Prognosis of Connective Tissue Disease Related Interstitial Lung Disease after Initiation of Long-Term Oxygen Therapy: Comparison with Idiopathic Pulmonary Fibrosis

Objective: The studies of long-term oxygen therapy (LTOT) for patents with connective tissue disease-related interstitial lung disease (CTD-ILD) are limited. This study aimed to evaluate the prognosis of CTD-ILD patients following the initiation of LTOT, compared to those with idiopathic pulmonary fibrosis (IPF). Methods: We conducted a retrospective analysis of patients with CTD-ILD and IPF who were introduced to LTOT between January 2014 and December 2020. Results: The study included 24 patients with CTD-ILD and 55 patients with IPF. At the initiation of LTOT, female gender, never-smoking history, higher body mass index (BMI), higher lactate dehydrogenase (LDH) level, lower pulmonary Surfactant Protein-D (SP-D) level and lower Gender-Age-Physiology (GAP) scores were more common in the CTD-ILD group (all Conclusion: Although patients with CTD-ILD had longer overall survival than those with IPF, there was no significant difference in prognosis after the initiation of LTOT between the two groups. Early intervention including treatment and management will be needed in CTD-ILD as in IPF.

Effects of Qishi Shengjiang Guiyuan Granules on Inflammatory Response and T Lymphocyte Subsets in Peripheral Blood of Rats with GERD-Associated Idiopathic Pulmonary Fibrosis

[Objectives] To explore the effects of Qishi Shengjiang Guiyuan Granules on inflammatory response and T lymphocyte subsets in peripheral blood of rats with idiopathic pulmonary fibrosis (IFP) associated with gastroesophageal reflux disease (GERD).[Methods] Twenty-four SPF SD rats were randomly divided into control group, model group, Chinese medicine group and western medicine group, with 6 rats in each group. Except the control group, the other three groups were used to establish the rat model of GERD combined with IPF by injecting hydrochloric acid into the lower end of esophagus and inhaling diluted bleomycin (5 mg/kg). Rats in the Chinese medicine group (14 g/kg), rats in the western medicine group (4.17 g/kg), rats in the control group and the model group were given the same volume of saline by gavage for 14 d. Morphological and pathological changes of esophageal and lung tissues were observed under light microscope, and T lymphocyte subsets (CD_(3)^(+), CD_(4)^(+), CD_(8)^(+)) and the ratio of CD_(4)^(+)/CD_(8)^(+) in peripheral blood were detected by flow cytometry.[Results] Compared with the control group, the pulmonary tissue of the model group showed that the pulmonary interstitium was obviously thickened, the alveoli were mutually fused, the structure was obviously destroyed, the original alveolar structure was disappeared, the inflammatory cell infiltration was around the pulmonary capillaries and the alveolar space, and the basal cell hyperplasia and inflammatory cell infiltration were at the lower end of the esophagus. Compared with the model group, the degree of inflammatory cell infiltration and lung tissue damage in the Chinese medicine group and the western medicine group was significantly reduced, the inflammatory infiltration in the lower esophagus was significantly reduced, and the cell proliferation was reduced. Compared with the control group, the CD_(3)^(+), CD_(4)^(+), CD_(8)^(+), CD_(4)^(+)/CD_(8)^(+) in the peripheral blood of the rats in the model group, the Chinese medicine group and the western medicine group decreased ( P <0.01). Compared with the model group, CD_(3)^(+), CD_(4)^(+), and CD_(4)^(+)/CD_(8)^(+) increased ( P >0.05, P >0.05, P <0.01), CD_(8)^(+) decreased ( P >0.05). Compared with the Chinese medicine group, CD_(3)^(+), CD_(4)^(+), and CD_(4)^(+)/CD_(8)^(+) increased ( P >0.05, P >0.05, P <0.01) and CD_(8)^(+) decreased ( P >0.05) in the western medicine group.[Conclusions] Qishi Shengjiang Guiyuan Granules can effectively improve the inflammation of the lower esophagus and lung tissues of the pulmonary fibrosis rats with GERD and IFP, and regulate the number of T lymphocyte subsets CD_(3)^(+), CD_(4)^(+), CD_(8)^(+) cells and CD_(4)^(+)/CD_(8)^(+) ratio in peripheral blood.

Research progress of Chinese medicine in treatment of IPF(idiopathic pulmonary fibrosis)

Idiopathic pulmonary interstitial fibrosis is one of the respiratory refractory diseases,and the incidence rate is on the rise.At present,the effect of western medicine is not ideal and the side effects are obvious,while the traditional Chinese medicine shows good curative effect on the disease.This paper makes a summary on the traditional Chinese medicine theory in treating idiopathic pulmonary interstitial fibrosis in recent years.

The Expression of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Idiopathic Interstitisal Pneumonia

Background: Idiopathic interstitial pneumonia is characterized by fibroblast proliferation and extracellular matrix (ECM) accumulation. Matrix metalloproteases (MMPs) and tissue inhibitors of metalloproteases (TIMPs) have been shown to regulate remodeling of the ECM, which indicates that they are important factors in the process of lung fibrosis. Therefore, we evaluated the expression of MMPs and TIMPs in tissues obtained from patients with idiopathic interstitial pneumonia and control tissues. Methods: Thirty-seven patients who were diagnosed with IIP (22: IPF, 13: NSIP, 2: COP) and 5 controls were enrolled in this study. The MMP-2 and -9 activity in lung tissue obtained from these patients was analyzed using gelatin zymography and the levels of TIMP-1 and -2 were measured by western blotting. We also evaluated the expression of MMP-2 and -9, as well as that of TIMP-1 and -2 in lung tissue using immunohistochemistry. Results: The levels of MMP-2 and MMP-9 were significantly increased in patients with IPF compared to those with NSIP and COP. The activities of TIMP-1 and -2 were also higher in patients with IPF than NSIP/COP patients and control subjects. There were no significant differences observed in the activities of MMPs and TIMPs obtained from patients with NSIP/COP and control subjects. The immunohistochemical analysis showed that TIMP-2 and MMP-2 were strongly stained at the fibroblasts of the fibroblastic foci in patients with IPF. Conclusions: These results suggest that over-expression of gelatinases and TIMPs in patients with IPF are important factors in the irreversible fibrosis that is associated with lung parenchyma.

Acute exacerbation of idiopathic pulmonary fibrosis: usual interstitial pneumonitis vs.possible usual interstitial pneumonitis pattern

Background:The prognosis of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is very poor with a high mortality.The aim of this study was to describe the clinical features and survival of patients with AE-IPF with usual pulmonary fibrosis (UIP) and possible UIP (P-UIP) pattern on chest high resolution computed tomography (HRCT).Methods:This retrospective study included 107 patients with AE-IPF admitted to Nanjing Drum Tower Hospital from January 2010 to December 2016.The subjects were divided into UIP (n =86) and P-UIP group (n=21) based on chest HRCT.Continuous variables were analyzed using Student's t test or Mann-Whimey U test.Categorical variables were analyzed using x2 test.Log-rank test was used for the survival analysis.Cox proportional models evaluated the risk factors for AE occurrence and survival.Results:The male,older patients,previous N-acetylcysteine use,elevated white blood cell (WBC) counts,and microbiology infection were more common in the UIP group than the P-UIP group (X2 =13.567,P < 0.001;z =-2.936,P =0.003;X2 =5.901,P =0.015;t =2.048,P =0.043;x2 =10.297,P =0.036,respectively).The percentage of AE with UIP pattern in idiopathic interstitial pneumonia (ⅡP) was significantly higher than P-UIP pattern (X2 =40.011,P < 0.001).Smoking was the risk factor for AE within 6 months after IPF diagnosis in the UIP group.The cumulative proportion survival of 30-days was significantly higher in the UIP group compared with the P-UIP group (x2 =5.489,P =0.019) despite of the similar overall survival in the two groups.Multivariate Cox regression analysis indicated WBC count,partial pressure of oxygen in artery (PaO2)/ffactional concentration of inspired oxygen (FiOz),and computed tomography (CT) score were the independent predictors for survival in the UIP group (hazard ratio [HR]:1.070,95% confidential interval [CI]:1.027-1.114,P=0.001;HR:0.992,95% CI:0.986-0.997,P=0.002;and HR:1.649,95% CI:1.253-2.171,P < 0.001,respectively).Conclusions:AE occurrence of UIP patients in IIP was significantly more than P-UIP cases.The short-term survival was better in the UIP group despite of the similar overall survival in the two groups.WBC count,PaO2/FiO2,and CT score were the independent predictors for survival in UIP subjects.

Interstitial lung disease and diabetes

Diabetes mellitus (DM) is a chronic metabolic disease and its prevalence has beensteadily increasing all over the world. DM and its associated micro andmacrovascular complications result in significant morbidity and mortality. Themicrovascular complications are usually manifested as retinopathy, neuropathy,nephropathy and macrovascular complications generally affect the cardiovascularsystem. In addition to these complications, DM also affects the lungs because of itsrich vascularity and abundance in connective tissue (collagen and elastin). DMhas been found to cause microvascular complications and proliferation ofextracellular connective tissue in the lungs, leading to decline in lung function in arestrictive pattern. Interstitial lung disease (ILD) includes a diverse group ofdisease conditions characterized by different degrees of inflammation and fibrosisin the pulmonary parenchyma. Idiopathic pulmonary fibrosis (IPF) is one of thecommon type of idiopathic interstitial pneumonia with a high mortality rate. IPFis characterized by chronic progressive fibrosis leading to progressive respiratoryfailure. In this review we focus on lung as the target organ in DM and theassociation of DM and ILD with special emphasis on IPF.

Polymyxin B-immobilized fiber columns:A column to breathe new life into the treatment of interstitial lung disease?

Acute exacerbations of idiopathic pulmonary fibrosis(IPF) is a severe respiratory condition with high mortality rate. Direct hemoperfusion with polymyxin B-immobilized fiber columns(PMX-DHP) was originally introduced for the treatment of septic shock. Application of PMX-DHP to the treatment of acute exacerbations of IPF may improve oxygenation and survival of the patients with the disease. In addition to acute exacerbations of IPF, PMXDHP has been applied to acute respiratory failure fromvarious causes; an amyopathic dermatomyositis patient who developed rapidly progressive interstitial lung disease(ILD) with elevated anti-CADM-140/MDA5 autoantibody and a patient with severe amiodarone pulmonary toxicity. It is also demonstrated that PMX-DHP performed on the first day of steroid pulse therapy may improve the prognosis of patients with rapidly progressive ILDs in a case-control setting. PMX treatment decreases not only various circulating molecules but also inflammatory cells, in particular activated monocytes, producing such mediators. Although the incidence of acute exacerbations of IPF is too low for proper randomization, in order to test the effects of PMX-DHP on the disease, a cohort or casecontrol analytic study needs to be conducted, preferably from more than one center or research group.

Genetic characterization of a Chinese family with familial idiopathic pulmonary fibrosis

Background Idiopathic pulmonary fibrosis （IPF） is a chronic inflammatory interstitial lung disease with an unknown cause. Recent studies have shown that genetic factors play an important role in the pathogenesis of IPF. Methods To explore the genetic background of patients with IPF, a candidate gene approach was employed to screen for mutations in seven genes among members with familial IPF in mainland of China. Results Within six of the candidate genes, a total of 31 point mutations were identified. Among the missense mutations, the SFTPA1 exon 6 CAG〉AAG （GIn238Lys） and SFTPB exon 2 CAC〉CCC （His2Pro） mutations caused changes in the physical and chemical properties of amino acids. Each sequence alteration was identified in sporadic IPF patients, control specimens （pneumonia patients and healthy persons）. Genotype frequencies and allele frequencies of codon 238 in exon 6 of SFTPA1 were noted significantly higher in patients with IPF than those in other two control subjects. The computational protein structure prediction by protein homology modeling confirmed differences in three-dimensional structure between mutant SFTPA1 and original SFTPAI. Conclusions Although the functions of the mutant candidate genes vary, these genes may ultimately result in damage to alveolar epithelial cells, initiating the progress of pulmonary fibrosis. In particular, while pathophysiological mechanisms need to be illustrated, the GIn238Lys missense variant of exon 6 in the SFTPA1 may have potential susceptibility in the development of IPF, which was shown in patients with sporadic IPF with a statistically higher frequency.

T淋巴细胞亚群水平对IPF诊断及预后的评估价值

目的分析特发性肺间质纤维化(IPF)患者T淋巴细胞亚群变化及其与预后的关系。方法选取60例IPF患者作为IPF组,根据随访结果分为预后不良组和预后良好组,另选取30例健康体检者作为对照组。比较各组外周血T淋巴细胞亚群水平,分析IPF患者T淋巴细胞亚群水平与高分辨率计算机断层扫描(HRCT)纤维化评分、肺功能及预后的关系。结果治疗前,IPF组患者外周血CD8^(+)水平高于对照组,CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平低于对照组(P<0.05)。IPF组患者入院时CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平与肺功能指标呈正相关,与HRCT评分呈负相关(P<0.05);CD8^(+)水平与肺功能指标呈负相关,与HRCT评分呈正相关(P<0.05)。预后良好组治疗后外周血CD8^(+)水平低于预后不良组,CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平高于预后不良组(P<0.05);IPF患者治疗后外周血CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)ROC曲线下面积分别为0.732、0.744、0.756、0.796(P<0.05)。结论T淋巴细胞亚群水平与IPF患者的预后密切相关,CD8^(+)高水平,CD3^(+)、CD4^(+)低水平可提示其预后不良。

补益肺肾活血方联合西药治疗特发性肺间质纤维化(IPF)随机平行对照研究

[目的]观察补益肺肾活血方联合西药治疗特发性肺间质纤维化(IPF)疗效。[方法]使用随机平行对照方法,将77例门诊患者按随机数字表法分为两组。均按国内常规治疗,并发肺部感染抗生素控制感染,低氧血症吸氧。对照组38例强的松、抗氧化剂。治疗组39例补益肺肾活血方(太子参、麦冬各15g,黄芪40g,山萸肉、浙贝、当归、川芎、赤芍、鳖甲各15g,等),1剂/d,水煎300mL,口服100mL/次,3次/d;西药治疗同对照组。连续治疗12周为1疗程。观测临床症状、生化指标、血气分析、肺功能(用力肺活量-FVC、肺一氧化碳弥散量-DLCO、动脉氧分压-PaO2)、不良反应。治疗1疗程,判定疗效。[结果]治疗组显效3例,有效22例,无效10例,总有效率71.42%;对照组显效1例,有效12例,无效22例,总有效率37.14%;治疗组临床疗效优于对照组(P<0.05)。中医证候疗效治疗组临床控制1例,显效5例,有效21例,无效8例,总有效率77.24%;对照组临床控制1例,显效1例,有效12例,无效21例,总有效率40.00%;治疗组中医证候疗效优于对照组(P<0.05)。治疗组FVC、DLCO、PaO2均明显改善(P<0.05);对照组DLCO明显改善(P<0.05),FVC、PaO2无显著变化(P>0.05);FVC、DLCO改善治疗组优于对照组(P<0.05),PaO2改善两组无显著差异(P>0.05)。[结论]补益肺肾活血方联合西药治疗特发性肺间质纤维化(IPF),疗效满意,无明显副作用,值得推广。

HRCT征象与肺功能检查指标在IPF中的相关性研究

目的 探讨在HRCT各种征象与肺功能检查的指标之间可能存在的相关性。方法 33例临床上怀疑IPF的病人(女性18例,男性15例,年龄范围16-73岁,平均56岁),在连续的时间内接受了HRCT扫描和肺功能检查。对HRCT的图象根据玻璃影、网织、蜂窝、肺气肿、支气管扩张和淋巴结的累及范围进行了评分统计,然后与肺功能能测定的各项指标和功能不全的分级进行Spearman相关性分析和多元回归相关分析。结果 磨玻璃影的范围与动态肺活量的指标FEVI/FVC之间存在负相关,与PEF、MMF之间存在显著负相关(P<0.01),而且与肺功能不全的分级间亦存在相关性。与之不同的是,网织影、蜂窝、支扩的累及范围均与气体弥散指标,尤其是DLco/Va之间存在负相关性(P<0.05),经多元回归分析发现蜂窝的出现对弥散功能影响最大。结论 通过对HRCT征象的分析有助于对肺的功能进行预测,根据磨玻璃影的消长可以估测肺功能不全的轻重,蜂窝的出现则最能表现明弥散功能正在减低。

评价特发性肺纤维化(IPF)中医证素与T淋巴细胞亚群及肿瘤标志物水平的关系

目的探讨特发性肺纤维化(IPF)患者的中医证素与T淋巴细胞亚群及肿瘤标志物水平的关系。方法选取2018年1月—2021年1月河南中医药大学第一附属医院收治的80例特发性肺纤维化(IPF)患者为研究对象,通过对患者的基本资料进行调查和翻阅相关文献,判断患者的中医证素,明确中医证素包括病性证素阴虚、阳虚和病位证素心、肺。选择频率≥10%的证素探讨,其中阴虚22例,阳虚17例,病位证素为心患者25例,肺患者16例。对患者的T淋巴细胞亚群(CD_(3)^(+)、CD_(4)^(+)、CD_(4)^(+)/CD_(8)^(+)T淋巴细胞)、肿瘤标志物[癌胚抗原(CEA)和癌抗原(CA)125、CA153、CA199]进行相关检测并记录。所有患者的基本资料不具有统计学意义(P>0.05)。结果病性证素中,阴虚患者的CD_(3)^(+)、CD_(4)^(+)、CD_(4)^(+)/CD_(8)^(+)T淋巴细胞水平与阳虚患者相差不大,数据差异无统计学意义(P>0.05);阴虚患者与阳虚患者比较,癌胚抗原(CEA)和癌抗原(CA)125、CA153、CA199水平均有所下降,数据差异具有统计学意义(P<0.05)。病位证素中,比较患者的CD_(3)^(+)、CD_(4)^(+)、CD_(4)^(+)/CD_(8)^(+)T淋巴细胞水平,数据差异无统计学意义(P>0.05);比较患者的癌胚抗原(CEA)和癌抗原(CA)125、CA153、CA199水平,数据差异不具有统计学意义(P>0.05)。结论特发性肺纤维化(IPF)患者的中医证素与T淋巴细胞亚群的关系不明显,阳虚证素与患者的肿瘤标志物水平存在一定联系,可以用来判断病情发展情况,表示患者预后不佳。

血清SP-D、SP-A与IPF患者肺功能、血气指标的相关性研究及预后价值探讨

目的研究观察血清肺表面活性蛋白D(SP-D)、肺表面活性蛋白A(SP-A)与特发性间质性肺纤维化(IPF)患者肺功能、血气指标的相关性以及对预后效果的评估价值探讨。方法方便选取该院2016年1月—2017年12月期间收治的50例IPF患者为研究对象,所有患者均采用相同的治疗方案进行药物治疗,分别于治疗前、治疗后1、3、6个月对患者的血清SP-D、SP-A进行检测,并对患者各时间点的肺功能指标:一氧化碳的弥散量(DLCO)、用力肺活量(FVC),氧分压(PaO_2)、肺泡动脉血氧分压差(Pa-aO_2)血气指标进行检测。采用Spearman检验对SP-D、SP-A与肺功能、血气功能指标间的相关性进行分析。结果患者治疗前、治疗后6个月的SP-D、SP-A水平分别为(168.92±27.31)、(137.39±26.64)ng/mL,(21.36±5.84)、(16.21±4.22)ng/mL,且随着治疗时间的延长,SP-D、SP-A水平逐步降低,差异有统计学意义(F=37.361、31.769,P<0.05)。相比与治疗前,治疗后患者的DLCO、FVC、PaO_2均有升高,而Pa-aO_2则有降低,且随着治疗时间延长依次改变,差异有统计学意义(F=28.904、27.024、38.284、31.128,P<0.05)。相关性分析显示,SP-D、SP-A与DLCO、FVC、PaO_2呈负相关性,与Pa-aO_2呈正相关性。结论血清SP-D、SP-A与IPF患者肺功能、血气指标间有明显的相关性,在临床上通过对血清SP-D、SP-A的检测有助于判断和评估患者的预后效果,可为IPF患者诊治提供新的简便方法。

Promising new treatment targets in patients with fibrosing lung disorders

The processes of lung fibrogenesis and fibrotic healing are common to a number of conditions with different etiologies. The lungs are the only affected organ in some cases, whereas in others, several organ systems are involved. Therapeutic options can be discussed from various perspectives. In this review, we address the localization of therapeutic targets with regard to cell compartments, including secreted ligands, cell surface, plasma membrane-cytosol interplay, cytosol and nucleus. Complex approach using stem cell therapy is also discussed. As the prognosis of patients with these disorders remains grim, treatment combinations targeting different molecules within the cell should sometimes be considered. It is reasonable to assume that blocking specific pathways will more likely lead to disease stabilization, while stem cell-based treatments could potentially restore lung architecture. Gene therapy could be a candidate for preventive care in families with proven specific gene polymorphisms and documented familial lung fibrosis. Chronobiology, that takes into account effect of circadian rhythm on cell biology, has demonstrated that timed drug administration can improve treatment outcomes. However, the specificrecommendations for optimal approaches are still under debate. A multifaceted approach to interstitial lung disorders, including cooperation between those doing basic research and clinical doctors as well as tailoring research and treatment strategies toward(until now) unmet medical needs, could improve our understanding of the diseases and, above all, provide benefits for our patients.

LncRNA FEZF1-AS1通过调控EZH2对肺间质细胞增殖、迁移及侵袭的作用

目的研究长链非编码RNA FEZ家族锌指1-反义RNA 1(lncRNA FEZF1-AS1)调控zeste同源物增强子2(EZH2)对肺间质细胞增殖、迁移、侵袭能力及上皮细胞-间质转化(EMT)的影响及其作用机制。方法将人肺腺癌细胞系A549分为对照组(control)和模型组[model,用转化生长因子β1(TGF-β1)20 ng/mL作用48 h,诱导成为肺间质细胞]。用Western blot检测细胞中E-钙黏蛋白(E-cadherin)、N-钙黏蛋白(N-cadherin)及波形蛋白(vimentin)的蛋白表达。RT-qPCR检测细胞中lncRNA FEZF1-AS1和EZH2基因表达。转染组细胞分为转染si NC组、si lncRNA FEZF1-AS1+OE vector组和si lncRNA FEZF1-AS1+OE EZH2组。CCK-8法检测细胞增殖、细胞划痕检测细胞迁移、Transwell小室法检测细胞侵袭;用Western blot检测细胞中E-cadherin、N-cadherin、vimentin及EZH2的蛋白表达,用RNA免疫沉淀(RIP)测定FEZF1-AS1与EZH2的直接结合作用。结果与对照组比较,模型组E-cadherin的蛋白表达水平减少(P<0.05);N-cadherin及vimentin的蛋白表达水平升高(P<0.05);与对照组比较,模型组lncRNA FEZF1-AS1与EZH2基因的表达水平明显升高(P<0.05);与si NC组相比,si lncRNA FEZF1-AS1+OE vector组细胞增殖、迁移、侵袭能力降低,E-cadherin蛋白表达升高,N-cadherin、vimentin、EZH2蛋白表达降低(P<0.05);与si lncRNA FEZF1-AS1+OE vector组比较,si lncRNA FEZF1-AS1+OE EZHZ组细胞增殖、侵袭、迁移能力升高,E-cadherin蛋白表达降低,N-cadherin、vimentin、EZH2蛋白表达升高(P<0.05);RIP实验进一步证实了lncRNA FEZF1-AS1与EZH2具有结合作用。结论LncRNA FEZF1-AS1通过调控EZH2促进肺间质细胞增殖、侵袭、转移和EMT过程。

人工智能在特发性肺纤维化中的研究进展

特发性肺纤维化(IPF)是一种可致死的慢性进行性纤维化间质性肺炎。早期诊断并及时开始抗纤维化治疗是延长IPF病人生存时间的关键。人工智能(AI)技术能够从影像数据中自动学习人眼无法识别的特征,在计算机辅助检测(CAD)系统中的应用可以提供决策支持,有助于提高IPF的诊断准确性并预测疾病进展。就AI的相关概念及其在IPF诊断、疾病进展与预后预测以及药物治疗反应评估中的研究现状予以综述。

LncRNA FEZF1-AS1靶向调控miR-200c-3p对人肺成纤维细胞生物学行为的影响

目的探讨FEZ家族锌指1-反义RNA1(LncRNA FEZF1-AS1)靶向调控miR-200c-3p对人肺成纤维细胞HLF生物学行为的影响。方法采用转化生长因子β1(TGF-β1)诱导HLF向肌成纤维细胞转化,分为空白对照组(Blank组)和造模组(HLF+TGF-β1组),另根据转染质粒不同将细胞分为Blank组、TGF-β1+Si LncRNA FEZF1-AS1 NC组和TGF-β1+Si LncRNA FEZF1-AS1组。采用Western blot法检测α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原蛋白(CollagenⅠ)和波形蛋白(Vimentin)蛋白的表达。采用实时荧光定量PCR(qRT-PCR)检测LncRNA FEZF1-AS1和miR-200c-3p的表达。采用CCK-8法检测细胞增殖,细胞划痕实验检测迁移能力,Transwell实验检测侵袭能力;采用双萤光素酶实验检测FEZF1-AS1与miR-200c-3p的靶向作用关系。结果与Blank组比较,HLF+TGF-β1组α-SMA、CollagenⅠ、Vimentin蛋白表达及LncRNA FEZF1-AS1表达水平升高,miR-200c-3p表达水平降低(P<0.05);与TGF-β1+Si LncRNA FEZF1-AS1 NC组比较,TGF-β1+Si LncRNA FEZF1-AS1组细胞增殖、迁移、侵袭能力下降,LncRNA FEZF1-AS1表达及α-SMA、CollagenⅠ、Vimentin蛋白表达水平降低,miR-200c-3p表达水平升高(P<0.05);FEZF1-AS1与miR-200c-3p基因序列上存在结合位点。结论LncRNA FEZF1-AS1通过抑制miR-200c-3p促进特发性肺间质纤维化的发生、发展。

补阳还五汤治疗特发性肺纤维化的临床疗效分析

目的:探讨补阳还五汤对特发性肺纤维化(IPF)患者的临床疗效。方法:选取2020年6月—2022年6月于荆门市人民医院感染性疾病科就诊的IPF患者120例,随机分为对照组和治疗组各60例,对照组给予醋酸泼尼松片口服,治疗组在常规治疗的基础上给予补阳还五汤口服,治疗6个月后,比较两组患者的血清转化生长因子-β1(TGF-β1)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、肺活量(VC)、肺一氧化碳弥散量(DLCO)和肺总量(TLC),评估临床疗效。结果:治疗组患者TGF-β1(1.03±0.24 pg/mL vs 2.86±0.61 pg/mL)、TNF-α(5.63±1.62 pg/mL vs 9.38±1.55 pg/mL)、IL-6(58.56±3.39 pg/mL vs 64.87±3.19 pg/mL)水平均显著低于对照组(均P<0.001)。治疗6个月后,治疗组患者VC(3.89±0.69 L vs 3.14±0.71 L)、DLCO(61.93±6.59 L vs 55.64±8.30 L)及TLC[4.42(4.27,4.53)L vs 3.84(3.65,3.91)L]均显著高于对照组(均P<0.001)。治疗组患者的临床疗效明显优于对照组(P<0.05)。结论:补阳还五汤治疗IPF,可降低血清TGF-β1、TNF-α、IL-6水平,改善肺功能,临床疗效确切,值得进一步推广应用。

凝血纤溶系统失衡与肺间质纤维化合并呼吸衰竭患者炎性指标相关性分析

目的:探讨凝血纤溶系统失衡与肺间质纤维化(Idiopathic pulmonary fibrosis,IPF)合并呼吸衰竭(Respiratory failure,RF)患者炎性指标相关性。方法:选择我院2020年10月至2023年12月IPF患者98例,依据是否合并RF分为RF组(n=42)与无RF组(n=56)。采用全自动凝血分析仪测定活化部分凝血活酶时间(activated partial thromboplastin time,APTT)、凝血酶时间(thrombin time,TT)、凝血酶原时间(prothrombin time,PT)和纤维蛋白原(fibrinogen,FIB)水平,免疫比浊法测定D-二聚体(D-Dimer,D-D)水平;全自动血细胞分析仪测定中性粒细胞百分比(Neutrophil percentage,NEUT)和白细胞计数(white blood cell count,WBC),酶联免疫吸附法测定C反应蛋白(C-reactive protein,CRP)水平,放射免疫分析法测定降钙素原(Procalcitonin,PCT)水平。比较两组凝血纤溶指标和炎性指标水平变化;采用Pearson分析凝血纤溶指标与炎性指标相关性;分析凝血纤溶指标和炎性指标与IPF合并RF关系。结果:RF组APTT、TT和PT低于无RF组,而FIB和D-D高于无RF组,差异均有统计学意义(P<0.05)。RF组NEUT、WBC、CRP和PCT水平高于无RF组,差异均有统计学意义(P<0.05)。经Pearson分析,APTT、TT和PT与NEUT、WBC、CRP和PCT呈线性负相关,而FIB和D-D与NEUT、WBC、CRP和PCT呈线性正相关(P<0.05)。APTT、TT、PT、FIB、D-D、NEUT、WBC、CRP和PCT为影响IPF合并RF危险因素。结论:IPF合并RF患者存在凝血纤溶系统失衡和炎性反应,且凝血纤溶系统失衡与炎性指标变化密切相关,值得临床借鉴。

无创呼吸机联合吡非尼酮对特发性肺间质纤维化的临床疗效

目的分析无创呼吸机联合吡非尼酮对特发性肺间质纤维化(IPF)的临床疗效。方法选取2019年12月至2020年12月临清市人民医院收治的120例IPF患者作为研究对象,按照随机数字表法分为研究组与对照组,每组60例。对照组采用无创呼吸机治疗,研究组在对照组基础上联用吡非尼酮,比较两组临床疗效、肺功能指标[第1秒用力呼气容积(FEV1)及第1秒用力呼气容积占预计值的百分比(FEV1/FVC%)]、血流动力学指标[平均动脉压(MAP)、心率(HR)]及血清炎症因子[肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)]水平。结果研究组治疗总有效率为96.67%,高于对照组的85.00%,差异有统计学意义(P<0.05);治疗后,两组FEV1、FEV1/FVC%均高于治疗前,且研究组高于对照组,差异有统计学意义(P<0.05);治疗后,两组MAP、HR均低于治疗前,且研究组低于对照组,差异有统计学意义(P<0.05);治疗后,两组TNF-ɑ、IL-6水平均低于治疗前,且研究组低于对照组,差异有统计学意义(P<0.05)。结论无创呼吸机联合吡非尼酮治疗IPF的疗效显著,能有效缓解患者心肺功能指标,改善血流动力学指标和炎症因子水平,值得临床推广应用。