慢性阻塞性肺疾病急性发作期患者肠道菌群特征及血清同型半胱氨酸、白介素-6对其肠道菌群失调的预测效能

分析慢性阻塞性肺疾病急性发作期（AECOPD）患者肠道菌群特征及血清同型半胱氨酸（Hcy）、白介素-6（IL-6）对患者肠道菌群失调的预测效能。

将2020年1月至2022年1月我院收治的96例AECOPD患者纳入研究组,另选同期健康体检者88例作为对照组。所有纳入对象入院后均采集血液、粪便样本检测血清Hcy、IL-6水平及肠道菌群。比较两组对象血清Hcy、IL-6水平及肠道菌群数量差异。采用受试者工作特性曲线（ROC）分析血清Hcy、IL-6对AECOPD患者肠道菌群失调的预测效能,同时采用单因素、多因素Logistic回归分析探讨影响AECOPD患者肠道菌群失调的相关因素。

研究组患者肠道双歧杆菌、乳杆菌数量均显著低于对照组（t = −10.167、−4.045,均P＜0.001）,大肠埃希菌、肠球菌数量均显著高于对照组（t = 8.493、8.440,均P＜0.001）。96例AECOPD患者肠道菌群失调发生率为36.45%（35/96）。与对照组血清Hcy[（10.76±3.23）μmol/L]、IL-6[（0.86±0.35）mg/L]水平相比较,肠道菌群失调组AECOPD患者血清Hcy[（38.65±5.41）μmol/L]、IL-6[（132.55±25.62）mg/L]水平和肠道菌群正常组患者血清Hcy[（20.22±4.18）μmol/L]、IL-6[（40.58±6.69）mg/L]水平均显著升高（t = 28.543、30.408、14.865、46.327,均P＜0.001）,且肠道菌群失调组AECOPD患者血清Hcy、IL-6水平均显著高于肠道菌群正常组（t = 18.641、25.664,均P＜0.001）。ROC曲线显示,血清Hcy预测AECOPD患者肠道菌群失调的曲线下面积为0.771,截断值为29.50 μmol/L,灵敏度、特异度分别为92.62%、58.62%;IL-6预测AECOPD患者肠道菌群失调的曲线下面积为0.752,截断值为88.69 mg/L,灵敏度、特异度分别为92.62%、65.34%;血清Hcy联合IL-6预测AECOPD患者肠道菌群失调的曲线下面积为0.901,灵敏度、特异度分别为86.04%、87.65%。多因素Logistic回归分析显示,血清Hcy[OR（95% CI） = 3.904（2.049～7.440）]、IL-6[OR（95% CI） = 3.414（1.926～6.052）]及急性加重次数≥2次/年[OR（95% CI） = 3.404（1.936～5.986）]均为影响AECOPD患者肠道菌群失调的相关因素。

AECOPD患者存在肠道菌群失调,且主要表现为双歧杆菌、乳杆菌减少及大肠埃希菌、肠球菌增多,其发生与血清Hcy、IL-6水平密切相关,血清Hcy、IL-6水平的升高可作为预测AECOPD患者肠道菌群失调的有效指标。

     

肠内营养乳剂TPF-D联合微生态制剂对慢性阻塞性肺疾病急性加重期患者心肺功能和营养指标的影响

探讨肠内营养乳剂TPF-D联合微生态制剂对慢性阻塞性肺疾病急性加重期（AECOPD）患者心肺功能及营养指标的影响,为该类患者的治疗提供参考。

选取2020年7月至2021年5月我院收治的108例AECOPD患者为研究对象,依据随机数表法将患者分为观察组及对照组,各54例。两组患者均接受常规治疗与护理,对照组患者给予肠内营养乳剂TPF-D,观察组患者在对照组的基础上给予微生态制剂,两组患者均治疗2周。比较患者肠黏膜屏障功能指标[肠型脂肪酸结合蛋白（I-FABP）、二胺氧化酶（DAO）]、炎症反应指标[白细胞（WBC）、降钙素原（PCT）、C-反应蛋白（CRP）]、营养指标[白蛋白（ALB）、前白蛋白（PA）]、心肺功能指标[左心室射血分数（LVEF）、氧耗量（VO₂）、二氧化碳生成量（VCO₂）、呼吸商（RQ）、每分钟通气量（VE）、NT-proBNP]、消化道并发症发生率（应激性溃疡、腹胀、腹泻、胃潴留、便秘等）。

观察组患者治疗后I-FABP和DAO水平低于对照组（t = 17.533、8.469,均P＜0.05）。观察组患者治疗后WBC、CRP和PCT水平低于对照组（t = 14.997、18.710、23.197,均P＜0.05）。观察组患者治疗后PA和ALB水平高于对照组（t = 8.083、7.292,均P＜0.05）。观察组患者治疗后LVEF水平高于对照组（t = 3.862,P＜0.05）。观察组患者治疗后VO₂、VCO₂、RQ、VE和TN-proBNP水平均低于对照组（t = 3.923、12.569、7.292、3.095、10.079,均P＜0.05）。观察组患者腹胀、腹泻、胃潴留发生率均低于对照组（χ² = 4.441、4.821、4.216,均P＜0.05）。

肠内营养乳剂TPF-D结合微生态制剂有利于改善AECOPD患者黏膜屏障功能,抑制炎症反应,增强患者心肺功能,改善患者营养状态,降低消化道并发症发生率。

     

Duvelisib attenuates bleomycin‐induced pulmonary fibrosis via inhibiting the PI3K/Akt/mTOR signalling pathway

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease that seriously threatens the health of patients. The pathogenesis of IPF is still unclear, and there is a lack of effective therapeutic drugs. Myofibroblasts are the main effector cells of IPF, leading to excessive deposition of extracellular matrix (ECM) and promoting the progression of fibrosis. Inhibiting the excessive activation and relieving autophagy blockage of myofibroblasts is the key to treat IPF. PI3K/Akt/mTOR pathway plays a key regulatory role in promoting fibroblast activation and autophagy inhibition in lung fibrosis. Duvelisib is a PI3K inhibitor that can simultaneously inhibit the activities of PI3K‐δ and PI3K‐γ, and is mainly used for the treatment of relapsed/refractory chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma tumour (SLL). In this study, we aimed to examine the effects of Duvelisib on pulmonary fibrosis. We used a mouse model of bleomycin‐induced pulmonary fibrosis to evaluate the effects of Duvelisib on pulmonary fibrosis in vivo and further explored the potential pharmacological mechanisms of Duvelisib in lung fibroblasts in vitro. The in vivo experiments showed that Duvelisib significantly alleviated bleomycin‐induced collagen deposition and improved pulmonary function. In vitro and in vivo pharmacological experiments showed that Duvelisib dose‐dependently suppressed lung fibroblast activation and improved autophagy inhibition by inhibiting the phosphorylation of PI3K, Akt and mTOR. Our results indicate that Duvelisib can alleviate the severity of pulmonary fibrosis and provide potential drugs for the treatment of pulmonary fibrosis.     

低氧对培养的肺血管周细胞凋亡的影响

为了研究低氧是否影响肺血管周细胞凋亡并参与腺泡内无肌肺动脉的构型重建, 用ＴＵＮＥＬ法和免疫组化方法, 观察低氧（Ｈ） 组和低氧肺动脉内皮细胞条件培养液（ＨＥＣＣＭ） 组对肺血管周细胞凋亡发生率及抑凋亡基因ｂｃｌ２ 蛋白表达的影响。结果表明：Ｈ组和ＨＥＣＣＭ 组的凋亡指数明显较对照组减小。Ｈ 组和ＨＥＣＣＭ 组ｂｃｌ２ 蛋白的表达量分别是ＮＥＣＣＭ 组的１１７ 倍、１１３ 倍, 是Ｎ组的１３３ 倍、１２７ 倍。提示低氧诱导的抑凋亡基因ｂｃｌ２ 的过度表达, 对周细胞凋亡发生的抑制作用和低氧促进的周细胞增生过程可能都参与无肌肺动脉的构型重建, 与肺动脉高压的形成有关。     

Oceanic sinks for atmospheric CO2

There is approximately 50 times more inorganic carbon in the global ocean than in the atmosphere. On time scales of decades to millions of years, the interaction between these two geophysical fluids determines atmospheric CO₂ levels. During glacial periods, for example, the ocean serves as the major sink for atmospheric CO₂, while during glacial–interglacial transitions, it is a source of CO₂ to the atmosphere. The mechanisms responsible for determining the sign of the net exchange of CO₂ between the ocean and the atmosphere remain unresolved. There is evidence that during glacial periods, phytoplankton primary productivity increased, leading to an enhanced sedimentation of particulate organic carbon into the ocean interior. The stimulation of primary production in glacial episodes can be correlated with increased inputs of nutrients limiting productivity, especially aeolian iron. Iron directly enhances primary production in high nutrient (nitrate and phosphate) regions of the ocean, of which the Southern Ocean is the most important. This trace element can also enhance nitrogen fixation, and thereby indirectly stimulate primary production throughout the low nutrient regions of the central ocean basins. While the export flux of organic carbon to the ocean interior was enhanced during glacial periods, this process does not fully account for the sequestration of atmospheric CO₂. Heterotrophic oxidation of the newly formed organic carbon, forming weak acids, would have hydrolyzed CaCO₃ in the sediments, increasing thereby oceanic alkalinity which, in turn, would have promoted the drawdown of atmospheric CO₂. This latter mechanism is consistent with the stable carbon isotope pattern derived from air trapped in ice cores. The oceans have also played a major role as a sink for up to 30% of the anthropogenic CO₂ produced during the industrial revolution. In large part this is due to CO₂ solution in the surface ocean; however, some, poorly quantified fraction is a result of increased new production due to anthropogenic inputs of combined N, P and Fe. Based on ‘circulation as usual’, models predict that future anthropogenic CO₂ inputs to the atmosphere will, in part, continue to be sequestered in the ocean. Human intervention (large-scale Fe fertilization; direct CO₂ burial in the deep ocean) could increase carbon sequestration in the oceans, but could also result in unpredicted environmental perturbations. Changes in the oceanic thermohaline circulation as a result of global climate change would greatly alter the predictions of C sequestration that are possible on a ‘circulation as usual’ basis.     

新型气液双升式动物细胞反应器

为克服目前动物细胞反应器存在的不足 ,设计了一种新型气液双升式动物细胞反应器( ALLR)。该反应器结合了气升式反应器和流化床反应器的优点 ,同时在结构上使气泡与流体自然流动与分离 ,消除了气泡凝聚破裂给细胞造成的机械损伤。测定了 2 L反应器的液体循环流速及氧传质系数 KLa值 ,表明 ALLR具有较好的传质性能和极小的流体剪切力 ,适合动物细胞的大规模培养     

牛肺动脉单层内皮细胞长度与其血管紧张素II代谢的相关性

用离体培养的牛肺动脉内皮细胞灌流实验研究内皮细胞单层长度与其血管紧张素II代谢的相关性。牛肺动脉单层内皮细胞暴露于剪应力为0.64N/m2 的剪切流中24h后 ,两种不同长度(10cm和6cm)单层内皮细胞的血管紧张素II的平均分泌率有比较显著差异 ,10cm处理的血管紧张素II平均分泌率 (8.61±0.28pg/cm2.h)比6cm处理 (6.14±0.12pg/cm2.h)高40 % ,10cm处理的最小分泌率 (7.55pg/cm2.h)较6cm处理 (5.75pg/cm2.h)高31 % ,10cm处理的最小分泌率出现的剪切时间点比6cm处理要早6个小时。表明牛肺动脉内皮细胞单层长度与其血管紧张素II代谢 (分泌率 )间有密切的相关关系 ,进而从细胞代谢角度间接证实血管内皮细胞膜张应力存在累积效应。     

下呼吸道重开的生物流体力学研究:实验模拟

实验模拟了受阻塞肺下呼吸道重开的生物力学问题。呼吸是玻璃直圆管,以具有生物流体性质的机油作为阻塞液。实验给同了在压强差作用下阻塞液柱前陈面以及主粘液柱气泡前阵面的位置和速度曲线。结果表明,它们受外加压强,管直径,阻塞液以及初始阻塞液长度的影响。较高的外加中、阻塞液粘度较你攻管径较粗有利于呼吸道的重开。     

肺动脉管壁Ⅰ.Ⅲ型胶原变化在慢性低O2高CO2肺动脉高压形成中的作用

目的 :探讨管壁胶原及Ⅰ、Ⅲ型胶原变化在慢性低O2 高CO2 性肺动脉高压形成中的作用。方法 :采用透射电镜、图像分析及免疫组化等方法 ,研究四周低O2 高CO2 对大鼠肺动脉压力和管壁胶原及Ⅰ、Ⅲ型胶原的影响 ,肺动脉壁I和III型胶原的平均积分吸光度值作为Ⅰ、Ⅲ型胶原的相对含量。结果 :①低O2 高CO2 组 (B组 )大鼠肺动脉平均压 (MPAP)显著高于对照组 (P <0 .0 1) ,颈动脉平均压 (MCAP)无明显变化 (P >0 .0 5 ) ;②电镜下 ,低O2 高CO2 大鼠肺细小动脉中膜平滑肌细胞明显增生 ,面积增大 ,其间胶原纤维丰富 ,外膜纤维母细胞增生 ,胶原纤维高度密集。免疫组化发现低O2 高CO2 大鼠肺细小动脉管壁Ⅰ型胶原平均吸光度值较对照组明显增高 (P <0 .0 1) ,Ⅲ型胶原平均吸光度值两组间无明显差异 (P >0 .0 5 ) ;③低O2 高CO2 组大鼠血浆内皮素浓度较对照组明显升高(P <0 .0 1) ,血清一氧化氮 (NO)较对照组明显减低 (P <0 .0 1)。结论 :肺动脉壁的胶原含量增多 (Ⅰ型胶原增多 )与慢性低O2 高CO2 性肺动脉高压的形成以及肺动脉结构重建有关 ,一氧化氮和内皮素可能起介导作用