: BACKGROUND:Brain metastasis (BM) is associated with poor prognosis in patients with non-small cell lung cancer (NSCLC). Recent studies demonstrated that microRNA-330-3p (miR-330-3p) was involved in NSCLC brain metastasis (BM). However, the exact parts played by miR-330-3p in BM of NSCLC remain unknown. Discovery and development of biomarkers and elucidation of the mechanism underlying BM in NSCLC is critical for effective prophylactic interventions. Here, we evaluated the expression and biological effects of miR-330-3p in NSCLC cells and explored the underlying mechanism of miR-330-3p in promoting cell migration and invasion in NSCLC. METHODS:Stable over-expression and knockdown of miR-330-3p in NSCLC cells was constructed with lentivirus. Expression levels of miR-330-3p in NSCLC cells were quantified by quantitive real-time PCR (qRT-PCR). The effects of miR-330-3p on NSCLC cells were investigated using assays of cell viability, migration, invasion, cell cycle, apoptosis, western blotting, immunohistochemical, and immunofluorescence staining. A xenograft nude mouse model and in situ brain metastasis model were used to observe tumor growth and brain metastasis. The potential target of miR-330-3p in NSCLC cells was explored using the luciferase reporter assay, qRT-PCR, and western blotting. The miR-330-3p targets were identified using bioinformatics analysis and verified by luciferase reporter assay. The correlation between GRIA3 and DNA methyltransferase (DNMT) 1 and DNMT3A was tested by RT-PCR, western blotting, and co-immunoprecipitation (IP). RESULTS:miR-330-3p was significantly up-regulated in NSCLC cell lines. MTT assay, transwell migration, and invasion assays showed that miR-330-3p promoted the growth, migration, and invasion of NSCLC cells in vitro and induced tumor growth and metastasis in vivo. Luciferase reporter assays showed that GRIA3 was a target of miR-330-3p. qRT-PCR and western blotting exhibited that miR-330-3p promoted the growth, invasion, and migration of NSCLC cells by activating mitogen-activated protein kinase (MAPK)/extracellular-regulated protein kinases (ERK) signaling pathway. Furthermore, miR-330-3p up-regulated the total DNA methylation in NSCLC cells, and co-IP-demonstrated GRIA3 was directly related with DNMT1 and DNMT3A. CONCLUSIONS:miR-330-3p promoted the progression of NSCLC and might be a potential target for the further research of NSCLC brain metastasis.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:To examine the analytic role of arsenic exposure on cancer mortality among the low-dose (well water arsenic level <150 μg/L) villages in the Blackfoot-disease (BFD) endemic area of southwest Taiwan and with respect to the southwest regional data. METHOD:Poisson analyses of the bladder and lung cancer deaths with respect to arsenic exposure (μg/kg/day) for the low-dose (<150 μg/L) villages with exposure defined by the village median, mean, or maximum and with or without regional data. RESULTS:Use of the village median well water arsenic level as the exposure metric introduced misclassification bias by including villages with levels >500 μg/L, but use of the village mean or the maximum did not. Poisson analyses using mean or maximum arsenic levels showed significant negative cancer slope factors for models of bladder cancers and of bladder and lung cancers combined. Inclusion of the southwest Taiwan regional data did not change the findings when the model contained an explanatory variable for non-arsenic differences. A positive slope could only be generated by including the comparison population as a separate data point with the assumption of zero arsenic exposure from drinking water and eliminating the variable for non-arsenic risk factors. CONCLUSION:The cancer rates are higher among the low-dose (<150 μg/L) villages in the BFD area than in the southwest Taiwan region. However, among the low-dose villages in the BFD area, cancer risks suggest a negative association with well water arsenic levels. Positive differences from regional data seem attributable to non-arsenic ecological factors.

背景与目标：