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.

Visual Analysis of Knowledge Map of Traditional Chinese Medicine in Prevention and Treatment of Pulmonary Interstitial Fibrosis Based on CiteSpace

Objective: To analyze the relevant research literature on the prevention and treatment of pulmonary interstitial fibrosis with traditional Chinese medicine (TCM), understand the current research status, hot spots and future development trend in this field, and provide basis and feasible suggestions for further research in this field. Methods: The journal literatures related to the prevention and treatment of pulmonary interstitial fibrosis with TCM in recent 20 years in CNKI database were searched and passed through CiteSpace 5.8.R3 generates the knowledge map of relevant literature authors, document issuing institutions and keywords, and makes visual analysis. Results: A total of 1,576 documents were included, and the annual number of documents showed a fluctuating upward trend, forming a relatively stable research team represented by authors such as LYU Xiaodong, PANG Lijian and LIU Chuang;According to the atlas of document issuing institutions, Shandong University of Traditional Chinese Medicine and its affiliated hospitals ranked first in the number of documents issued, and the cooperation between institutions is dominated by the University of traditional Chinese medicine and its affiliated hospitals;Keyword cluster analysis shows that a large number of studies have been carried out in the field of etiology and pathogenesis, TCM compound, clinic and experiment. Conclusion: The research on the prevention and treatment of pulmonary interstitial fibrosis with TCM has a high degree of attention, but the cooperation network between the research authors and institutions needs to be strengthened. The research on the pathogenesis and improving the quality of life of patients is the trend of development in the future.

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.

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.

Sleep disordered breathing in interstitial lung disease: A review

Patients with interstitial lung disease commonly exhibit abnormal sleep architecture and increased sleep fragmentation on polysomnography. Fatigue is a frequent complaint, and it is likely that poor sleep quality is a significant contributor. A number of studies have shown that sleep disordered breathing is prevalent in this population, particularly in the idiopathic pulmonary fibrosis subgroup. The factors that predispose these patients to obstructive sleep apnoea are not well understood, however it is believed that reduced caudal traction on the upper airway can enhance collapsibility. Ventilatory control system instability may also be an important factor, particularly in those with increased chemo-responsiveness, and in hypoxic conditions. Transient, repetitive nocturnal oxygen desaturation is frequently observed in interstitial lung disease, both with and without associated obstructive apnoeas. There is increasing evidence that sleep-desaturation is associated with increased mortality, and may be important in the pathogenesis of pulmonary hypertension in this population.

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.

Acute exacerbation of interstitial lung disease in the intensive care unit:Principles of diagnostic evaluation and management

Interstitial lung disease(ILD)is typically managed on an outpatient basis.Critical care physicians manage patients with ILD in the setting of an acute exacerbation(ILD flare)causing severe hypoxia.The principles of management of acute exacerbation of ILD are different from those used to manage patients with acute respiratory distress syndrome from sepsis,etc.Selected patients may be candidates for aggressive measures like extracorporeal membrane oxygenation and lung transplantation,while almost all patients will benefit from early palliative care.This review focused on the types of ILD,diagnosis,and management pathways for this challenging condition.

“瘀毒”理论指导下不同肺系疾病诊疗思路

基于长期以来的临床实践经验和大量临床、基础研究,团队创新性提出“肺生血”“肺为血脏”理论,既拓展了既往教科书中的认识,又扩充了中医基础理论的内容;并以此为基础,系统提出“瘀毒”为肺系疾病病机变化的主要特点,构建“瘀毒”理论指导下的理法方药完备的肺系疾病证治体系,将“瘀毒”理论应用到支气管哮喘、慢性阻塞性肺疾病、肺间质纤维化、肺癌等肺系疾病的防治中。支气管哮喘、慢性阻塞性肺疾病急性发作期以标实为主,瘀毒兼痰,选用活血兼化痰之品;肺间质纤维化,瘀毒入络,选用活血作用较强且兼具通络作用的虫类药;肺癌,瘀毒兼癌毒,选用具有活血解毒和抗肿瘤作用的药物。临床治疗肺系疾病,需在考虑不同疾病特点的前提下,重视祛瘀解毒之法的运用。

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.

IPF合并肺气肿与未合并肺气肿患者的临床特点、肺功能、影像学及生活质量比较

目的探讨特发性肺间质纤维化(IPF)合并肺气肿和单纯肺间质纤维化患者临床特点、肺功能、影像学习和生活质量的差异。方法分析2014年2月至2015年8月接受治疗的70例IPF合并肺气肿(IPF合并肺气肿组)和80例单纯IPF(单纯IPF组)患者的临床资料。观察2组患者炎性因子、肺功能、影像学指标和生活质量的差异。结果 PF合并肺气肿组患者的IL-8、IL-17、hs-CRP和TNF-α水平均高于单纯IPF组(t=-51.543、-32.180、-11.545、-6.997,P<0.01);IPF合并肺气肿组患者FVC、FEV1、FEV1/FVC、MMEF和PEF水平均低于单纯IPF组(t=3.747、10.759、9.443、7.562、21.072,P<0.001);IPF合并肺气肿组患者的Sp O2水平低于单纯IPF组(P<0.01),PETCO2水平高于单纯IPF组(P<0.01);单纯IPF组患者除肢体疼痛外,生活质量各维度得分均高于IPF合并肺气肿组(P<0.01)。结论 IPF合并肺气肿患者的肺功能和生活质量均较单纯IPF患者差,且有明显的影像学特征。

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。

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。

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。

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。

慢性阻塞性肺疾病合并肺间质纤维化的相关危险因素分析

目的探讨慢性阻塞性肺疾病合并肺间质纤维化的相关危险因素。方法选择莆田学院附属医院2021年1月—2023年2月收治的92例慢性阻塞性肺疾病患者作为研究对象。其中合并肺间质纤维化36例设为研究组,未合并肺间质纤维化56例设为对照组,总结分析慢性阻塞性肺疾病合并肺间质纤维化的相关危险因素。结果治疗后,对照组的肺功能评价指标第1秒用力呼气容积(forced expiratory volume in one second,FEV1)、用力肺活量(forced vital capacity,FVC)及FEV1/FVC分别为(2.98±0.65)L、(3.79±0.82)L、(71.32±3.52)%,高于研究组的(2.12±0.61)L、(3.13±0.74)L、(63.76±3.26)%,差异均有统计学意义(P<0.05)。单因素分析显示,2组患者的年龄、肺功能、反流性食管炎、吸烟史差异有统计学意义(P<0.05)。多因素logistic回归分析显示,年龄、肺功能、反流性食管炎、吸烟史是慢性阻塞性肺疾病合并肺间质纤维化的危险因素(OR=4.862、4.745、4.424、5.516,P<0.001)。结论年龄、肺功能、反流性食管炎、吸烟史是慢性阻塞性肺疾病合并肺间质纤维化的危险因素,应强化对高龄患者的管理,积极改善患者肺功能,做好反流性食管炎治疗,有效降低合并肺间质纤维化的风险,提高患者生命健康质量,且为临床慢性阻塞性肺疾病合并肺间质纤维化防治标准制定提供借鉴内容。

间歇性呼吸康复训练对间质性肺疾病稳定期病人疲乏程度、运动能力及肺纤维化进程的影响

目的:研究间歇性呼吸康复训练对间质性肺疾病稳定期病人疲乏程度、运动能力及肺纤维化进程的影响。方法:选取2021年1月—2023年1月医院收治的78例间质性肺疾病稳定期病人为研究对象,按照随机数字表法将其分为对照组和观察组,每组39例。对照组给予常规肺康复,观察组采用间歇性呼吸康复训练,比较干预后两组疲乏程度[多维度疲乏量表(MFI-20)]、运动能力[6 min内步行距离(6 MWD)、呼吸困难量表(mMRC)]及肺纤维化进程。结果:干预后,观察组层粘连蛋白(LN)、透明质酸酶(HA)、细胞间黏附分子-1(ICAM-1)水平均低于对照组,血红素加氧酶-1(HO-1)水平高于对照组(P<0.05);观察组6 MWD长于对照组,mMRC评分低于对照组(P<0.05);观察组MFI-20评分低于对照组(P<0.05)。结论:间歇性呼吸康复训练能够有效缓解间质性肺疾病稳定期病人疲乏程度,提高病人运动能力,延缓肺纤维化进程。

人参皂苷Rb1通过调控Wnt3/β-catenin通路对结缔组织并发间质性肺炎大鼠肺纤维化的影响

目的探究人参皂苷Rb1通过调控Wnt3/β-catenin通路对改善结缔组织并发间质性肺炎大鼠肺纤维化的作用机制。方法85只大鼠随机分为假手术组、模型组、人参皂苷Rb1组、Wnt3/β-catenin激活剂(HLY78)组及人参皂苷Rb1+HLY78组,每组17只;除假手术组外的4组大鼠均采用博来霉素法诱导建立大鼠间质性肺炎模型,各组随机选择2只大鼠评价造模是否成功,采用BUXCO动物肺功能分析系统和ELISA法检测大鼠肺功能、血清炎症因子及纤维化因子水平;HE及Masson染色观察肺病理损伤形态;免疫荧光共定位法测β-catenin与肺成纤维细胞(标记抗体-FSP-1)及肺间充质干细胞(标记抗体-Nanog)共表达变化;Western blot法测Wnt3/β-catenint通路及下游纤维化相关蛋白表达。结果与假手术组相比,模型组大鼠呼吸困难、死亡、肺功能受损、纤维化加重等症状严重,β-catenin^(+)FSP-1^(+)及β-catenin^(+)Nanog^(+)表达升高,Wnt3/β-catenin通路活性升高(P<0.05);人参皂苷Rb1可缓解大鼠上述症状,并抑制Wnt3/β-catenin活性、降低β-catenin^(+)FSP-1^(+)及β-catenin^(+)Nanog^(+)表达(P<0.05);Wnt3/β-catenin激活剂-HLY78可减弱人参皂苷Rb1的上述作用(P<0.05)。结论人参皂苷Rb1可能通过抑制Wnt3/β-catenin通路在肺成纤维细胞及间充质干细胞中表达,阻断肌成纤维细胞转化,而延缓大鼠肺纤维化进程。

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.