胸膜肺母细胞瘤2例并文献复习

目的:探讨胸膜肺母细胞瘤临床病理学特征、诊断及鉴别.材料与方法:对2例小儿胸膜肺母细胞瘤进行组织形态学和免疫组织化学检查,结合临床资料进行分析并随访.结果:胸膜肺母细胞瘤是一种间质性的恶性肿瘤,常见于儿童及婴幼儿,肿瘤细胞为起源于肺、胸膜或纵膈的原始细胞;镜下表现:肿块包括囊性变及实性肿块,囊性主要为原始间叶性小细胞,结节状实性区主要为未分化的卵圆形及星芒状细胞成分.结论:胸膜肺母细胞瘤是一种极为罕见的恶性肿瘤,主要依靠病理学形态及免疫组化进行诊断,应与肺母细胞瘤、胚胎性横纹肌肉瘤等鉴别.     

罕见肺母细胞瘤1例

肺母细胞瘤(pulmonary blastoma,PB)又称肺胚胎瘤或胚胎性癌肉瘤,是一种临床罕见,恶性程度很高的肿瘤。病情发展迅速,预后差。我科收治1例,报道如下。     

儿童先天性肺囊肿的CT诊断

<正>儿童先天性肺囊肿是一种较常见的先天性肺发育畸形,在胚胎发育期,由于气管和支气管异常萌芽或分支而形成囊肿。本文通过分析18例先天性肺囊肿的CT表现特点,结合临床表现,旨在提高对本病的CT诊断和鉴别诊断水平。     

肺隔离症患者围手术期护理体会

<正>肺隔离症是一种少见的先天性发育异常性疾病,为胚胎时期一部分肺组织与正常肺分离而单独发育,由起源于主动脉的一支异常动脉供血,且无肺功能的先天性支气管肺发育异常[1]。根据隔离的肺与正常肺有无共同胸膜分为叶内型和叶外型,叶内型占75%。本病缺乏典型的临床表     

FGF-10与肺的形态发生和损伤修复研究进展

间充质-上皮之间的交互作用贯穿着胚胎器官发育与成熟的整个过程,成纤维细胞生长因子(FGF)在此过程中起着重要的调控作用,尤其是FGF-10,众多研究表明,它是整个胚胎器官发育过程中必不可少的一员.近年来,FGF-10在胚胎支气管-肺的形态发生和分支作用以及在支气管-肺上皮损伤修复过程中的作用尤其引人注目,本文针对其在这方面的调控作用作一综述.     

多层螺旋CT双期增强扫描在肺隔离症诊断中的应用

<正>肺隔离症(pulmonary sequestration,PS)又称隔离肺,是一种少见的先天性发育异常性疾病,占肺部疾病的0.15%～6.4%,为胚胎时期一部分肺组织与正常肺分离而单独发育,由起源于主动脉的一支异常动脉供血,且无肺功能的先天性支气管肺发育异常[1]。术前正确诊断是治疗此     

盐酸川芎嗪注射液对内毒素引起小鼠急性肺损伤的保护作用

目的：观察川芎嗪对内毒素引起小鼠急性肺损伤的保护作用。方法：建立内毒素急性损伤小鼠肺病理模型，造模4和8h后，应用川芎嗪进行治疗，造模24h后，对血细胞和肺灌洗液中细胞计数、测定肺灌洗液中蛋白酶活性和蛋白含量。结果：腹腔注射川芎嗪对血液成分没有明显影响，但可以使肺灌洗液中自细胞、粒细胞、单核细胞的含量有所降低，增加淋巴细胞数比例，抑制弹性蛋白酶的生成或活性。结论：川芎嗪可调节机体组织免疫功能，具有一定的肺保护作用，可以缓解由于内毒素或类似物质造成的肺部炎症。     

蛹虫草提取物对内毒素引起小鼠急性肺损伤的保护作用

目的 :观察蛹虫草提取物对内毒素引起小鼠急性肺损伤的保护作用。方法 :建立内毒素急性损伤小鼠肺病理模型 ,造模 4和 8h后 ,用蛹虫草提取物治疗 ,造模 2 4h后 ,对血细胞和肺灌洗液中细胞进行计数并测定肺灌洗液中蛋白酶的活性和蛋白的含量。结果 :蛹虫草提取物对血液成分没有明显影响 ,但可以使肺灌洗液中白细胞、粒细胞的含量有所降低 ,而淋巴细胞和单核细胞的数量有所增加 ,蛋白酶活性降低。结论 :蛹虫草提取物可调节机体组织的免疫功能 ,可以缓解由于内毒素或类似物质造成的肺部炎症 ,具有一定的肺保护作用。     

肺发育不良的CT诊断与鉴别诊断

肺不发育为完全性单侧或双侧肺缺如，没有任何肺实质、支气管和血管供应的痕迹。有时仅见到残留的支气管，呈现一囊袋状盲端，而没有肺血管和肺实质，该肺不发育有人称为成形不全。而两侧肺发育不全者多于出生后即死亡。肺发育不良为部分或全部肺的血管、气管和肺泡的数目减少，或两者同时存在；可见于一侧肺或一叶肺也可以双侧多叶肺累及。     

肺隔离症的诊断和治疗

肺隔离症（pulmonary sequestration，PS）是一类先天性肺发育畸形的疾病，该病的主要特点是在胚胎时期，部分肺组织与主体肺分离，单独发育形成囊性肿块，接受体循环动脉供血，不具备肺的功能。根据异常组织有无完整的胸膜与正常肺组织分界，通常分为叶内型（intralobars equestration，IIS）和叶外型（extralobarse questratiou，EIS）。     

Prenatal nicotine exposure enhances the susceptibility to metabolic syndrome in adult offspring rats fed high-fat diet via alteration of HPA axis-associated neuroendocrine metabolic programming

Aim： Prenatal nicotine exposure （PNE） alters the hypothalamic-pituitary-adrenocortical （HPA） axis-associated neuroendocrine metabolic programming in intrauterine growth retardation offspring rats. In this study we aimed to clarify the susceptibility to metabolic diseases of PNE offspring rats fed a high-fat diet. Methods： Maternal Wistar rats were injected with nicotine （1.0 mg/kg, sc） twice per day from gestational day 11 until full-term delivery, and all pups were fed a high-fat diet after weaning and exposed to unpredictable chronic stress （UCS） during postnatal weeks 18-20. Blood samples were collected before and after chronic stress, and serum ACTH, corticosterone, glucose, insulin, total cholesterol, triglyceride and free fatty acids levels were measured. The hypothalamus, pituitary gland and liver were dissected for histological studies. Results： UCS significantly increased the serum ACTH, corticosterone and insulin levels as well as the insulin resistant index without changing the serum glucose, total cholesterol, triglyceride and free fatty acids levels in adult offspring rats without PNE. The body weight of PNE offspring rats presented a typical ＂catch-up＂ growth pattern. PNE not only aggravated the UCS-induced changes in the HPA axis programmed alteration （caused further increases in the serum ACTH and corticosterone levels）, but also significantly changed the glucose and lipid metabolism after UCS （caused further increases in the serum glucose level and insulin resistant index, and decrease in the serum free fatty acids）. The effects of PNE on the above indexes after UCS showed gender differences. Pathological studies revealed that PNE led to plenty of lipid droplets in multiple organs. Conclusion： PNE enhances not only the HPA axis, but also the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet after UCS in a gender-specific manner and enhances the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet.     

Stereoselective binding of doxazosin enantiomers to plasma proteins from rats,dogs and humans in vitro

Aim： （＋）Doxazosin is a long-lasting inhibitor of a1-adrenoceptors that is widely used to treat benign prostatic hyperplasia and lower urinary tract symptoms. In this study we investigated the stereoselective binding of doxazosin enantiomers to the plasma proteins of rats, dogs and humans in vitro. Methods： Human, dog and rat plasma were prepared. Equilibrium dialysis was used to determine the plasma protein binding of each enantiomer in vitro. Chiral HPLC with fluorescence detection was used to measure the drug concentrations on each side of the dialysis membrane bag. Results： Both the enantiomers were highly bound to the plasma proteins of rats, dogs and humans [（-）doxazosin： 89.4%-94.3%; （＋）doxazosin： 90.9%-95.4%]. （＋）Doxazosin exhibited significantly higher protein binding capacities than （-）doxazosin in all the three species, and the difference in the bound concentration （Cb） between the two enantiomers was enhanced as their concentrations were increased. Although the percentage of the plasma protein binding in the dog plasma was significantly lower than that in the human plasma at 400 and 800 ng/mL, the corrected percentage of plasma protein binding was dog〉human〉rat. Conclusion： （-）Doxazosin and （＋）doxazosin show stereoselective plasma protein binding with a significant species difference among rats, dogs and humans.     

Hsp90 inhibitor BILBO21 enhances triptolide-induced apoptosis of human T-cell acute lymphoblastic leukemia cells in vitro mainly by disrupting p53- MDM2 balance

Aim： To investigate the effects of BILBO21, an inhibitor of heat shock protein 90 （Hsp90） alone or in combination with triptolide （TPL） on T-cell acute lymphoblastic leukemia （T-ALL） and the mechanisms of action. Methods： Human T-ALL cells line Molt-4 was examined. The cell viability was measured using M]-I- assay. Apoptotic cells were studied with Hoechst 33258 staining. Cell apoptosis and cell cycle were analyzed using flow cytometry with Annexin V/PI staining and PI staining, respectively. The levels of multiple proteins, including Akt, p65, CDK4/6, p18, Bcl-2 family proteins, MDM2, and p53, were examined with Western blotting. The level of MDM2 mRNA was determined using RT-PCR. Results： Treatment of Molt-4 cells with BILBO21 （50-800 nmol/L） inhibited the cell growth in a dose-dependent manner （the IC~ovalue was 384.6 and 301.8 nmol/L, respectively, at 48 and 72 h）. BILBO21 dose-dependently induced Go/G1 phase arrest, followed by apoptosis of Molt-4 cells. Furthermore, BILBO21 increased the expression of p18, decreased the expression of CDK4/6, and activated the caspase pathway in Molt-4 cells. Moreover, BILBO21 （50-400 nmol/L） dose-dependently decreased the phospho-MDM2 and total MDM2 protein levels, but slightly increased the phospho-p53 and total p53 protein levels, whereas TPL （5-40 nmol/L） dose- dependently enhanced p53 activation without affecting MDM2 levels. Co-treatment with BILBO21 and TPL showed synergic inhibition on Molt-4 cell growth. The co-treatment disrupted p53-MDM2 balance, thus markedly enhanced p53 activation. In addition, the co-treatment increased the expression of Bak and Bim, followed by increased activation of caspase-9. Conclusion： The combination of BILBO21 and TPL may provide a novel strategy for treating T-ALL by overcoming multiple mechanisms of apoptosis resistance.     

肺癌生物治疗的研究现状及进展

肺癌的发病率高居恶性肿瘤之首,是恶性肿瘤病死率中增长最快,危害最大的之一。尽管近年来的化疗药物层出不穷,但疗效方面仍然处于难以突破的平台期。近年来肿瘤生物疗法作为辅助疗法,可消除患者体内残存的肿瘤细胞,针     

美国与欧洲上市后药品安全风险管理进展概述

近10年来,美国食品药品管理局（FDA）、欧洲药品管理局（EMA）及其他相关单位,对上市后药品安全性监测日益重视,在这一领域取得了显著进展,并且制定了一系列新规定。     

厄洛替尼治疗晚期非小细胞肺癌的研究进展

肺癌是最常见的恶性肿瘤之一,在全世界范围内,其发病率和死亡率均呈上升趋势,严重的威胁着人类的健康。其中非小细胞肺癌(NSCLC)约占肺癌总发病率的85%,就诊时75%的患者已是局部晚期或有远处转移[1]。对于晚期N S C L C,一般状况好,铂类双药联合化疗是标准     

Sodium hydrosulfide alleviates lung inflammation and cell apoptosis following resuscitated hemorrhagic shock in rats

Aim： To investigate the protective effects of hydrogen sulfide （H2S） against inflammation, oxidative stress and apoptosis in a rat model of resuscitated hemorrhagic shock. Methods： Hemorrhagic shock was induced in adult male SD rats by drawing blood from the femoral artery for 10 min. The mean arterial pressure was maintained at 35-40 mmHg for 1.5 h. After resuscitation the animals were observed for 200 min, and then killed. The lungs were harvested and bronchoalveolar lavage fluid was prepared. The levels of relevant proteins were examined using Western blotting and immunohistochemical analyses. NariS （28 pmol/kg, ip） was injected before the resuscitation. Results： Resuscitated hemorrhagic shock induced lung inflammatory responses and significantly increased the levels of inflammatory cytokines IL-6, TNF-a, and HMGB1 in bronchoalveolar lavage fluid. Furthermore, resuscitated hemorrhagic shock caused marked oxidative stress in lung tissue as shown by significant increases in the production of reactive oxygen species H202 and OH, the translocation of Nrf2, an important regulator of antioxidant expression, into nucleus, and the decrease of thioredoxin I expression. Moreover, resuscitated hemorrhagic shock markedly increased the expression of death receptor Fas and Fas-ligand and the number apoptotic cells in lung tissue, as well as the expression of pro-apoptotic proteins FADD, active-caspase 3, active-caspase 8, Bax, and decreased the expression of Bcl-2. Injection with NariS significantly attenuated these pathophysiological abnormalities induced by the resuscitated hemorrhagic shock. Conclusion： NariS administration protects rat lungs against inflammatory responses induced by resuscitated hemorrhagic shock via suppressing oxidative stress and the Fas/FasL apoptotic signaling pathway.     

靶向治疗在非小细胞肺癌治疗中的应用进展

肺癌是目前全世界最主要的癌症死因之一,肺癌中80%-85%是非小细胞肺癌(non-small cell lung cancer,NSCLC)。NSCLC恶性程度较高,易复发、转移,超过半数以上的患者在确诊时已属相对晚期,如果不治疗,一年的生存期不足10%[1]。肺癌的治疗模式和药物选择正日趋多样化。传统化疗和放疗缺乏特异性,取得疗效的同时也带     

Molecular modeling,quantum polarized ligand docking and structure-based 3D-QSAR analysis of the imidazole series as dual AT~ and ETA receptor antagonists

Aim： Both endothelin ETA receptor antagonists and angiotensin AT1 receptor antagonists lower blood pressure in hypertensive patients. A dual AT1 and ETA receptor antagonist may be more efficacious antihypertensive drug. In this study we identified the mode and mechanism of binding of imidazole series of compounds as dual AT1 and ETA receptor antagonists. Methods： Molecular modeling approach combining quantum-polarized ligand docking （QPLD）, MM/GBSA free-energy calculation and 3D-QSAR analysis was used to evaluate 24 compounds as dual AT1 and ETA receptor antagonists and to reveal their binding modes and structural basis of the inhibitory activity. Pharmacophore-based virtual screening and docking studies were performed to identify more potent dual antagonists. Results： 3D-QSAR models of the imidazole compounds were developed from the conformer generated by QPLD, and the resulting models showed a good correlation between the predicted and experimental activity. The visualization of the 3D-QSAR model in the context of the compounds under study revealed the details of the structure-activity relationship： substitution of methoxymethyl and cyclooctanone might increase the activity against AT~ receptor, while substitution of cyclohexone and trimethylpyrrolidinone was important for the activity against ETA receptor; addition of a trimethylpyrrolidinone to compound 9 significantly reduced its activity against AT~ receptor but significantly increased its activity against ETA receptor, which was likely due to the larger size and higher intensities of the H-bond donor and acceptor regions in the active site of ETA receptor. Pharmacophore-based virtual screening followed by subsequent Glide SP, XP, QPLD and MM/GBSA calculation identified 5 potential lead compounds that might act as dual AT1 and ETA receptor antagonists. Conclusion： This study may provide some insights into the development of novel potent dual ETA and AT1 receptor antagonists. As a result, five compounds are found to be the best dual antagonists against AT1R and ETA receptors.