BackgroundAberrant tissue repair and relentless fibroblast activation are hallmark features of idiopathic pulmonary fibrosis (IPF). Although IPF and Alzheimer’s disease (AD) share underlying aging-related pathologies, including immune and metabolic dysregulation, the putative genetic mechanisms linking AD susceptibility to pathogenic macrophage remodeling in the fibrotic niche are not fully established.MethodsWe performed a two-sample Mendelian randomization (MR) analysis to assess the genetic association and potential causal relationship between AD and IPF. Shared hub genes were identified via protein interaction networks. To characterize macrophage heterogeneity and intercellular crosstalk within the IPF microenvironment, we interrogated scRNA-seq data (GSE122960) utilizing Monocle 3 and CellChat algorithms. The functional essentiality of APOE was evaluated bridging computational virtual knockout (scTenifoldKnk) with laboratory in vitro assays. Specifically, downstream transcriptomic shifts and fibroblast activation capacities were validated using APOE-silenced THP-1 macrophages and a Transwell co-culture model with MRC-5 cells.ResultsMR estimates indicated that genetic liability to AD is associated with a lower risk of developing IPF. Integrated profiling identified the lipid-metabolism gene APOE as a central hub, specifically enriched in lung macrophages. Pseudotime modeling captured a pathogenic bifurcation in IPF, where macrophages evolve toward a terminal state marked by profound oxidative phosphorylation defects and massive SPP1 secretion. These SPP1+ macrophages primarily activate fibroblasts via CD44 and integrin signaling axes. Furthermore, both virtual simulations and in vitro THP-1 experiments demonstrated that loss of APOE function triggers the hyperactivation of complement (C1QA) and antigen-presentation (HLA-DR) pathways. Co-culture assays ultimately confirmed that APOE ablation in macrophages strongly exacerbates myofibroblast differentiation (elevated α-SMA and collagen I) in adjacent MRC-5 cells.ConclusionAPOE functions as a vital metabolic barrier against pro-fibrotic macrophage polarization in the lung. Disruption of this specific lipid metabolic network is strongly associated with SPP1-driven fibroblast activation and local immune imbalance, providing a theoretical framework that strictly warrants future in vivo investigation to determine its clinical relevance.

Idiopathic pulmonary fibrosis (IPF) is an age-related interstitial lung disease of unknown cause. Oxidative stress, an imbalance between oxidants and antioxidants, is implicated in IPF pathogenesis and prognosis but needs further study. We used transcriptome sequencing data (GSE70866) and oxidative stress-related genes from GeneCards. A prognostic risk model for IPF patients was constructed using LASSO. Functional and pathway differences were analyzed between risk score groups, along with comparisons of immune cells and functions. An IPF rat model with vitamin D3 (VD3) intervention was also established. Finally, we used IL-4 to induce M2 macrophages to explore the mechanism of action of CCL2. We identified 483 DEGs and 50 oxidative stress-related DEGs (OSDEGs). Single-factor COX regression identified 34 prognostic OSDEGs, and LASSO identified an 8-gene signature for the risk model. The high-risk group had more CD8 + T cells, macrophages, APC costimulation, and cytokine-cytokine receptor activity. CCL2 was significantly correlated with macrophages in IPF. VD3 inhibited the TGF-β signaling pathway and reduced macrophage M2 infiltration in the rat model. In the IL-4 induced M2 macrophage model, we found that M2 macrophages produced more CCL2, and the production of CCL2 was significantly reduced after VD3 intervention. We established prognostic markers of eight oxidative stress-related genes. The risk score effectively predicts adverse outcomes in IPF. VD3 may alleviate IPF by reducing macrophage infiltration and inhibiting the TGF-β signaling pathway.

Polyethylene terephthalate microplastics (PET-MPs) are persistent in the environment and have become an emerging health concern. PET-MPs play a role in lung pathologies; however, little is known about their role in idiopathic pulmonary fibrosis (IPF). Our research aimed to determine the role of PET-MPs in exacerbating IPF by combining improved detection and toxicology. The ProTox 3.0 platform was used to predict the microplastic toxicity of polyethylene terephthalate. The toxicological mechanism of PET-MP-induced IPF was explored using network toxicology, molecular docking, Mendelian randomization, and single-cell sequencing analysis. By analyzing the PubChem, ChEMBL, and SwissTargetPrediction databases, 120 potential targets related to PET-MPs exposure were identified, and 81 intersecting targets were obtained by intersecting the IPF gene in the Gene Expression Omnibus database. These were further optimized into three core targets, namely AKT1, PIM1, and PIK3CD. PET-MPs affected metabolic, lipid, atherosclerosis, and C-type selection receptor signaling pathways. The binding affinity of PET-MPs to these core targets was potent, and PET-MPs had a good binding effect with these target proteins. PET-MPs exhibit lung toxicity, which may be related to three key proteins: AKT1, PIK3CD, and PIM1. PET-MPs may exacerbate IPF via metabolic pathways, lipids, and atherosclerosis, which may occur in AT2 and CD8+T cells. This study offers valuable information on the molecular mechanism of IPF triggered by PET-MPs, emphasizing the practicality of network toxicology in the toxicity evaluation of emerging environmental contaminants.

Ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation, is implicated in the development and therapeutic responses of cancer. However, the role of ferroptosis-related gene profiles in lung squamous cell carcinoma (LSCC) remains largely unknown. The present study aimed to identify the prognostic roles of ferroptosis-related genes in LSCC. Sequencing data from the Cancer Genome Atlas were analyzed and ferroptosis-related gene expression between tumor and para-tumor tissue was identified. The prognostic role of these genes was also assessed using Kaplan-Meier analyses and univariate and multivariate Cox proportional hazards regression model analyses. Immunological correlation, tumor stemness, drug sensitivity and the transcriptional differences of heat shock protein (HSP)A5 in LSCC were also analyzed. Thereafter, the expression of HSPA5 in 100 patients with metastatic LSCC was evaluated using immunohistochemistry (IHC) and the clinical significance of these markers with different risk factors was assessed. Of the 22 ferroptosis-related genes, the expression of HSPA5, HSPB1, glutathione peroxidase 4, Fanconi anemia complementation group D2, CDGSH iron sulfur domain 1, farnesyl-diphosphate farnesyltransferase 1, nuclear factor erythroid 2 like 2, solute carrier (SLC)1A5, ribosomal protein L8, nuclear receptor coactivator 4, transferrin receptor and SLC7A11 was significantly increased in LSCC compared with adjacent tissues. However, only high expression of HSPA5 was able to predict progression-free survival (PFS) and disease-free survival in LSCC. Although HSPA5 was also significantly elevated in patients with lung adenocarcinoma, HSPA5 expression did not predict the prognosis of patients with lung adenocarcinoma. Of note, a higher expression of HSPA5 was related to higher responses to chemotherapy but not to immunotherapy. In addition, HSPA5 expression was positively correlated with 'ferroptosis', 'cellular responses to hypoxia', 'tumor proliferation signature', 'G2M checkpoint', 'MYC targets' and 'TGFB'. IHC analysis also demonstrated that a high expression of HSPA5 in patients with metastatic LSCC in the study cohort was associated with shorter PFS and overall survival. In conclusion, the present study demonstrated that the expression of the ferroptosis-related gene HSPA5 may be a negative prognostic marker for LSCC.

目的 探究玉屏风散合人参五味子汤与常规西医治疗稳定期慢性阻塞性肺疾病的效果.方法 选取2020年3月至2022年8月郑州大学第五附属医院收治的稳定期慢性阻塞性肺疾病患者92例,随机数表法分为观察组、对照组,各46例.对照组行常规西医治疗,观察组在常规西医基础上加行玉屏风散合人参五味子汤治疗,两组均持续治疗12周.比较两组中医证候评分、呼吸力学状态[总呼吸道黏性阻力(R5)、共振频率(Fres)、肺顺应性(CL)、总顺应性(CT)].结果 ①治疗过程观察组脱落1例、对照组脱落2例,最终观察组45例、对照组44例纳入本研究.②治疗6周、12周,两组患者R5、Fres呈降低趋势(P＜0.05),Cl、Ct提高(P＜0.05);且观察组患者治疗6周、12周的R5、Fres低于对照组,Cl、Ct高于对照组,差异有统计学意义(P＜0.05).结论 常规西医基础上加行玉屏风散合人参五味子汤治疗稳定期慢性阻塞性肺疾病可明显改善患者中医证候及肺功能,调节呼吸力学状态,提高临床疗效.

临床上住院治疗的患者大部分都需要营养支持,但能量预测方程不能准确算出患者的能量需求.因为能量消耗不但受到患者体重、性别、年龄和身高等特征的影响,同时也受到身体状态、体温、营养支持、治疗等因素的影响.目前公认的能够准确反映人体能量代谢的设备是经典的间接热量测量设备,称为代谢车(MC).间接热量代谢车是通过测量二氧化碳产生、氧气消耗,在经过转化得出能量消耗中糖、脂肪、蛋白质三种营养素的组成,从而使人体内三种营养素的代谢保持平衡.本综述主要阐述了营养代谢车的适应症及特点,并针对各种临床情况做出了总结,指出了间接测热法临床应用的局限性,以期为临床更好使用间接测热设备提供一定指导.

Objective:To investigate the drug resistance of carbapenem-resistant Acinetobacter baumannii (CRAb), and to analyze the drug resistance genes of the isolated strains.Methods:A total of 339 CRAb strains isolated from clinical specimens in the Fifth Affiliated Hospital of Zhengzhou University from January 2018 to December 2021 were collected. The resistance of CRAb to commonly used antibiotics was detected by drug sensitivity test. The drug resistance genes of isolated strains were detected by ploymerase chain reaction (PCR) amplification method.Results:The 339 CRAb strains had the highest resistance to amoxicillin/sulbactam, aztreonam, cefepime, gentamicin and piperacillin, but had the highest sensitivity to tigecycline and polymyxin B. Results of PCR amplification found that OXA-23 (83.14%), OXA-51 (77.01%), ADC (73.56%) and VIM (15.71%) were main drug resistance genes. One to seven kinds of drug resistance genes were detected in each strain, and strains with 5 kinds of drug resistance genes were the majority (81 strains, 31.03%).Conclusions:There are some characteristics in drug resistance of CRAb strains. OXA-23, OXA-51, ADC and VIM are main drug resistance genes. Prevention and control measures for nosocomial infection should be strengthened in clinical.

目的 探讨痰热清注射液联合注射用头孢哌酮钠舒巴坦钠治疗重症肺炎的临床疗效.方法 选取2019年6月—2021年6月郑州大学第五附属医院收治的87例重症肺炎患者,按照随机数字表法将所有患者分为对照组(43例)和治疗组(44例).对照组静脉滴注注射用头孢哌酮舒巴坦钠,3.0 g/次,2次/d.治疗组在对照组基础上静脉滴注痰热清注射液,20 mL加入500 mL葡萄糖注射液中,1次/d.两组患者连续治疗14 d.观察两组的治疗效果,比较两组患者主要症状的消失时间、肺部感染程度和血清炎症因子水平.结果 治疗后,治疗组患者的总有效率(95.45％)高于对照组的总有效率(81.40％)(P<0.05).治疗后,治疗组发热、咳嗽、肺啰音、肺部阴影消失时间均短于对照组(P<0.05).治疗后,两组的临床肺部感染评分(CPIS)显著降低(P<0.05),且治疗组CPIS明显低于对照组(P<0.05).治疗后,两组的中性粒细胞与淋巴细胞比值(NLR)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)水平显著降低(P<0.05),且治疗组NLR、IL-6、IL-8水平比对照组降低更明显(P<0.05).结论 痰热清注射液联合注射用头孢哌酮钠舒巴坦钠可提高重症肺炎的临床疗效,能加快主要症状改善,减轻肺感染程度和炎症反应,药物安全性良好.

目的 探讨结肠癌转移相关基因1(MACC1)与肺鳞状细胞癌和肺腺癌细胞顺铂耐药性的关系.方法 收集2018年1月至2019年12月郑州大学第五附属医院手术切除的新鲜肺腺癌组织标本37例和肺鳞状细胞癌组织标本23例,所有患者术前未行放射治疗和化学治疗.取新鲜癌组织行原代细胞体外培养.取第2代肺鳞状细胞癌和肺腺癌细胞,将癌细胞分别均分为顺铂组和对照组,顺铂组细胞以含顺铂的培养液继续培养72 h,对照组细胞按原代细胞培养液继续培养72 h,采用甲基噻唑基四唑(MTT)法检测肺鳞状细胞癌和肺腺癌细胞对顺铂的敏感性.取新鲜癌组织,采用免疫组织化学染色检测肺腺癌和肺鳞状细胞癌组织中MACC1蛋白的表达.取第2代肺鳞状细胞癌和肺腺癌细胞,反转录-聚合酶链反应法检测肺腺癌和肺鳞状细胞癌细胞中MACC1 mRNA的表达.结果 37例肺腺癌患者对顺铂的敏感率为59.46％(22/37),耐药率为40.54％(15/37);23例肺鳞状细胞癌患者对顺铂的敏感率为52.17％(12/23),耐药率为47.83％(11/23);肺腺癌与肺鳞状细胞癌患者对顺铂的敏感性比较差异无统计学意义(χ2=2.849,P>0.05).高、中、低分化肺腺癌对顺铂的耐药率分别为41.67％(5/12)、42.11％(8/19)、33.33％(2/6),高、中、低分化肺腺癌对顺铂的耐药率比较差异无统计学意义(χ2=2.916,P>0.05),高、中、低分化肺鳞状细胞癌对顺铂的耐药率分别为50.00％(2/4)、46.67％(7/15)、50.00％(2/4),高、中、低分化肺鳞状细胞癌对顺铂的耐药率比较差异无统计学意义(χ2=1.527,P>0.05);高、中、低分化的肺腺癌与肺鳞状细胞癌对顺铂的耐药率比较差异均无统计学意义(χ2=2.014、1.034、1.679,P>0.05).Ⅰ、Ⅱ、Ⅲa、Ⅲb、Ⅳ期肺腺癌对顺铂的耐药率分别为0.00％(0/2)、33.33％(1/3)、36.36％(4/11)、38.46％(5/13)、62.50％(5/8);随着TNM分期升高,肺腺癌对顺铂的耐药率升高(χ2=21.417,P<0.05).Ⅰ、Ⅱ、Ⅲa、Ⅲb、Ⅳ期肺鳞状细胞癌对顺铂的耐药率分别为0.00％(0/1)、33.33％(1/3)、44.44％(4/9)、50.00％(4/8)、100.00％(2/2);随着TNM分期升高,肺鳞状细胞癌对顺铂的耐药率升高(χ2=19.034,P<0.05).Ⅰ、Ⅱ、Ⅲa期肺腺癌与肺鳞状细胞癌对顺铂的耐药率比较差异无统计学意义(χ2=2.327、0.159、0.827,P>0.05);Ⅲb、Ⅳ期肺腺癌对顺铂的耐药率显著低于肺鳞状细胞癌(χ2=8.361、10.357,P<0.05).肺腺癌和肺鳞状细胞癌组织中MACC1蛋白表达比较差异无统计学意义(χ2=3.119,P>0.05).肺腺癌和肺鳞状细胞癌细胞中MACC1 mRNA相对表达量分别为1.217±0.012、1.137±0.011,肺腺癌与肺鳞状细胞癌细胞中MACC1 mRNA相对表达量比较差异无统计学意义(t=12.137,P>0.05).肺腺癌和肺鳞状细胞癌组织中MACC1蛋白表达与顺铂耐药性呈正相关(r=0.747、0.681,P<0.05).结论 肺腺癌和肺鳞状细胞癌对顺铂的耐药率较高,肺腺癌和肺鳞状细胞癌组织中MACC1蛋白表达与顺铂耐药性呈正相关,MACC1可能参与了肺腺癌和肺鳞状细胞癌对顺铂耐药的发生机制.

目的 本研究旨在探索脓毒症患者中外周血JNK通路磷酸酶(JKAP)水平与Th1、Th17细胞的关联性,以及它们与脓毒症患病风险和死亡风险的关系.方法 连续纳入79例脓毒症患者和80例健康受试者(对照),采集外周血后分离血清及CD4+T细胞,采用酶联免疫吸附测定法检测血清JKAP和炎症因子水平,采用流式细胞术检测CD4+T细胞中Th1和Th17比率.结果 脓毒症患者中JKAP水平相比较对照显著降低(P<0.001),而Th1(P<0.001)和Th17(P<0.001)细胞比率相较于对照显著升高.进一步受试者工作曲线分析表明JKAP、Th1和Th17细胞水平均可以较好地区分脓毒症患者和对照者.脓毒症患者中,JKAP水平与Th1、Th17细胞比率,TNF-α、IL-1β和IL-17均呈负相关(均P<0.05),并且与APACHEⅡ评分(P<0.001)和SOFA评分也呈负相关(P<0.001).此外,脓毒症死亡患者JKAP水平低于生存患者(P<0.001),Th1(P=0.001)和Th17(P=0.001)细胞水平在脓毒症死亡患者中高于生存患者;进一步受试者工作曲线分析表明三者均可以一定程度预测脓毒症患者死亡风险.结论 JKAP与Th1、Th17细胞高度相关,并且有作为脓毒症患病风险、疾病严重程度监控及短期预后生物标志物的潜能.

目的 探讨血清胱抑素C(CysC)、血管内皮生长因子(VEGF)、白细胞介素17(IL-17)、激活素A(ACTA)在老年慢性阻塞性肺疾病(COPD)伴严重呼吸衰竭患者中的表达.方法 选取2016年3月至2019年3月本院224例老年COPD患者,根据有无发生严重呼吸衰竭分组观察组(n=78)、轻症组(n=146),另选取同期健康体检者86例为对照组.比较3组不同预后患者血清CysC、VEGF、IL-17、ACTA水平,分析血清指标对老年COPD伴严重呼吸衰竭的诊断价值及血清指标间相关性,并分析血清指标与APACHEⅡ评分相关性及预后预测价值.结果 3组血清CysC、VEGF、IL-17、ACTA水平,差异有统计学意义(P＜0.05);VEGF与Cys C、IL-17、ACTA水平呈负相关,CysC、IL-17、ACTA间水平呈正相关(P＜0.05);死亡患者血清CysC、IL-17、ACTA水平、APACHEⅡ评分高于存活患者,VEGF水平低于存活患者(P＜0.05);VEGF水平与APACHEⅡ评分呈负相关,CysC、IL-17、ACTA水平与APACHEⅡ评分呈正相关(P＜0.05);血清CysC、VEGF、IL-17、ACTA水平联合对预测老年COPD伴严重呼吸衰竭预后的AUC(0.864)大于单一血清指标,敏感性为92.86％,特异性为70.00％.结论 血清CysC、VEGF、IL-17、ACTA水平在老年COPD伴严重呼吸衰竭患者中呈异常表达,并与病情密切相关,联合检测有望成为老年COPD伴严重呼吸衰竭诊断及预后判断的有效手段.

Certain high-risk factors related to the death of COVID-19 have been reported, however, there were few studies on a death prediction model. This study was conducted to delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) of different degree and establish a death prediction model. In this multi-centered, retrospective, observational study, we enrolled 523 COVID-19 cases discharged before February 20, 2020 in Henan Province, China, compared clinical data, screened for high-risk fatal factors, built a death prediction model and validated the model in 429 mild cases, six fatal cases discharged after February 16, 2020 from Henan and 14 cases from Wuhan. Out of the 523 cases, 429 were mild, 78 severe survivors, 16 non-survivors. The non-survivors with median age 71 were older and had more comorbidities than the mild and severe survivors. Non-survivors had a relatively delay in hospitalization, with higher white blood cell count, neutrophil percentage, D-dimer, LDH, BNP, and PCT levels and lower proportion of eosinophils, lymphocytes and albumin. Discriminative models were constructed by using random forest with 16 non-survivors and 78 severe survivors. Age was the leading risk factors for poor prognosis, with AUC of 0.907 (95% CI 0.831-0.983). Mixed model constructed with combination of age, demographics, symptoms, and laboratory findings at admission had better performance (p= 0.021) with a generalized AUC of 0.9852 (95% CI 0.961-1). We chose 0.441 as death prediction threshold (with 0.85 sensitivity and 0.987 specificity) and validated the model in 429 mild cases, six fatal cases discharged after February 16, 2020 from Henan and 14 cases from Wuhan successfully. Mixed model can accurately predict clinical outcomes of COVID-19 patients.

Objective:To explore the effect of non-invasive ventilation in patients with chronic obstructive pulmonary disease (COPD) managed by general practitioners and specialists.Methods:A total of 64 patients with COPD and respiratory failure in stable period in the Fifth Affiliated Hospital of Zhengzhou University from December 2017 to December 2018 were selected and randomly divided into two groups by computer blind selection method: the family non-invasive ventilator ventilation group (observation group) and the natural course control group (control group), with 32 cases in each group. The patients were followed up by general practitioners and respiratory specialists once every three months and understood the situation of patients, discussed the parameters of ventilator, guided the application of ventilator, and monitored the pulmonary function indexes dynamically such as forced expiratory volume per second (FEV1% pred), blood gas analysis indexes such as blood gas analysis indicators (pH value, pulse oxygen saturation (SpO 2), arterial oxygen sub-pressure (PaO 2), arterial blood carbon dioxide sub-pressure (PaCO 2), modified British Medical Research Council (mMRC) dyspnea scales, and the number of acute exacerbations within 1 year. Results:After 1 year of treatment, SpO 2, PaO 2 and mMRC scales were improved compared with the control group, with statistically significant differences ( P<0.05), and the number of acute seizures decreased compared with the control group, and the difference was statistically significant ( P<0.05), but there was no significant difference in FEV1% pred, PaCO 2 and pH value( P>0.05). Conclusions:The combination of general practitioners and specialists in the management of noninvasive ventilation at home can significantly improve the arterial oxygen partial pressure of COPD patients, improve the degree of dyspnea and reduce the number of acute cases.

目的 观察无创通气联合布地奈德福莫特罗粉吸入剂治疗慢性阻塞性肺疾病急性加重期(AECOPD)合并呼吸衰竭的效果,并了解血清4-羟基壬烯醛(4-HNE)、血管内皮细胞生长因子(VEGF)水平的变化情况.方法 选取郑州大学第五附属医院2016年5月至2018年9月76例AECOPD合并呼吸衰竭患者,采用随机数表法分为两组.对照组38例接受无创呼吸机干预,观察组38例接受布地奈德福莫特罗联合无创呼吸机治疗,通过比较两组血气分析指标[动脉血氧分压(PaO2)、动脉血二氧化碳分压(PaCO2)]、肺功能指标[第1秒用力呼气容积(FEV1)、FEV1与用力肺活量的比值(FEV1/FEC)]及生活质量评分(QOL)等观察临床疗效,并观察血清4-HNE、VEGF水平变化情况.结果 观察组治疗总有效率为89.47％(34/38),高于对照组的68.42％(26/38),差异有统计学意义(P<0.05).治疗3个月后,观察组及对照组与同组治疗前比较,各项指标均有改善(均P<0.05),且观察组PaO2及FEV1、FEV1/FVC均高于对照组,PaCO2低于对照组,差异有统计学意义(均P<0.05).观察组血清4-HNE、VEGF水平均低于对照组,差异有统计学意义(均P<0.05).观察组治疗3个月后QOL评分高于对照组,差异有统计学意义(P<0.05).结论 无创呼吸机联合布地奈德福莫特罗粉吸入剂可改善AECOPD合并呼吸衰竭患者临床症状、血气分析指标及血清4-HNE、VEGF水平,有助于患者肺功能恢复,提高生活质量.

目的 探讨siRNA沉默结肠癌转移相关基因1(MACC1)表达对耐药性非小细胞肺癌细胞株A549增殖及侵袭的影响.方法 培养非耐药性和耐药性非小细胞肺癌A549细胞,应用RT-PCR技术检测MACC1 mRNA的表达水平;通过化学合成特异性siRNA,与阳离子脂质体Lipofectamine 2000形成复合体,转染耐药性A549细胞,RT-PCR检测转染效果;继续顺铂药物处理耐药性A549细胞,MTT法检测细胞增殖抑制率;Hoechst33258染色法观察siMACC1后耐药性A549细胞的凋亡形态;Transwell法检测siMACC1后耐药性A549细胞迁移能力;Western blot法检测siMACC1后耐药性A549细胞周期蛋白E-cadherin和N-cadherin的表达水平.结果 与耐药性A549细胞组比较,非耐药性A549细胞组中MACC1 mRNA表达量显著下降(P＜0.05).与siRNA NC耐药性A549细胞组比较,siRNA MACC1耐药性A549细胞组中MACC1 mRNA表达量显著降低(P＜0.05),细胞增殖抑制率上升(P＜0.05);Hoechst 33258细胞染色结果表明siRNA MACC1耐药性A549细胞组发生细胞皱缩,细胞核聚集,细胞形态学呈现细胞凋亡改变;Transwell实验表明MACC1基因沉默后,细胞迁移能力变弱;Western blot结果表明MACC1基因沉默后,与siRNA NC耐药性A549细胞组比较,siRNA MACC1耐药性A549细胞组中E-cadherin蛋白表达显著增加(P＜0.05),N-cadherin蛋白表达显著减少(P＜0.05),细胞的侵袭转移能力显著减弱.结论 MACC1在耐药性A549细胞中的异常升高,可能是肺癌肿瘤细胞耐药性产生的分子机制之一.siRNA MACC1能够有效转染耐药性A549细胞,能显著地抑制耐药性A549细胞增殖与侵袭.

目的 探讨替米沙坦激活的过氧化物酶体增殖物激活受体 γ(PPARγ)对大鼠肺动脉高压的影响及其机制.方法 皮下注射野百合碱复制大鼠肺动脉高压模型,将大鼠分为模型组、治疗组、干预组及对照组.治疗组每天给予替米沙坦10 mg/kg灌胃处理,模型组不予治疗,干预组在治疗组基础上给予GW96625 mg/kg腹腔注射.3周后取材,测量各组大鼠右心室收缩压(RVSP),肺动脉平均压(mPAP),计算右心室肥大指数(RVHI),苏木精-伊红染色观察肺动脉炎症反应情况,酶联免疫吸附试验检测肺组织匀浆中TNF-α、IL-6、单核细胞趋化蛋白-1(MCP-1)水平,Western blotting检测PPARγ 表达差异.结果 4组mPAP、RVSP及RVHI比较,差异有统计学意义(P<0.05),模型组较对照组高(P<0.05),治疗组、干预组较模型组低(P<0.05),干预组RVHI高于治疗组(P<0.05).模型组和干预组PPARγ 相对表达量较对照组降低(P<0.05),治疗组较模型组升高(P<0.05).模型组、治疗组、干预组MCP-1、IL-6及TNF-α 水平较对照组升高(P<0.05),治疗组、干预组较模型组降低(P<0.05),干预组较治疗组升高(P<0.05).结论 替米沙坦对野百合碱诱导的大鼠肺动脉高压有预防作用,可能与其激活PPARγ,抑制炎症反应有关.

目的:研究瑞芬太尼联合咪达唑仑对重症颅脑损伤(SCI)患者镇静及脑代谢的临床效果.方法:选择2015年8月～2018年8月在本院接受治疗的120例SCI患者作为研究对象,依据不同治疗措施将其分为联合组(咪达唑仑注射液+注射用盐酸瑞芬太尼)和对照组(咪达唑仑注射液)各60例.治疗结束后观察比较两组RASS评分、Ricker镇静-躁动(SAS)评分、平均动脉压(MAP)、心率(HR)、中心静脉压(CVP)、动脉血氧饱和度(SaO2)、颈静脉血氧饱和度(SjvO2)、动脉血氧分压(PaO2)、颈静脉血氧分压(PjvO2)、脑氧代谢率(CMRO2)、不良反应发生率,所有数据采用SPSS 23.0软件进行统计分析.结果:治疗前,两组RASS评分、SAS评分、MAP、HR、CVP、SaO2、SjvO2、PaO2、PjvO2、CMRO2无统计学差异(P>0.05);治疗后,两组SAS评分、MAP、HR、CVP水平与治疗前比较有所下降,两组RASS评分、SaO2、SjvO2、PaO2、PjvO2、CMRO2水平与治疗前比较有所上升,具有统计学差异(P<0.05);治疗后,联合组SAS评分、MAP、HR、CVP水平低于对照组,RASS评分、SaO2、SjvO2、PaO2、PjvO2、CMRO2水平高于对照组,具有统计学差异(P<0.05);联合组不良反应发生率(8.33％)低于对照组(21.67％),具有统计学差异(P<0.05).结论:瑞芬太尼联合咪达唑仑对SCI患者具有良好的镇静效果,能有效改善患者血流动力学及血气状态,从而使脑代谢恢复正常,安全性高,值得临床推广应用.

Objective To investigate the changes of hypoxia-inducible factor (HIF-1α, HIF-2α) expression level in lung cancer A-549 cells under normoxic conditions, different hypoxia durations, and different oxygen concentrations. Methods A549 cells were divided into normoxic group, time control group, and oxygen concentration control group. Western blot was used to detect the expression of HIF-1α and HIF-2α in A-549 cells.Results The expression of HIF-1α and HIF-2α protein were lower under normoxia and significantly increased under hypoxic conditions. The difference was statistically significant. The lower the oxygen concentration, the more HIF-1α and HIF-2α protein expression levels were. The differences between high and high were statistically significant. The expression of HIF-1α protein increased at 2 h after hypoxia, peaked at 8 h, appeared plateau at 8 to 16 h, and decreased at 32 h, with a statistically significant difference. HIF-2α proteins gradually increased with prolonged hypoxia. Conclusions Under hypoxic conditions, the expression of HIF-1α and HIF-2α are increased, and the expression of HIF-2α has a time-dependent pattern, which may have more important biological significance.

目的:探讨黄芪注射液联合丹参注射液治疗慢性阻塞性肺疾病的临床效果及对患者氧化应激水平的影响.方法:采用随机数字表法将137例慢性阻塞性肺疾病急性加重期(A EC O-PD)患者分为对照组68例和观察组69例.对照组给予常规治疗,观察组在对照组的基础上给予黄芪注射液联合丹参注射液治疗.观察两组治疗前后第1秒用力呼气量(FEV1)、用力肺活量(FVC)、FEV1占FVC的百分比(FEV1/FVC%)、血清超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)和总抗氧化能力(T-AOC)水平,统计两组临床疗效.结果:观察组有效率显著高于对照组,差异有统计学意义(P<0.05).两组治疗后FEVE1、FEV1/FVC水平与治疗前相比较均显著升高(P<0.05),且观察组与同期对照组相比较均显著升高(P<0.05).两组治疗后SOD、GSH-Px、T-AOC水平与治疗前相比较均显著升高(P<0.05),且观察组与同期对照组相比较均显著升高(P<0.05);两组治疗后MDA水平与治疗前相比较均显著降低(P<0.05),且观察组与同期对照组相比较显著降低(P<0.05).结论:黄芪注射液联合丹参注射液治疗AECO-PD可改善患者肺功能,提高治疗效果,清除氧自由基和提高抗氧化能力可能是其重要作用机制.