Effect of perfusate temperature on pulmonary vascular resistance and compliance by arterial and venous occlusion in the rat

The effect of different temperatures of perfusing fluid was tested on the pulmonary circulation of the rat. With increasing temperature, a decrease in overall pulmonary vascular resistance was observed, which depended on the associated reductions of arterial, venous and capillary vascular resistances. The highest sensitivity to temperature changes was exhibited by the venous segment. The overall sensitivity of pulmonary vessels to temperature caused a reduction in hydraulic resistance of about 1% for each 1°C temperature increment. Compliance of pulmonary vessels increased when perfusate temperature was increased from between 25 and 35°C to 45°C, probably due to a direct effect of temperature on the stiffness of the vessel walls.     

肺淋巴管平滑肌瘤病临床病理学观察

目的 探讨肺淋巴管平滑肌瘤病临床、病理特征。方法 对5例肺淋巴管平滑肌瘤病临床资料进行收集分析,HE切片观察,采用免疫组织化学(SP法)检测平滑肌肌动蛋白(SMA)、HMB45、基质金属蛋白酶(MMP)2、孕激素受体(PR)、雌激素受体(ER),并进行文献复习。结果 肺淋巴管平滑肌瘤病是原因不明的肺部疾病,只发生在女性,特别是绝经前妇女。临床表现为呼吸困难,咯血,气胸和乳糜胸等。病理学检查显示不同成熟度平滑肌细胞在细支气管壁、肺泡壁、淋巴管壁和血管壁周围增生,肺实质呈囊性变。增生的平滑肌细胞免疫组织化学5例SMA、HMB45、MMP2均阳性;1例的ER和PR均阳性,1例仅ER阳性,1例仅PR阳性,1例的ER和PR均阴性。结论 育龄期妇女如反复出现自发性气胸、咯血、活动后呼吸困难应考虑肺淋巴管平滑肌瘤病的可能,病理检查可确定肺淋巴管平滑肌瘤病的诊断。     

急性肺血栓栓塞症兔TNF-α、IL-8、IL-10水平及地塞米松的影响

目的:探讨兔急性肺血栓栓塞症(PTE)时血浆及支气管肺泡灌洗液(BALF)中TNF-α,IL-8、IL-10的水平和地塞米松(Dex)的影响。方法:采用自体血栓回输法建立兔急性PTF模型。36只兔随机分为对照组、Dex治疗组和PTE模型组。用ELISA方法检测上述细胞因子(CK)水平,术毕肺组织行病理观察。结果:栓塞后上述CK均有升高,治疗后TNF-α、IL-8均有下降,IL-10变化不明显。组织病理学可见栓塞后肺动脉内血栓形成,肺组织萎缩、出血、炎性反应明显,Dex治疗后肺组织病理改变明显减轻。结论:PTE后促炎性CK在引起肺部炎性反应和肺组织及肺动脉病损中起了重要作用,抗炎治疗可以明显减轻CK引起的这种损伤。抗炎治疗能降低PTE急性期病死率,改善远期预后,CK可能起了很重要的作用。     

西拉普利对低氧大鼠肺动脉和心肌细胞增殖的抑制作用

目的：探索cilazapril 对低氧大鼠肺血管和心肌细胞增殖的抑制机理。 方法： 采用生化、放射免疫、免疫组织化学、细胞凋亡标记和血流动力学技术研究低氧肺血管及心肌细胞增殖和结构重建。 结果： （1）低氧大鼠mPAP显著增高，伴有肺动脉血管管腔狭窄、管壁增厚，心肌肥大，R/L+S增高。（2）B组、C组大鼠肺动脉和右心肌细胞增殖指数（PI）均分别明显高于A组，而C组明显低于B组。ET-1免疫组化染色阳性细胞主要分布在肺动脉血管壁和心肌细胞上，染色程度由强到弱依次为B组>C组>A组。（3）B组大鼠ET-1水平和ACE活性明显高于A组，而C组显著低于B组。（4）直线相关分析显示ET-1、ACE分别与R/(L+S)、mPAP、肺动脉PI、心肌PI呈正相关；多元回归分析显示ET-1和ACE可能是影响PI的主要因素。 结论： 低氧大鼠存在细胞过度增殖状态，继发肺血管、右心结构重建是低氧性肺动脉高压发病机理之一。Cilazapril通过抑制ACE和ET-1的促增殖作用，阻止肺血管及心肌重建，对低氧性肺动脉高压的防治有一定作用。     

儿童青少年甲状腺结节诊断思路

甲状腺结节的发病率随年龄的增加而增加,其检出率取决于受检对象和检查方法的敏感性。儿童可触及甲状腺结节者约为1.5%,成人则为4%～7%[1];甲状腺超声检查的检出率为40%[2],而尸体解剖的相关研究显示,50.5%受检者可检出甲状腺结节[3]。大多数成人甲状腺结节是良     

The effects of different doses of inhaled bacteriophage therapy for Pseudomonas aeruginosa pulmonary infections in mice

ObjectivesInhaled phage therapy has been revisited as a potential treatment option for respiratory infections caused by multidrug-resistant Pseudomonas aeruginosa; however, there is a distinct gap in understanding the dose–response effect. The aim of this study was to investigate the dose–response effect of Pseudomonas-targeting phage PEV31 delivered by the pulmonary route in a mouse lung infection model.MethodsNeutropenic BALB/c mice were infected with multidrug-resistant P. aeruginosa (2 × 10⁴ colony-forming units) through the intratracheal route and then treated with PEV31 at three different doses of 7.5 × 10⁴ (Group A), 5 × 10⁶ (Group B), and 5 × 10⁸ (Group C) plaque-forming units, or phosphate-buffered saline at 2 hours postinoculation. Mice (n = 5–7) were euthanized at 2 hours and 24 hours postinfection, and lungs, kidneys, spleen, liver, bronchoalveolar lavage fluid, and blood were collected for bacteria and phage enumeration.ResultsAt 24 hours postinfection, all phage-treated groups exhibited a significant reduction in pulmonary bacterial load by 1.3–1.9 log₁₀, independent of the delivered phage dose. The extent of phage replication was negatively correlated with the dose administered, with log₁₀ titre increases of 6.2, 2.7, and 9 for Groups A, B, and C, respectively. Phage-resistant bacterial subpopulations in the lung homogenate samples harvested at 24 hours postinfection increased with the treatment dose (i.e. 30%, 74%, and 91% in respective Groups A–C). However, the mutants showed increased susceptibility to ciprofloxacin, impaired twitching motility, and reduced blue-green pigment production. The expression of the inflammatory cytokines (IL-1ß and IL-6, and TNF-α) was suppressed with increasing PEV31 treatment dose.DiscussionThis study provides the dose–response effect of inhaled phage therapy that may guide dose selection for treating P. aeruginosa respiratory infections in humans.     

Succesful MEK-inhibition of severe hypertrophic cardiomyopathy in RIT1-related Noonan Syndrome

Infants with Noonan Syndrome and hypertrophic cardiomyopathy have a poor prognosis and a high mortality especially when diagnosed before six months of age. As for the majority of the RASopathies, no medical treatment has been approved for Noonan Syndrome. Meanwhile, several approved agents targeting the same RAS/MAPK signaling pathway are used in cancer treatment. In this case report we describe a child with Noonan Syndrome caused by a pathogenic RIT1 variant, who developed severe early-onset hypertrophic cardiomyopathy and pulmonary valve stenosis. She received off-label treatment with the MEK-inhibitor trametinib which resulted in complete remission of the cardiac hypertrophy and a significant improvement of the pulmonary valve stenosis. Our case emphasizes the potential of existing cancer agents targeting the RAS/MAPK signaling pathway as successful treatment for RASopathy manifestations.     

三七总皂苷通过Notch3/Hes-1/p27Kip1信号通路抑制低氧性肺动脉高压大鼠肺血管重构

目的：探讨Notch3/Hes-1/p27^Kip1信号通路与低氧性肺动脉高压大鼠肺血管重构的关系及三七总皂苷(PNS)的干预作用。方法：将SPF级雄性SD大鼠采用随机编号分为3组：正常组(C组),低氧组(H组)和PNS组(P组),检测肺动脉压,称量右心室重量,HE染色和Masson染色观察肺血管重构情况,RT-qPCR检测大鼠肺组织中Notch3、Hes-1和p27^Kip1的mRNA表达水平,Western blot检测大鼠肺组织中Notch3、Hes-1、p27^Kip1,增殖细胞核抗原(PCNA)和caspase-3的蛋白水平。结果：与C组相比,H组大鼠的肺动脉压和右心室肥厚指数明显增加;肺血管重构现象明显;Notch3、Hes-1和PCNA的蛋白水平增加,p27^Kip1和caspase-3的蛋白水平降低;Notch3和Hes-1的mRNA表达增加,p27^Kip1的mRNA表达降低(P<0.05)。经PNS干预后,与H组相比,P组大鼠的肺动脉压和右心室肥厚指数降低;肺血...