Summary： Alveolar epithelial type II （AT II） cells are essential for lung development and remodeling, as they are precursors for type I cells and also produce other non-repair cells （fibroblasts）. Progenitor ceil...Summary： Alveolar epithelial type II （AT II） cells are essential for lung development and remodeling, as they are precursors for type I cells and also produce other non-repair cells （fibroblasts）. Progenitor ceils are believed to possess capability of multi-potent transdifferentiation, which is closely related to the niche, suggesting the importance of establishment of a lung progenitor cell niche model. We hypothesized that pulmonary surfactant-associated protein A （SPA） suicide gene system would cause AT II cell to kill itself through apoptosis and leave its niche. In vitro, the recombinant adeno-associated virus vectors-SPA-thymidine kinase （rAAV-SPA-TK） system was established to get targeted apoptotic AT II cells. The apoptosis of AT II cells was detected by using MTT. The results showed that cloned SPA gene promoter had specific transcriptional activity in SPA high expression cells, and SPA high expression cells （H441） transfected with TK gene had higher sensitivity to ganciclovir （GCV） than SPA low expression cells （A549）. In vivo, increased apoptosis of AT II cells induced by GCV in rAAV-SPA-TK system was observed by TUNEL. Finally, the successful packaging and application of rAAV-SPA-TK system provide experimental basis to get specific lung progenitor cell （AT II） niche in vitro and in vivo.展开更多
目的检测空泡蛋白分类相关蛋白33A(vacuolar protein sorting-associated protein 33A,VPS33A)在老年肺结核患者外周血中的表达情况,并探讨其与临床预后的相关性。方法收集麻城市人民医院2019年2月~2021年2月收治的95例老年肺结核患者...目的检测空泡蛋白分类相关蛋白33A(vacuolar protein sorting-associated protein 33A,VPS33A)在老年肺结核患者外周血中的表达情况,并探讨其与临床预后的相关性。方法收集麻城市人民医院2019年2月~2021年2月收治的95例老年肺结核患者为研究组,另外选取同期健康体检者90例为对照组。采用实时荧光定量PCR(qRT-PCR)检测外周血中VPS33A,Toll样受体2(TLR2)表达情况,酶联免疫吸附法(ELISA)检测外周血中白细胞介素-6(IL-6)水平。肺结核患者给予标准化抗结核方案治疗(2HRZE/4HR),治疗后随访12个月,根据患者预后将其分为预后良好组(n=58)和预后不良组(n=37),采用受试者工作特征(ROC)曲线分析VPS33A对患者预后不良的预测价值;Pearson法分析预后不良组血清VPS33A与IL-6,TLR2的相关性;Logistic回归分析老年肺结核患者预后不良的影响因素。结果与对照组比较,治疗前研究组外周血VPS33A(0.87±0.22vs1.02±0.23)水平明显降低,IL-6(22.13±5.36 pg/mlvs18.53±4.68pg/ml),TLR2(1.26±0.25vs0.99±0.21)水平明显升高,差异具有统计学意义(t=6.170,6.682,11.241,均P<0.05);与治疗前研究组比较,治疗后研究组外周血VPS33A(0.95±0.25)水平明显升高,IL-6(19.66±5.44 pg/ml),TLR2(1.11±0.2)水平明显降低,差异具有统计学意义(t-3.336,4.648,6.331,均P<0.05)。预后不良组外周血VPS33A水平(0.71±0.16)显著低于预后良好组(0.97±0.22);IL-6(26.41±7.16pg/ml),TLR2(1.35±0.26)水平显著高于预后良好组(19.40±4.21pg/ml,1.20±0.24),差异具有统计学意义(t=5.555,6.012,2.875,均P<0.05)。经Pearson法分析发现,治疗前外周血VPS33A分别与IL-6,TLR2水平呈负相关(r=-0.649,-0.634,均P<0.05)。ROC曲线分析结果显示VPS33A,IL-6和TLR2预测老年肺结核预后的AUC分别为0.805,0.842和0.882,三者联合AUC为0.971,明显高于三者单独预测(Z=4.010,3.136,2.285,P=0.001,0.002,0.022);Logistic回归分析显示外周血VPS33A,IL-6和TLR2是老年肺结核患者预后不良的影响因素(均P<0.05)。结论VPS33A在老年肺结核患者外周血中的表达下调,对老年肺结核患者预后有较好的预测价值,且是预后不良的影响因素。展开更多
目的 分析X-pert联合核苷酸结合寡聚化结构域蛋白2(NOD2)、自噬相关蛋白16样蛋白1(ATG16L1)在活动性肺结核患者疾病转归评估中的应用价值。方法 前瞻性选取2023年4月至2024年4月池州市人民医院收治的110例活动性肺结核患者为研究对象。...目的 分析X-pert联合核苷酸结合寡聚化结构域蛋白2(NOD2)、自噬相关蛋白16样蛋白1(ATG16L1)在活动性肺结核患者疾病转归评估中的应用价值。方法 前瞻性选取2023年4月至2024年4月池州市人民医院收治的110例活动性肺结核患者为研究对象。所有患者均行抗结核治疗、疾病转归评估,将转归患者60例作为转归组,未转归患者50例作为未转归组。收集两组患者的临床资料(年龄、体重指数、性别、吸烟史、贫血、累及肺野数、肺部空洞病变、利福平耐药)。治疗前行X-pert、NOD2、ATG16L1检测,比较两组X-pert阳性率及NOD2、ATG16L1表达水平。采用多因素Logistics回归分析分析活动性肺结核患者疾病转归的影响因素,采用受试者操作特征(ROC)曲线分析X-pert、NOD2、ATG16L1对活动性肺结核患者疾病转归的预测价值。结果 两组体重指数、吸烟史、贫血、累及肺野数、利福平耐药比较,差异均无统计学意义(P>0.05);与转归组相比,未转归组患者年龄较大[(56.15±19.34)vs.(63.18±12.84)岁],男性(71.67 vs. 90.00)%、肺部空洞病变(11.67 vs. 32.00)%比例较高,差异均有统计学意义(P<0.05)。与转归组相比,未转归组患者X-pert阳性率(75.00 vs. 90.00)%、NOD2[(164.31±15.55)vs.(199.29±24.63)ng/L]、ATG16L1[(8.95±1.1.74)vs.(12.15±2.26)ng/L]表达水平均较高,差异均有统计学意义(P<0.05)。多因素Logistics回归分析结果显示,年龄、性别、肺部空洞病变、X-pert、NOD2、ATG16L1为活动性肺结核患者疾病转归的危险因素(P<0.05)。与X-pert、NOD2、ATG16L1单项诊断相比,X-pert、NOD2、ATG16L1联合检测对活动性肺结核患者疾病转归的预测价值较高(P<0.05)。结论 疾病未转归活动性肺结核患者X-pert阳性率、NOD2、ATG16L1表达水平均高于转归患者,X-pert、NOD2、ATG16L1为活动性肺结核患者疾病转归的危险因素,X-pert联合NOD2、ATG16L1对活动性肺结核患者疾病转归的预测价值较高,为活动性肺结核患者疾病转归评估提供了有效依据。展开更多
Objective To evaluate the alterations of biomarkers in the development and progression of coal workers＇ pneumoconiosis （CWP）. Methods The type and number of cells, and the levels of tumor necrosis factor-alpha （T...Objective To evaluate the alterations of biomarkers in the development and progression of coal workers＇ pneumoconiosis （CWP）. Methods The type and number of cells, and the levels of tumor necrosis factor-alpha （TNF-α）, pulmonary surfactant protein, phospholipids and fibronectin in bronchoalveolar lavage fluid were assayed in 14 health active coal miners, 21 coal miners without CWP and 13 miners with CWP of 0/1 to 1/1. Results Compared to active coal miners without CWP （8,23μg/mL）, TNF-α concentration was gradually decreased when dust exposure was stopped （5.90 μg/mL）. Elevated surfactant protein A （SP-A） level and phosphatidylglycerol （PG） to phosphatidylinositol （PI） ratio were found in miners actively exposed to coal dust （6528 μg/mL for SP-A and 10. for PG/P1）, and both parameters decreased when CWP progressed from CWP （0/1） （3419μg/mL for SP-A and 5.9 for PG/PI） to CWP （1/1） （1654 μg/mL for SP-A and 5.5 for PG/PI）. Conclusion Biomarkers in bronchoalveolar lavage fluid can be used to screen coal miners at high risk of developing coal workers＇ pneumoconiosis.展开更多
基金supported by the National Natural Science Foundation of China(No.30500224)
文摘Summary： Alveolar epithelial type II （AT II） cells are essential for lung development and remodeling, as they are precursors for type I cells and also produce other non-repair cells （fibroblasts）. Progenitor ceils are believed to possess capability of multi-potent transdifferentiation, which is closely related to the niche, suggesting the importance of establishment of a lung progenitor cell niche model. We hypothesized that pulmonary surfactant-associated protein A （SPA） suicide gene system would cause AT II cell to kill itself through apoptosis and leave its niche. In vitro, the recombinant adeno-associated virus vectors-SPA-thymidine kinase （rAAV-SPA-TK） system was established to get targeted apoptotic AT II cells. The apoptosis of AT II cells was detected by using MTT. The results showed that cloned SPA gene promoter had specific transcriptional activity in SPA high expression cells, and SPA high expression cells （H441） transfected with TK gene had higher sensitivity to ganciclovir （GCV） than SPA low expression cells （A549）. In vivo, increased apoptosis of AT II cells induced by GCV in rAAV-SPA-TK system was observed by TUNEL. Finally, the successful packaging and application of rAAV-SPA-TK system provide experimental basis to get specific lung progenitor cell （AT II） niche in vitro and in vivo.
文摘目的检测空泡蛋白分类相关蛋白33A(vacuolar protein sorting-associated protein 33A,VPS33A)在老年肺结核患者外周血中的表达情况,并探讨其与临床预后的相关性。方法收集麻城市人民医院2019年2月~2021年2月收治的95例老年肺结核患者为研究组,另外选取同期健康体检者90例为对照组。采用实时荧光定量PCR(qRT-PCR)检测外周血中VPS33A,Toll样受体2(TLR2)表达情况,酶联免疫吸附法(ELISA)检测外周血中白细胞介素-6(IL-6)水平。肺结核患者给予标准化抗结核方案治疗(2HRZE/4HR),治疗后随访12个月,根据患者预后将其分为预后良好组(n=58)和预后不良组(n=37),采用受试者工作特征(ROC)曲线分析VPS33A对患者预后不良的预测价值;Pearson法分析预后不良组血清VPS33A与IL-6,TLR2的相关性;Logistic回归分析老年肺结核患者预后不良的影响因素。结果与对照组比较,治疗前研究组外周血VPS33A(0.87±0.22vs1.02±0.23)水平明显降低,IL-6(22.13±5.36 pg/mlvs18.53±4.68pg/ml),TLR2(1.26±0.25vs0.99±0.21)水平明显升高,差异具有统计学意义(t=6.170,6.682,11.241,均P<0.05);与治疗前研究组比较,治疗后研究组外周血VPS33A(0.95±0.25)水平明显升高,IL-6(19.66±5.44 pg/ml),TLR2(1.11±0.2)水平明显降低,差异具有统计学意义(t-3.336,4.648,6.331,均P<0.05)。预后不良组外周血VPS33A水平(0.71±0.16)显著低于预后良好组(0.97±0.22);IL-6(26.41±7.16pg/ml),TLR2(1.35±0.26)水平显著高于预后良好组(19.40±4.21pg/ml,1.20±0.24),差异具有统计学意义(t=5.555,6.012,2.875,均P<0.05)。经Pearson法分析发现,治疗前外周血VPS33A分别与IL-6,TLR2水平呈负相关(r=-0.649,-0.634,均P<0.05)。ROC曲线分析结果显示VPS33A,IL-6和TLR2预测老年肺结核预后的AUC分别为0.805,0.842和0.882,三者联合AUC为0.971,明显高于三者单独预测(Z=4.010,3.136,2.285,P=0.001,0.002,0.022);Logistic回归分析显示外周血VPS33A,IL-6和TLR2是老年肺结核患者预后不良的影响因素(均P<0.05)。结论VPS33A在老年肺结核患者外周血中的表达下调,对老年肺结核患者预后有较好的预测价值,且是预后不良的影响因素。
文摘目的 分析X-pert联合核苷酸结合寡聚化结构域蛋白2(NOD2)、自噬相关蛋白16样蛋白1(ATG16L1)在活动性肺结核患者疾病转归评估中的应用价值。方法 前瞻性选取2023年4月至2024年4月池州市人民医院收治的110例活动性肺结核患者为研究对象。所有患者均行抗结核治疗、疾病转归评估,将转归患者60例作为转归组,未转归患者50例作为未转归组。收集两组患者的临床资料(年龄、体重指数、性别、吸烟史、贫血、累及肺野数、肺部空洞病变、利福平耐药)。治疗前行X-pert、NOD2、ATG16L1检测,比较两组X-pert阳性率及NOD2、ATG16L1表达水平。采用多因素Logistics回归分析分析活动性肺结核患者疾病转归的影响因素,采用受试者操作特征(ROC)曲线分析X-pert、NOD2、ATG16L1对活动性肺结核患者疾病转归的预测价值。结果 两组体重指数、吸烟史、贫血、累及肺野数、利福平耐药比较,差异均无统计学意义(P>0.05);与转归组相比,未转归组患者年龄较大[(56.15±19.34)vs.(63.18±12.84)岁],男性(71.67 vs. 90.00)%、肺部空洞病变(11.67 vs. 32.00)%比例较高,差异均有统计学意义(P<0.05)。与转归组相比,未转归组患者X-pert阳性率(75.00 vs. 90.00)%、NOD2[(164.31±15.55)vs.(199.29±24.63)ng/L]、ATG16L1[(8.95±1.1.74)vs.(12.15±2.26)ng/L]表达水平均较高,差异均有统计学意义(P<0.05)。多因素Logistics回归分析结果显示,年龄、性别、肺部空洞病变、X-pert、NOD2、ATG16L1为活动性肺结核患者疾病转归的危险因素(P<0.05)。与X-pert、NOD2、ATG16L1单项诊断相比,X-pert、NOD2、ATG16L1联合检测对活动性肺结核患者疾病转归的预测价值较高(P<0.05)。结论 疾病未转归活动性肺结核患者X-pert阳性率、NOD2、ATG16L1表达水平均高于转归患者,X-pert、NOD2、ATG16L1为活动性肺结核患者疾病转归的危险因素,X-pert联合NOD2、ATG16L1对活动性肺结核患者疾病转归的预测价值较高,为活动性肺结核患者疾病转归评估提供了有效依据。
基金This research was supported by University of Essen in Germany and Xishan Coal & Power Company
文摘Objective To evaluate the alterations of biomarkers in the development and progression of coal workers＇ pneumoconiosis （CWP）. Methods The type and number of cells, and the levels of tumor necrosis factor-alpha （TNF-α）, pulmonary surfactant protein, phospholipids and fibronectin in bronchoalveolar lavage fluid were assayed in 14 health active coal miners, 21 coal miners without CWP and 13 miners with CWP of 0/1 to 1/1. Results Compared to active coal miners without CWP （8,23μg/mL）, TNF-α concentration was gradually decreased when dust exposure was stopped （5.90 μg/mL）. Elevated surfactant protein A （SP-A） level and phosphatidylglycerol （PG） to phosphatidylinositol （PI） ratio were found in miners actively exposed to coal dust （6528 μg/mL for SP-A and 10. for PG/P1）, and both parameters decreased when CWP progressed from CWP （0/1） （3419μg/mL for SP-A and 5.9 for PG/PI） to CWP （1/1） （1654 μg/mL for SP-A and 5.5 for PG/PI）. Conclusion Biomarkers in bronchoalveolar lavage fluid can be used to screen coal miners at high risk of developing coal workers＇ pneumoconiosis.
