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.

TNF-α Up-regulates Matrix Metalloproteinase-9 Expression and Activity in Alveolar Macrophages from Patients with Chronic Obstructive Pulmonary Disease

To study the effects of tumor necrosis factor （TNF）-α on matrix metalloproteinase （MMP）-9 expression and activity in alveolar macrophages （AM） and to investigate the role of NF-κB in the induction, AM were collected from bronchoalveolar lavage fluid （BALF） of healthy subjects and patients with chronic obstructive pulmonary disease （COPD）. MMP-9 expression and activity were detected by semi-quantitative reverse transcription-polymerase chain reaction （RT-PCR）, Western blotting and zymography. NF-κB activity was detected by electrophoretic mobility shift assay （EMSA）. MMP-9 expression and activity induced by TNF-α in AM from healthy subjects or patients with COPD were significantly increased in a dose-dependent manner （P〈0.05）. NF-κB activity induced by TNF-α was significantly increased in AM from patients with COPD, and pyrrolidine dithiocarbamate （PDTC） and N-acetyl-L-cysteine （NAC） significantly inhibited the activation of NF-κB induced by TNF-α （P〈0.05）. The presents study suggested that the expression and activity of MMP-9 from AM can be induced by TNF-α, and TNF-α/NF-κB signal pathway may play an important role in the induction.

Anti-inflammatory role of microRNA let-7c in LPS treated alveolar macrophages by targeting STAT3

Objective:To explore the expression of microRNA(miRNA) let-7c and its function in chronic obstructive pulmonary disease(COPD) and alveolar macrophage cells.Methods:Real time PCR was performed to detect the expression of miRNA let-7c in the lung tissue of COPD patients and COPD model in mice.MiRNA let-7c was overexpresscd in alveolar macrophages isolated from mice and its effect was measured by the production of pro-inflammation cytokines and the protein level of signal transducer and activator of transcription 3(STAT3) as well as phosphorylation level of STAT3 after LPS stimulation.Luciferase assay was used to detect the binding of miRNA let-7c and 3'UTR of STAT3.Results:MiRNA let-7c expression was significantly lower in patients with COPD compared with control group,and the similar result was found in COPD mice and LPS stimulated alveolar macrophages.Overexpression of miRNA lct-7c in alveolar macrophages inhibited LPS-induced increasing of tumor necrosis factor alpha,interleukin-6 and interleukin-1β.Luciferase assay showed STAT3 was a targeting of miRNA lct-7c in alveolar macrophages.Conclusions:MiRNA lct-7c low expression in COPD can regulate inflammatory responses by targeting STAT3 in alveolar macrophage,which may provide a new target for COPD treatment strategies.

Induction of matrix metalloproteinase-9 in alveolar macrophages by TNF-α through NF-κB signal pathway

Objective： To explore the effect of tumor necrosis factor （TNF）-α on matrix metalloproteinase-9 （MMP-9） expression and activity in alveolar macrophages （AM） from patients with chronic obstructive pulmonary disease （COPD） and study its associated signal pathway. Methods： AM were collected from bronchoalveolar lavage fluid in patients with COPD. The AM were incubated for 1.5 h with pyrrolidine dithiocarbamate（PDTC） at concentrations from 0 μmol/L to 50μmol/L and then stimulated for 24 h by TNF-α at 10 ng/ml. MMP-9 expression and activity were respectively detected by semi-quantitative reverse transcription-polymerase chain reaction （RT-PCR）, Western blotting and Zymography. NF-κB activity was investigated by electrophoretic mobility shift assay （EMSA）. Results： Both the mRNA and protein levels of MMP-9 induced by TNF-α in AM were significantly elevated in a dose dependent manner （ P 〈 0.05）. The level of MMP-9 activity was also correspondingly significantly elevated in the induction （ P 〈 0.05）, which was possibly related with the over-expression of MMP-9. NF-κB activity was significantly increased when AM were stimulated by 10 ng/mL TNF-α （ P 〈 0.05）. The expression of MMP-9 induced by TNF-α could be significantly inhibited by PDTC （P 〈 0.05 ）. Conclusion： The expression and activity of MMP-9 from AM could be induced by TNF-α, and NF-κB signal pathway played an important role in the induction.

Surfactant protein D inhibits lipid-laden foamy macrophages and lung inflammation in chronic obstructive pulmonary disease

Increased levels of surfactant protein D (SP-D) and lipid-laden foamy macrophages (FMs) are frequently found under oxidative stress conditions and/or in patients with chronic obstructive pulmonary disease (COPD) who are also chronically exposed to cigarette smoke (CS). However, the roles and molecular mechanisms of SP-D and FMs in COPD have not yet been determined. In this study, increased levels of SP-D were found in the bronchoalveolar lavage fluid (BALF) and sera of ozone- and CS-exposed mice. Furthermore, SP-D-knockout mice showed increased lipid-laden FMs and airway inflammation caused by ozone and CS exposure, similar to that exhibited by our study cohort of chronic smokers and COPD patients. We also showed that an exogenous recombinant fragment of human SP-D (rfhSP-D) prevented the formation of oxidized low-density lipoprotein (oxLDL)-induced FMs in vitro and reversed the airway inflammation and emphysematous changes caused by oxidative stress and CS exposure in vivo. SP-D upregulated bone marrow-derived macrophage (BMDM) expression of genes involved in countering the oxidative stress and lipid metabolism perturbations induced by CS and oxLDL. Our study demonstrates the crucial roles of SP-D in the lipid homeostasis of dysfunctional alveolar macrophages caused by ozone and CS exposure in experimental mouse emphysema, which may provide a novel opportunity for the clinical application of SP-D in patients with COPD.

Reducing systemic absorption and macrophages clearance of genistein by lipid-coated nanocrystals for pulmonary delivery

Pulmonary delivery is an effective drug delivery strategy for the treatment of local respiratory diseases.However,the rapid systemic absorption through the lung due to the thin barrier and persistent lung clearances influence the drug retention in the lung.In this study,we designed a lipid-coated genistein nanocrystals(Lipo-NCs)formulation to achieve enhanced efficiency of local pulmonary delivery.The LipoNCs were fabricated by modifying genistein nanocrystals(NCs)with phospholipid membrane through thin film hydration following the homogenization method.The prepared Lipo-NCs exhibited a decreased drug release rate compared with the naked NCs.Our results demonstrated that intracellular uptake and transcellular transport of NCs by the Calu-3 epithelial layer were reduced after lipid coating.Furthermore,the macrophages clearance was also impeded by this Lipo-NCs formulation.In vivo lung retention and distribution revealed that more genistein was retained in the lung after intratracheal administration of Lipo-NCs.The pharmacokinetic study displayed that the AUC((0-t))values of Lipo-NCs were 1.59-fold lesser than those of the NCs group,indicating a reduced systemic absorption.In conclusion,this research indicated that Lipo-NCs could be a suitable formulation for reducing systemic absorption and macrophages clearance,and thus enhancing drug concentration in lung by pulmonary delivery.

Neotuberostemonine and tuberostemonine ameliorate pulmonary fibrosis through suppressing TGF-β and SDF-1 secreted by macrophages and fibroblasts via the PI3K-dependent AKT and ERKpathways

Activated fibroblasts and M2-polarized macrophages may contribute to the progression of pulmonary fibrosis by forming a positive feedback loop.This study was aimed to investigate whether fibroblasts and macrophages form this loop by secreting SDF-1 and TGF-β and the impacts of neotuberostemonine(NTS)and tuberostemonine(TS).Mice were intratracheally injected with 3 U·kg^(-1)bleomycin and orally administered with 30 mg·kg^(-1)NTS or TS.Primary pulmonary fibroblasts(PFBs)and MH-S cells(alveolar macrophages)were used in vitro.The animal experiments showed that NTS and TS improved fibrosis related indicators,inhibited fibroblast activation and macrophage M2 polarization,and reduced the levels of TGF-β and SDF-1 in alveolar lavage fluid.Cell experiments showed that TGF-β1 may activated fibroblasts into myofibroblasts secreting SDF-1 by activating the PI3K/AKT/HIF-1αand PI3K/PAK/RAF/ERK/HIF-1αpathways.It was also found for the first time that SDF-1 was able to directly polarize macrophages into M2 phenotype secreting TGF-β through the same pathways as mentioned above.Moreover,the results of the cell coculture confirmed that fibroblasts and macrophages actually developed a feedback loop to promote fibrosis,and the secretion of TGF-β and SDF-1 was crucial for maintaining this loop.NTS and TS may disturb this loop through inhibiting both the PI3K/AKT/HIF-1αand PI3K/PAK/RAF/ERK/HIF-1α pathways to improve pulmonary fibrosis.NTS and TS are stereoisomeric alkaloids with pyrrole[1,2-ajazapine skeleton,and their effect on improving pulmonary fibrosis may be largely attributed to their parent nucleus.Moreover,this study found that inhibition of both the AKT and ERK pathways is essential for maximizing the improvement of pulmonary fibrosis.

Increased activity of protein kinase C in alveolar macrophages in idiopathic pulmonary fibrosis

Objective To investigate the changes on protein kinase C (PKC) activity of alveolar macrophages (AMs) in patients with idiopathic pulmonary fibrosis (IPF) Methods The PKC activity of AM in 9 healthy volunteers and 15 patients with IPF was investigated by measuring the radioactivity Results The total, cytosolic and membrane PKC activity of AM in bronchoalveolar lavage fluid (BALF) from patients with IPF were higher than those from control group ( P <0 01, P <0 05 and P <0 05, respectively) The total and the membrane associated PKC activity had a positive correlation with the number of cells in BALF ( r =0 8135, P <0 01 and r =0 5917, P <0 05), respectively Conclusion As a bypass of transmembrane signal transduction, PKC was suggested to be involved in the origination and development of IPF

Monocyte and macrophage function in respiratory viral infections

Pulmonary macrophages,such as tissue-resident alveolar and interstitial macrophages and recruited monocyte-derived macrophages,are the major macrophages present in the lungs during homeostasis and diseased conditions.While tissue-resident macrophages act as sentinels of the alveolar space and play an important role in maintaining homeostasis and immune regulation,recruited macrophages accumulate in the respiratory tract after acute viral infections.Despite sharing similar anatomical niches,these macrophages are distinct in terms of their origins,surface marker expression,and transcriptional profiles,which impart macrophages with distinguished characteristics in physi-ological and pathophysiological conditions.In this review,we summarize the current view on these macrophage populations,their shared functions,and what makes them distinct from each other in the context of homeostasis andrespiratoryviral infections.

The Differences of Interstitial Lung Diseases in High-Resolution Computerized Tomography and Pulmonary Function Test among Different Connective Tissue Diseases, and the Correlated Factors

Objective. To study the difference of interstitial lung diseases (ILDs) in high-resolution computerized tomography and pulmonary function test among different connective tissue diseases (CTDs). Methods. 209 patients with different CTDs were recruited and underwent lung HRCT and PFT. Eerythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum ferritin (SF), anti-SSA, and so on were tested. Based on HRCT, a patient was classified into ILD group (CTD+ILD) or non-ILD group (CTD-ILD). HRCT, PFT, and laboratory markers were compared according to CTDs and CTD-associated ILDs. Results. The incidences of ILD were 79.6%, 82.0%, 89.7%, and 97.1% respectively for Rheumatoid arthritis (RA), primary Sjogren’s symptom (pSS), dermatomyositis/polymyositis (DM/PM), and systemic sclerosis (SSc) groups. RA and pSS patients exhibited more nodules, patching, ground-glass opacity, and cord shadow foci in HRCT, DM/PM and SSc patients exhibited more reticular opacity and honeycombing foci. RA and pSS patients exhibited more obstructive ventilatory disorder, small airway dysfunction and emphysema in PFT, and DM/PM and SSc patients exhibited more restrictive ventilatory disorder, mixed ventilatory disorder. ESR, CRP and SF were significantly higher in total CTD+ILD group than in total CTD-ILD group (P = 0.047, 0.006, 0.004, respectively), and higher in different CTD+ ILD groups than in comparable CTD-ILD groups (P = 0.049, 0.048, and 0.023, pSS+ILD, SSc+ILD and RA+ILD compared to pSS-ILD, SSc-ILD and RA-ILD, respectively for ESR, CRP, SF). The positive rate of anti-SSA was significantly higher in DM/PM+ILD group than in DM/PM-ILD group (P = 0.025). Conclusions. The manifestations and incidences of ILDs differ among different CTDs in HRCT and PFT, and inflammation and anti-SSA are positively correlated with ILDs in different CTDs, which provide important evidences for judging disease condition and prognosis.

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.

巨噬细胞向肌成纤维细胞转化促进LPS诱导的急性肺损伤模型小鼠肺纤维化

目的探讨巨噬细胞向肌成纤维细胞转化(MMT)在脂多糖(LPS)诱导的急性肺损伤小鼠肺纤维化过程中的作用。方法将21只小鼠分为7组:对照组、不同时间点LPS诱导小鼠早期肺纤维化(LPS-PF)模型组和不同时间点氯磷酸二钠脂质体(CL-LIP)干预组(n=3)。用HE、Masson染色评估各组肺纤维化程度;用免疫荧光检测MMT过程中CD68和α-平滑肌动蛋白(α-SMA)共标记阳性细胞数量。骨髓来源巨噬细胞(BMDMs)分为对照(Ctrl)组和转化生长因子-β1(TGF-β1)刺激组(n=3);用RT-qPCR检测各组α-SMA、纤连蛋白(FN)、人I型胶原蛋白(Col1)表达水平。用Western blot检测各组间α-SMA以及Smad同源物3(Smad3)、磷酸化的Smad3(p-Smad3)蛋白表达量。结果LPS-PF模型小鼠肺组织第7天Ashcroft评分较对照(Ctrl)组显著增高(P<0.01);但在CL-LIP组中肺纤维化程度较LPS-PF组明显减轻(P<0.05)。肺组织免疫荧光染色发现,CL-LIP组CD68α-SMA共标记阳性细胞数较LPS-PF组对应时间点明显减少(P<0.01)。体外实验中,TGF-β1刺激组48 h、96 h后α-SMA、FN、Col1较对应时间点表达量明显增加(P<0.01)。检测体内、体外实验中Smad3、p-Smad3的蛋白表达量,发现LPS-PF组(第7天、第10天)和TGF-β1刺激组(48 h和96 h)均较各自对照(Ctrl)组明显增加(P<0.01)。结论MMT具有促进LPS诱导模型小鼠肺纤维化的作用,其转化过程可能经Smad3调节。

藏红花素缓解野百合碱诱导动脉型肺动脉高压大鼠右心室损伤的机制研究

目的:观察藏红花素能否缓解野百合碱(MCT)诱导动脉型肺动脉高压(PAH)大鼠的右心室损伤,并探讨其可能的作用机制。方法:40只雄性SD大鼠随机分为normal组、PAH组、crocin组及sildenafil组,每组10只。PAH组、crocin组及sildenafil组大鼠皮下注射MCT(50 mg/kg)建立PAH模型。自注射MCT之日起,crocin组大鼠给予藏红花素(200 mg/kg)、sildenafil组大鼠给予西地那非(30 mg/kg)、PAH组及normal组大鼠给予等量生理盐水每日1次灌胃。4周后,测定各组大鼠右心室收缩压(RVSP)、平均肺动脉压(mPAP)、右心室肥大指数(RVHI)和右心室质量指数(RVMI);组织染色观察右心室病理变化;检测右心室炎性因子(IL-1β、IL-6、TNF-α)、p38 MAPK/NF-κB炎性通路、CCL2、CCR2及巨噬细胞标记物CD68的表达。结果:与PAH组相比,crocin组及sildenafil组大鼠RVSP、mPAP、RVHI和RVMI降低(P<0.05);右心室炎症细胞浸润和胶原纤维增生不明显;p38 MAPK/NF-κB通路和炎性因子(IL-1β、IL-6和TNF-α)的表达下调(P<0.05);CCL2/CCR2通路表达及CD68+巨噬细胞浸润减少(均P<0.05)。结论:藏红花素可显著缓解MCT诱导PAH大鼠的右心室损伤,其作用与本实验剂量下西地那非的作用相当;藏红花素的部分保护机制可能与其对炎症的调节作用有关。

CTD-ILD合并肺部感染患者肺部微生物菌群特点及对肺纤维化的影响

目的探讨结缔组织病相关间质性肺疾病(CTD-ILD)合并肺部感染患者肺部微生物菌群特点及对肺纤维化的影响。方法选取2021年2月至2022年5月在医院治疗的45例CTD-ILD合并肺部感染患者作为观察组,同时选取45例CTD-ILD未合并肺部感染患者作为对照组,比较两组肺功能、高分辨CT(HRCT)肺纤维化评分,同时分析观察组病原菌分布情况。结果观察组用力肺活量占预计值百分比(FVC%pred)、第1秒用力呼气容积占预计值百分比(FEV 1%pred)、一氧化碳弥散量占预计值百分比(DLCO%pred)、用力肺活量(FVC)、最大呼气流量(MEF)和残气容积(RV)低于对照组(P<0.05);观察组HRCT影像学斑片状、支气管扩张比率高于对照组(P<0.05),CT纤维化评分高于对照组(P<0.05)。观察组病原菌分布:细菌分布中以肺炎克雷伯菌、铜绿假单胞菌为主,分别占24.44%和15.56%,病毒检出巨细胞病毒、人类疱疹病毒,分别占11.11%和6.67%,真菌检出白念珠菌,占11.11%。观察组年龄≥60岁患者CT纤维化评分高于年龄<60岁患者(P<0.05)。结论CTD-ILD合并肺部感染患者以细菌感染为主;相比较未合并肺部感染患者,合并肺部感染患者肺纤维化较重。

黏蛋白1与呼吸系统疾病关系的研究进展

慢性黏液高分泌导致的气道炎症可能会逐渐进展并影响患者的肺功能。黏液蛋白是黏液层的关键成分,其中黏蛋白1是一种重要的膜结合型黏蛋白,目前的研究聚焦于评估黏蛋白1在肺纤维化、肺癌和间质性肺疾病等肺部疾病中的临床应用,尤其是作为诊断、预测进展和评估治疗效果的生物标志物。因此,深入了解黏蛋白1在肺部疾病中的生物学机制和作用方式,特别是与疾病发展和进展的关联,探索黏蛋白1在肺部疾病早期诊断和预后评估中的预测价值,将为肺部疾病的诊断和治疗提供新的理论依据。

MS19通过抑制IRF5表达调控巨噬细胞极化减轻CTD-ILD肺部炎症的作用研究

目的 探讨MS19通过靶向干扰素调节因子5(IRF5)对结缔组织疾病相关肺间质病变(CTD-ILD)小鼠模型肺部炎症的治疗作用及其相关机制。方法 动物实验:构建CTD-ILD小鼠模型,予以MS19干预,研究MS19对CTD-ILD小鼠肺部炎症的影响。细胞实验:对RAW264.7细胞进行OE-IRF5转染,然后予以MS19干预,研究MS19对IRF5调控的巨噬细胞M1型极化及炎症反应的影响。结果 动物实验:CTD-ILD小鼠出现明显的肺部炎症,小鼠支气管肺泡灌洗液(BALF)中IRF5的表达增高、巨噬细胞M1型极化增加及促炎因子(TNF-α、IL-6和IL-1β)的表达升高;而MS19干预后,CTD-ILD小鼠的肺部炎症减轻,BALF中IRF5表达降低、巨噬细胞M1型极化减少及促炎因子表达下降。细胞实验:脂多糖诱导巨噬细胞M1型极化、促炎因子表达增加;转染OE-IRF5后,巨噬细胞M1型极化增加、促炎因子表达增加;MS19干预后,巨噬细胞M1型极化减少、促炎因子表达减少。结论 MS19通过靶向抑制IRF5调控巨噬细胞极化及炎症反应,从而改善CTD-ILD的肺部炎症,为防治CTD-ILD提供潜在靶点和候选药物。

血清KL-6水平对利妥昔单抗相关间质性肺疾病的诊断意义

目的研究血清涎液化糖链抗原-6(KL-6)水平对利妥昔单抗相关间质性肺疾病(RTX-ILD)的诊断价值。方法选取航天中心医院呼吸与危重症医学科治疗的120例非霍奇金淋巴瘤(NHL)应用利妥昔单抗(RTX)化疗的患者,入组患者于第1次化疗前记录临床资料包括血清KL-6水平等基线值,于第4次化疗前测定血清KL-6水平以及氧分压(PO_(2))等;根据化疗后是否合并ILD,分为RTX-ILD组(51例),不合并ILD组(69例);另外,RTX-ILD组根据临床影像以及症状再分为4级。分析血清KL-6水平与PO_(2)、病情严重程度的相关性。绘制受试者工作曲线(ROC曲线),计算血清KL-6水平诊断RTX-ILD的临界值。结果RTX-ILD组的血清KL-6水平(1201±728U/mL)明显高于不合并ILD组(189±110U/mL),差异具有统计学意义(t=7.125,P<0.05);RTX-ILD组患者第4次治疗前,血清KL-6水平604±321U/mL,差异有统计学意义(χ^(2)=3.56,P<0.05);在临床诊断分级中,G1、G2、G3、G4级分组间的血清KL-6水平分别为989±589U/mL、1175±699U/mL、1204±836U/mL、1332±994U/mL,差异有统计学意义(χ^(2)=4.34,P<0.05)。相关性分析结果显示,血清KL-6水平与动脉血气分析PO_(2)呈负相关(r=-0.827,P<0.05)。血清KL-6检测的临界值为520U/mL时,其诊断RTX-ILD的灵敏度和特异性分别为83.2%(95%CI 70.3%~90.1%)和77.0%(95%CI 73.4%~84.3%),ROC曲线下面积为0.798。结论血清KL-6水平在NHL应用RTX化疗的患者中随着罹患RTX-ILD风险增高而升高,是潜在预测RTX-ILD指标,血清KL-6水平测定有利于RTX-ILD的诊断及病情的评估。

基于CT征象和血清巨噬细胞集落刺激因子、β-连环蛋白构建的联合模型对孤立性肺结节的评估价值

目的探讨基于CT征象和血清巨噬细胞集落刺激因子(M-CSF)、β-连环蛋白(β-Catenin)构建的联合模型对孤立性肺结节的评估价值。方法选取2020年2月至2023年2月萍乡市人民医院病理结果显示孤立性肺结节的105例患者作为研究对象,以孤立性肺结节性质为结局指标,软件计算建模组所需样本量为75例,故随机抽取75例作为建模组、其余30例作为验证组,分析建模组孤立性肺结节不同性质患者一般资料、CT征象、生化指标,多因素logistic回归分析法筛选影响孤立性肺结节性质的独立影响因子,并建立预测模型。用验证组临床资料进行验证并将验证组临床资料代入预测模型,根据预测概率绘制ROC曲线评估该预测模型的效能。结果建模组75例病例中,良性肺结节43例(57.33%)、恶性肺结节32例(42.67)。单因素分析结果显示,良性、恶性肺结节患者毛刺征、分叶征、血管集束征、胸膜凹陷征、磨玻璃密度、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、癌胚抗原(CEA)、神经特异性烯醇化酶(NSE)、M-CSF、β-Catenin水平与建模组孤立性肺结节性质有关,差异有统计学意义(P<0.05)。多因素logistic回归分析显示:毛刺征(β=1.572,OR=1.612,95%CI=1.475~2.159)、分叶征(β=1.484,OR=1.650,95%CI=1.408~2.184)、血管集束征(β=1.292,OR=1.674,95%CI=1.466~2.198)、磨玻璃密度(β=1.307,OR=1.785,95%CI=1.501~2.263)、CEA(β=0.915,OR=1.797,95%CI=1.505~2.199)、NSE(β=0.920,OR=1.824,95%CI=1.618~2.218)、M-CSF(β=0.859,OR=1.765,95%CI=1.506~2.301)、β-Catenin(β=0.867,OR=1.806,95%CI=1.542~2.325)是影响建模组孤立性肺结节性质的独立危险因素(P<0.05),据此建立的联合模型ROC曲线结果显示:该模型评估孤立性肺结节良恶性的灵敏度为90.50%、特异度为75.26%、AUC为0.880(95%CI=0.802~0.935)、阳性似然比为4.05、阴性似然比为0.12、阳性预测值为82.80%、阴性预测值为89.90%。结论毛刺征、分叶征、血管集束征、磨玻璃密度及CEA、NSE、M-CSF、β-Catenin水平升高是影响孤立性肺结节良恶性的独立影响因素,据此构建的联合模型评估孤立性肺结节良恶性的效能较高。

转染miR-223模拟物的巨噬细胞结核分枝杆菌清除能力、凋亡、炎症反应变化及miR-223与NLRP3靶向关系

目的 观察肺结核患者血清微小RNA-223(miR-223)水平变化,以及转染miR-223模拟物的巨噬细胞结核分枝杆菌(MTB)H37Rv清除能力、凋亡、炎症反应变化,并分析miR-223与NLRP3靶向关系。方法 选取37例份活动性肺结核患者血清标本(肺结核组)和同期40例健康体检者血清标本(健康组),采用RT-PCR法检测两组血清标本中miR-223。体外培养人单核细胞株THP-1,经佛波脂刺激24 h后分化为巨噬细胞,将巨噬细胞随机分为健康组、MTB组、MTB+mimics-NC组、MTB+miR-223 mimics组,健康组细胞常规培养,MTB组、MTB+mimics-NC组、MTB+miR-223 mimics组均用MTB标准株H37Rv感染巨噬细胞,感染后MTB+mimics-NC组和MTB+miR-223 mimics组应用脂质体转染法分别将mimics-NC、miR-223 mimics转染至细胞中,采用RT-PCR法检测各组细胞miR-223及NLRP3、TNF-α、IFN-γ mRNA,流式细胞术测算各组细胞凋亡率,菌落形成单位(CFU)计数法检测各组H37Rv细菌负荷量。取对数生长期THP-1细胞,随机分为miR-223 mimics+NLRP3-WT组、mimics-NC+NLRP3-WT组、miR-223mimics+NLRP3-MUT组、mimics-NC+NLRP3-MUT组,用Lipofectamine 2000按照试剂盒说明书操作分别将miR-223mimics和NLRP3-WT、mimics-NC和NLRP3-WT、miR-223 mimics和NLRP3-MUT、mimics-NC和NLRP3-MUT共转染至各组细胞,转染后24 h检测各组细胞的相对荧光素酶活性,双荧光素酶报告基因实验验证miR-223与NLRP3是否存在靶向关系。结果 与健康组比较,肺结核组血清miR-223表达降低(P<0.05)。与健康组比较,MTB组miR-223表达、细胞凋亡率降低,NLRP3、TNF-α、IFN-γ mRNA表达及H37Rv细菌负荷量升高(P均<0.05);与MTB+mimics-NC组比较,MTB+miR-223 mimics组miR-223表达、细胞凋亡率升高,NLRP3、TNF-α、IFN-γ mRNA表达及H37Rv细菌负荷量降低(P均<0.05)。双荧光素酶报告基因实验显示,NLRP3是miR-223的靶向基因。结论 肺结核患者血清miR-223表达降低,转染miR-223模拟物能够促进巨噬细胞凋亡,增强MTB感染的巨噬细胞的除菌能力,减轻炎症反应,其机制可能与靶向调控NLRP3有关。

进行性纤维化间质性肺病患者规范化肺康复训练实施方案的构建

目的 基于循证医学,构建一套适用于进行性纤维化间质性肺病患者的规范化肺康复训练方案,丰富肺康复指导的系统教育方案内涵,为临床康复护理提供科学指导。方法 计算机检索中国WanFang数据库、中国知网数据库(CNKI)、维普数据库(VIP)、中国生物医学文献数据库(CBM)、PubMed、Embase、Cochrane Library、Web of Science数据库文献及指南网站,以循证医学为指导,通过文献回顾分析,采用《临床指南研究与评价系统》(Appraisal of Guidelines for Research and Evaluation,AGREEⅡ)评价指南质量及澳大利亚JBI(Joanna Briggs Institute)循证卫生保健中心开发的文献质量评价工具对随机对照试验、系统评价、类实验文献进行质量评价,对纳入的文献进行全文阅读及等级划分,以汇总最佳证据,拟定进行性纤维化间质性肺病患者肺康复训练方案初稿,最后结合专家会议和专家咨询结果,对方案初稿进行可用性评鉴,最终修订完善方案。结果 经文献质量评价及筛选后,共纳入30篇文献,其中指南与专家共识3篇,随机对照试验文献16篇,系统评价文献6篇,类实验文献5篇。方案内容包括训练评估、呼吸训练、运动训练、健康教育、社会心理干预、营养支持6个一级指标。结论 该研究构建的方案结果可靠,其规范性、科学性和安全性高,能够为进行性纤维化间质性肺病患者临床康复护理工作提供参考。