Nrp1 Negatively Regulates PI3K/AKT Pathway to Inhibit the Activation of Lung Fibroblasts and Its Role in Mouse Pulmonary Fibrosis

doi:10.12114/j.issn.1007-9572.2025.0204

Chinese General Practice ›› 2026, Vol. 29 ›› Issue (26): 3788-3797.DOI: 10.12114/j.issn.1007-9572.2025.0204

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Nrp1 Negatively Regulates PI3K/AKT Pathway to Inhibit the Activation of Lung Fibroblasts and Its Role in Mouse Pulmonary Fibrosis

1. Ningxia Key Laboratory of Clinical and Pathogenic Microorganisms, Institute of Medical Science, General Hospital of Ningxia Medical University, Yinchuan 750004, China
2. The First Clinical Medical College of Ningxia Medical University, Yinchuan 750004, China
3. Department of Respiratory and Critical Care Medicine, General Hospital of Ningxia Medical University, Yinchuan 750004, China

Received:2025-04-10 Revised:2025-07-31 Published:2026-09-15 Online:2026-08-11
Contact: CHEN Juan
About author:
CHENG Guocang and JIA Yuanyuan are co-first authors

神经纤毛蛋白1负调控磷脂酰肌醇3-激酶/蛋白激酶B通路抑制肺成纤维细胞活化及其在小鼠肺纤维化中的作用研究

1．750004　宁夏回族自治区银川市，宁夏医科大学总医院医学科学研究院临床病原微生物重点实验室
2．750004　宁夏回族自治区银川市，宁夏医科大学第一临床医学院
3．750004　宁夏回族自治区银川市，宁夏医科大学总医院呼吸与危重症医学科

通讯作者: 陈娟
作者简介:
程国仓和贾元元为共同第一作者
作者贡献：
程国仓负责动物实验，数据采集，绘制图表和论文起草；贾元元负责细胞和分子生物学实验、数据分析和最终版本修订；赵停婷、齐瑞鑫、念苗苗负责临床血样收集和处理；陈娟负责文章的质量控制与审查，对文章整体负责。
基金资助:
国家自然科学基金资助项目(82460200); 宁夏自然科学基金资助项目(2022AAC03550); 中央引导地方科技发展专项(2024FRD05046); 宁夏重点研发计划项目(2023BEG02021)

Abstract

Abstract:

Background

Idiopathic pulmonary fibrosis (IPF) has a complex pathogenesis, limited treatment options and a poor prognosis. Therefore, it is crucial to identify the safe and effective therapeutic targets.

Objective

To investigate the regulatory effect of Nrp1 on the activation of mouse pulmonary fibroblasts (MPFs) through PI3K/AKT signaling pathway and the therapeutic effect and safety of recombinant Nrp1 protein on pulmonary fibrosis (PF) in mice.

Methods

GSE150910, GSE218997, GSE173523, GSE47460, and GSE32537 were downloaded from the GEO database to analyze the expression of Nrp1 in lung tissues of PF mouse models and IPF patients, as well as the correlation between Nrp1 expression and pulmonary function parameters in IPF patients. A total of 45 IPF patients diagnosed in the Department of Respiratory and Critical Care Medicine and 29 healthy controls who underwent physical examinations in the health management center in General Hospital of Ningxia Medical University from 2022 to 2024 were selected. Cell-free RNA (cfRNA) sequencing was used to analyze the expression levels of Nrp1 in the plasma of IPF patients and healthy controls and its diagnostic efficacy. MPFs were divided into the control group, TGF-β1 group, Nrp1 overexpression group and TGF-β1+Nrp1 overexpression group. TGF-β1 was used to induce the activation of MPFs, and the effects of Nrp1 overexpression on the PI3K/AKT pathway and the expression of α-SMA, Vim and Fn were detected. Thirty male C57BL/6J mice were randomly divided into the control group, BLM group and BLM+Nrp1 group, with 10 mice in each group. After establishing the mouse PF model, the BLM+Nrp1 group was intraperitoneally injected with 100 μg·kg^-1·d^-1 of recombinant Nrp1 protein for 20 consecutive days. HE and Masson staining were used to observe the pathological changes of mouse lung tissues, and liver and kidney function indicators were evaluated. Western blotting and immunohistochemistry were used to detect the expression of α-SMA, Vim and Fn in lung tissues. ELISA was used to measure the levels of Nrp1 in plasma and BALF.

Results

Compared with normal lung tissues, The expression of Nrp1 was decreased in the lung tissues of PF mouse and IPF patients (P<0.05), and the expression of Nrp1 was positively correlated with FEV₁%pred, FVC%pred and DLCO%pred. The mRNA expression of Nrp1 in plasma of IPF patients was significantly lower than that of healthy controls (P<0.05), and the area under the receiver operating characteristic curve of plasma Nrp1 for diagnosing IPF was 0.754 (95%CI=0.634-0.874). Compared with the TGF-β1 group, the ratios of p-PI3K/PI3K and p-AKT/AKT in the TGF-β1+Nrp1 overexpression group were decreased, and the expression of α-SMA, Vim and Fn was decreased (P<0.05). After intraperitoneal injection of recombinant Nrp1 protein, the pathological features of PF in mice were improved. There were no statistically significant differences in the levels of ALT, AST, ALP, BUN and CREA in plasma among the control group, BLM group and BLM+Nrp1 group (P>0.05). Compared with the BLM group, the expression of α-SMA and Fn in the lung tissues of the BLM + Nrp1 group was decreased, and the levels of Nrp1 in plasma and BALF were increased (P<0.05).

Conclusion

The expression of Nrp1 is decreased in the lung tissues, plasma and BALF of IPF patients. Nrp1 inhibits the activation of mouse pulmonary fibroblasts by negatively regulating the PI3K/AKT signaling pathway. Intraperitoneal injection of recombinant Nrp1 protein can alleviate pulmonary fibrosis in mice and exhibits systemic safety.

Key words: Pulmonary fibrosis, Neuropilin-1, Fibroblast activation, Recombinant Nrp1 protein

摘要：

背景

特发性肺纤维化（IPF）发病机制复杂、治疗手段有限、预后差，因此寻找安全有效的治疗靶点至关重要。

目的

探究神经纤毛蛋白1（Nrp1）通过磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/AKT）信号对小鼠肺成纤维细胞（MPFs）活化的调控作用，以及重组蛋白Nrp1对小鼠肺纤维化（PF）的治疗作用及安全性。

方法

从基因表达数据库（GEO数据库）下载数据集GSE150910、GSE218997、GSE173523、GSE47460和GSE32537，分析PF小鼠模型和IPF患者肺组织中Nrp1表达以及Nrp1与IPF患者肺功能指标的相关性。选取2022—2024年在宁夏医科大学总医院呼吸与危重症医学科确诊的IPF患者45例，以及同期在本院健康管理中心体检的健康对照者29例，采用游离RNA（cfRNA）测序分析IPF患者和健康对照者血浆Nrp1表达水平及其诊断效能。将MPFs分为对照组、转化生长因子β1（TGF-β1）组、Nrp1过表达组和TGF-β1+Nrp1过表达组，TGF-β1诱导MPFs活化，过表达Nrp1检测其对PI3K/AKT通路和α-平滑肌肌动蛋白(α-SMA）、波形蛋白Vimentin（Vim）和纤连蛋白Fibronection（Fn）表达的影响。将30只雄性C57BL/6J小鼠随机分为对照组、博来霉素（BLM）组、BLM+Nrp1组，每组10只。构建小鼠PF模型后，BLM+Nrp1组连续20 d腹腔注射100 μg·kg^-1·d^-1的重组蛋白Nrp1。采用HE和Masson染色观察小鼠肺组织病理变化，评估小鼠肝肾功能指标，采用Western blotting和免疫组化检测肺组织中α-SMA、Vim和Fn表达，采用酶联免疫吸附试验（ELISA）测定血浆和支气管肺泡灌洗液（BALF）中Nrp1水平。

结果

数据集分析结果显示，与正常肺组织相比，PF小鼠和IPF患者肺组织中Nrp1表达降低（P<0.05），Nrp1表达与第1秒用力呼气量占预计值百分比（FEV₁%pred）、用力肺活量占预计值百分比（FVC%pred）、一氧化碳弥散量占预计值百分比（DLCO%pred）呈正相关。IPF患者血浆Nrp1 mRNA表达水平低于健康对照者（P<0.05），血浆Nrp1诊断IPF的受试者工作特征曲线下面积为0.754（95%CI=0.634~0.874）。与TGF-β1组相比，TGF-β1+Nrp1过表达组中p-PI3K/PI3K、p-AKT/AKT表达降低，α-SMA、Vim和Fn表达降低（P<0.05）。腹腔注射重组蛋白Nrp1后，PF小鼠肺部病理特征改善，对照组、BLM组、BLM+Nrp1组血浆丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、碱性磷酸酶（ALP）、血尿素氮（BUN）和肌酐（CREA）水平比较，差异均无统计学意义（P>0.05）。与BLM组比较，BLM+Nrp1组小鼠肺组织中α-SMA和Fn表达降低，血浆和BALF中Nrp1水平升高（P<0.05）。

结论

IPF患者肺组织、血浆及BALF中Nrp1表达降低。Nrp1通过负向调控PI3K/AKT信号通路抑制小鼠肺成纤维细胞活化。腹腔注射重组Nrp1可以缓解小鼠肺纤维化，具有系统安全性。

关键词: 肺纤维化, 神经纤毛蛋白1, 肺成纤维细胞活化, 重组蛋白Nrp1

CLC Number:

R 563.13

CHENG Guocang,JIA Yuanyuan,ZHAO Tingting, et al. Nrp1 Negatively Regulates PI3K/AKT Pathway to Inhibit the Activation of Lung Fibroblasts and Its Role in Mouse Pulmonary Fibrosis[J]. Chinese General Practice, 2026, 29(26): 3788-3797. DOI: 10.12114/j.issn.1007-9572.2025.0204.
程国仓,贾元元,赵停婷等. 神经纤毛蛋白1负调控磷脂酰肌醇3-激酶/蛋白激酶B通路抑制肺成纤维细胞活化及其在小鼠肺纤维化中的作用研究[J]. 中国全科医学, 2026, 29(26): 3788-3797. DOI: 10.12114/j.issn.1007-9572.2025.0204.

Figures/Tables 15

References 25

[1]	Wan R Y, Wang L, Duan Y D, et al. ADRB2 inhibition combined with antioxidant treatment alleviates lung fibrosis by attenuating TGFβ/SMAD signaling in lung fibroblasts[J]. Cell Death Discov, 2023, 9(1): 407.
[2]	Zabihi M, Shahriari Felordi M, Lingampally A, et al. Understanding myofibroblast origin in the fibrotic lung[J]. Chin Med J Pulm Crit Care Med, 2024, 2(3): 142-150. DOI: 10.1016/j.pccm.2024.08.003.
[3]	Vásquez-Pacheco E, Marega M, Lingampally A, et al. Highlighting fibroblast plasticity in lung fibrosis: the WI-38 cell line as a model for investigating the myofibroblast and lipofibroblast switch[J]. Theranostics, 2024, 14(9): 3603-3622. DOI: 10.7150/thno.93519.
[4]	Glass D S, Grossfeld D, Renna H A, et al. Idiopathic pulmonary fibrosis: current and future treatment[J]. Clin Respir J, 2022, 16(2): 84-96. DOI: 10.1111/crj.13466.
[5]	Ma J, Li G, Wang H, et al. Comprehensive review of potential drugs with anti-pulmonary fibrosis properties[J]. Biomed Pharmacother, 2024, 173: 116282. DOI: 10.1016/j.biopha.2024.116282.
[6]	Barratt S L, Mulholland S, Al Jbour K, et al. South-west of England's experience of the safety and tolerability pirfenidone and nintedanib for the treatment of idiopathic pulmonary fibrosis(IPF)[J]. Front Pharmacol, 2018, 9: 1480. DOI: 10.3389/fphar.2018.01480.
[7]	Gulati S, Luckhardt T R. Updated evaluation of the safety, efficacy and tolerability of pirfenidone in the treatment of idiopathic pulmonary fibrosis[J]. Drug Healthc Patient Saf, 2020, 12: 85-94.
[8]	Broz M, Kolarič A, Jukič M, et al. Neuropilin(NRPs)related pathological conditions and their modulators[J]. Int J Mol Sci, 2022, 23(15): 8402. DOI: 10.3390/ijms23158402.
[9]	Valdembri D, Regano D, Maione F, et al. Class 3 semaphorins in cardiovascular development[J]. Cell Adh Migr, 2016, 10(6): 641-651.
[10]	Kazemi M, Carrer A, Moimas S, et al. VEGF121 and VEGF165 differentially promote vessel maturation and tumor growth in mice and humans[J]. Cancer Gene Ther, 2016, 23(5): 125-132.
[11]	Zhao J Q, Bai J, Peng F L, et al. USP9X-mediated NRP1 deubiquitination promotes liver fibrosis by activating hepatic stellate cells[J]. Cell Death Dis, 2023, 14(1): 40.
[12]	Yi J X, Gao H, Wei X F, et al. The transcription factor GATA3 positively regulates NRP1 to promote radiation-induced pulmonary fibrosis[J]. Int J Biol Macromol, 2024, 262(Pt 2): 130052.
[13]	佘炜, 魏江, 董丹丹, 等. NRP1调控M2型巨噬细胞极化介导电离辐射肺纤维化的作用研究[J]. 中国免疫学杂志, 2023, 39(2): 252-256. DOI: 10.3969/j.issn.1000-484X.2023.02.005.
[14]	Yombo D J K, Ghandikota S, Vemulapalli C P, et al. SEMA3B inhibits TGFβ-induced extracellular matrix protein production and its reduced levels are associated with a decline in lung function in IPF[J]. Am J Physiol Cell Physiol, 2024, 326(6): C1659-C1668.
[15]	Zhang J J, Qiu J X, Zhou W Y, et al. Neuropilin-1 mediates lung tissue-specific control of ILC2 function in type 2 immunity[J]. Nat Immunol, 2022, 23(2): 237-250.
[16]	Evyapan G, Senturk N C, Celik I S. Correction: ornidazole inhibits the angiogenesis and migration abilities of non-small cell lung cancer(NSCLC)via downregulation of VEGFA/VEGFR2/NRP-1 and PI3K/AKT/mTOR pathways[J]. Cell Biochem Biophys, 2025, 83(1): 1325. DOI: 10.1007/s12013-024-01501-8.
[17]	Wang L, Feng Y M, Xie X Y, et al. Neuropilin-1 aggravates liver cirrhosis by promoting angiogenesis via VEGFR2-dependent PI3K/Akt pathway in hepatic sinusoidal endothelial cells[J]. EBioMedicine, 2019, 43: 525-536. DOI: 10.1016/j.ebiom.2019.04.050.
[18]	Raghu G, Remy-Jardin M, Myers J L, et al. Diagnosis of idiopathic pulmonary fibrosis. an official ATS/ERS/JRS/ALAT clinical practice guideline[J]. Am J Respir Crit Care Med, 2018, 198(5): e44-e68.
[19]	Farkas L, Horowitz J C, Mora A L. How a fibroblast ages: a role for bone morphogenetic protein 4 in protecting lung fibroblasts from senescence in pulmonary fibrosis[J]. Eur Respir J, 2022, 60(6): 2201702. DOI: 10.1183/13993003.01702-2022.
[20]	Ng B, Dong J R, D'Agostino G, et al. Interleukin-11 is a therapeutic target in idiopathic pulmonary fibrosis[J]. Sci Transl Med, 2019, 11(511): eaaw1237. DOI: 10.1126/scitranslmed.aaw1237.
[21]	梅倩茹. 抑制剂XI-011靶向MDM4治疗特发性肺纤维化[D]. 武汉: 华中科技大学, 2024.
[22]	董卓. NRP1基因特异性敲除对放射性肺纤维化进程的影响及其作用机制[D]. 长春: 吉林大学, 2020.
[23]	Fu J W, He J Y, Zhang L M, et al. Comprehensive analysis and immunohistochemistry localization of NRP1 expression in pancancer and normal individual tissues in relation to SARS-CoV-2 susceptibility[J]. Exp Ther Med, 2023, 27(2): 52.
[24]	Wang H T, Sun K, Peng H, et al. Emerging roles of noncoding RNAs in idiopathic pulmonary fibrosis[J]. Cell Death Discov, 2024, 10(1): 443. DOI: 10.1038/s41420-024-02170-5.
[25]	Liu C, Somasundaram A, Manne S, et al. Neuropilin-1 is a T cell memory checkpoint limiting long-term antitumor immunity[J]. Nat Immunol, 2020, 21(9): 1010-1021.

基因名称	基因ID	引物序列	产物长度（bp）
Nrp1	18186	F：CTCTCTCCACAAGGTTCATCAG	100
		R：GTAGGTGCTTCCACTTCACA
Fn	14268	F：GACTCATGGTGGCCACTAAATA	115
		R：CTTCTTGGAGGGCTAACATTCT
α-SMA	11475	F：TCAGGGAGTAATGGTTGGAATG	112
		R：GGTGATGATGCCGTGTTCTA
Vim	22352	F：CCCTGAACCTGAGAGAAACTAAC	93
		R：CTCTGGTCTCAACCGTCTTAATC
GAPDH	14433	F：GGTTGTCTCCTGCGACTTCA	183
		R：TGGTCCAGGGTTTCTTACTCC
β-actin	11461	F：TCATCCATGGCGAACTGGTG	92
		R：AAGGAAGGCTGGAAAAGAGC

基因名称	基因ID	引物序列	产物长度（bp）
Nrp1	18186	F：CTCTCTCCACAAGGTTCATCAG	100
		R：GTAGGTGCTTCCACTTCACA
Fn	14268	F：GACTCATGGTGGCCACTAAATA	115
		R：CTTCTTGGAGGGCTAACATTCT
α-SMA	11475	F：TCAGGGAGTAATGGTTGGAATG	112
		R：GGTGATGATGCCGTGTTCTA
Vim	22352	F：CCCTGAACCTGAGAGAAACTAAC	93
		R：CTCTGGTCTCAACCGTCTTAATC
GAPDH	14433	F：GGTTGTCTCCTGCGACTTCA	183
		R：TGGTCCAGGGTTTCTTACTCC
β-actin	11461	F：TCATCCATGGCGAACTGGTG	92
		R：AAGGAAGGCTGGAAAAGAGC

组别	例数	性别（男/女）	年龄[M（P₂₅，P₇₅），岁]	BMI（±s，kg/m²）	FVC（±s，L）	FVC%pred[M（P₂₅，P₇₅），%]	TLC（±s，L）	TLC%pred（±s，%）	DLCO%pred[M（P₂₅，P₇₅），%]
健康对照者	29	18/11	63（61，67）	25.1±3.1	3.60±0.70	111.50（88.45，120.25）	5.18±0.86	92.48±3.43	92.50（84.80，104.75）
特发性肺纤维化患者	45	27/18	66（62，70）	25.1±2.5	2.80±0.68	79.50（69.00，90.00）	4.48±0.86	71.81±11.70	53.00（44.00，64.00）
检验统计量值		0.032^a	539.000^b	0.072	3.737	86.000^b	1.536	3.481	8.000^b
P值		0.859	0.208	0.943	<0.001	<0.001	0.133	0.001	<0.001

组别	例数	性别（男/女）	年龄[M（P₂₅，P₇₅），岁]	BMI（±s，kg/m²）	FVC（±s，L）	FVC%pred[M（P₂₅，P₇₅），%]	TLC（±s，L）	TLC%pred（±s，%）	DLCO%pred[M（P₂₅，P₇₅），%]
健康对照者	29	18/11	63（61，67）	25.1±3.1	3.60±0.70	111.50（88.45，120.25）	5.18±0.86	92.48±3.43	92.50（84.80，104.75）
特发性肺纤维化患者	45	27/18	66（62，70）	25.1±2.5	2.80±0.68	79.50（69.00，90.00）	4.48±0.86	71.81±11.70	53.00（44.00，64.00）
检验统计量值		0.032^a	539.000^b	0.072	3.737	86.000^b	1.536	3.481	8.000^b
P值		0.859	0.208	0.943	<0.001	<0.001	0.133	0.001	<0.001

组别	α-SMA	Vim	Fn	Nrp1
对照组	1.000±0.016	1.000±0.065	1.000±0.020	1.000±0.050
TGF-β1组	1.378±0.105^a	1.003±0.026	2.508±0.061^a	0.294±0.010^a
Nrp1过表达组	0.801±0.067^a	0.844±0.041^a	0.592±0.009^a	2.132±0.015^a
TGF-β1+Nrp1过表达组	0.703±0.021^b	0.866±0.037^b	0.779±0.067^b	0.612±0.053^b
F值	65.63	10.88	1 057.00	1 360.00
P值	<0.000 1	0.003 4	<0.000 1	<0.000 1

Nrp1 Negatively Regulates PI3K/AKT Pathway to Inhibit the Activation of Lung Fibroblasts and Its Role in Mouse Pulmonary Fibrosis

神经纤毛蛋白1负调控磷脂酰肌醇3-激酶/蛋白激酶B通路抑制肺成纤维细胞活化及其在小鼠肺纤维化中的作用研究

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组别	α-SMA	Vim	Fn	Nrp1
对照组	1.000±0.035	1.000±0.019	1.000±0.022	1.000±0.030
TGF-β1组	1.396±0.014^a	1.101±0.023	1.546±0.039^a	0.744±0.042^a
Nrp1过表达组	0.136±0.029^a	0.553±0.035^a	0.185±0.006^a	1.368±0.023^a
TGF-β1+Nrp1过表达组	0.349±0.032^b	0.668±0.037^b	0.268±0.006^b	1.394±0.026^b
F值	1 225.00	236.70	2 364.00	300.60
P值	<0.000 1	<0.000 1	<0.000 1	<0.000 1

组别	p-PI3K/PI3K	p-AKT/AKT
对照组	1.000±0.009	1.000±0.006
TGF-β1组	2.900±0.171^a	1.429±0.060^a
Nrp1过表达组	0.687±0.121^a	0.935±0.023
TGF-β1+Nrp1过表达组	0.820±0.013^b	0.915±0.036^b
F值	428.60	128.90
P值	<0.000 1	<0.000 1

组别	ALT（±s，U/L）	AST（±s，U/L）	ALP（±s，U/L）	BUN[M（P₂₅，P₇₅），mmol/L]	CREA（±s，μmol/L）	BUN/CREA（±s）
对照组	33.350±5.639	93.150±7.490	81.500±34.857	9.000（8.475，9.800）	13.925±1.992	0.677±0.132
BLM组	23.275±5.010	105.820±19.032	89.750±42.680	7.800（7.450，7.825）	14.075±2.824	0.553±0.148
BLM+Nrp1组	39.400±25.549	105.650±14.389	96.250±25.171	8.450（7.500，9.250）	13.475±0.801	0.619±0.133
F（Z）值	1.122	1.014	0.179	2.100^a	0.093	0.808
P值	0.367	0.401	0.839	0.085	0.912	0.476

组别	α-SMA	Vim	Fn	Nrp1
对照组	1.000±0.181	1.000±0.250	1.000±0.597	1.000±0.209
BLM组	1.875±0.268^a	2.602±0.051^a	12.650±0.893^a	0.363±0.067^a
BLM+Nrp1组	1.404±0.440	2.317±0.215	6.365±3.043^b	0.564±0.379
F值	5.371	435.5	29.22	5.572
P值	0.046	<0.0001	0.008	0.043

组别	只数	BALF	血浆
对照组	4	482.588±41.030	442.518±34.359
BLM组	4	292.586±38.597^a	205.975±97.804^a
BLM+Nrp1组	4	591.949±79.132^b	501.745±147.847^b
F值		9.450	27.37
P值		0.0061	0.0001

[1]	MAO Ruixiao, FENG Zhenzhen, LIU Wenrui, WANG Jiajia, LI Jiansheng. Analysis of the Temporal and Spatial Evolution of TCM Syndromes in Idiopathic Pulmonary Fibrosis in the Past 30 Years [J]. Chinese General Practice, 2026, 29(19): 2678-2687.
[2]	ZHANG Mingyue, HOU Yan. Research Progress of Exhaled Nitric Oxide and Alveolar Nitric Oxide in Interstitial Lung Diseases [J]. Chinese General Practice, 2026, 29(18): 2571-2576.
[3]	YANG Qifen, ZHAO Huiliang, GUO Yongsheng, QU Jinglian. The Impact of the Jagged1/Notch1 Signalling Pathway on Endothelial-mesenchymal Transition in Idiopathic Pulmonary Fibrosis [J]. Chinese General Practice, 2025, 28(25): 3151-3160.
[4]	HUANG Lihui, SHU Juan, TAO Huihui, BAO Hairong. Progress in Treatment of Post Inflammatory Pulmonary Fibrosis Induced by SARS-CoV-2 Infection [J]. Chinese General Practice, 2024, 27(32): 4085-4092.
[5]	XU Lili, HONG Yunzhe, LI Zhihui, YU Ningxia, DI Jiaqi, YANG Shuguang, LIN Qingqing, YU Xueqing. Prognostic Biomarkers in Idiopathic Pulmonary Fibrosis: a Recent Review [J]. Chinese General Practice, 2023, 26(03): 372-379.
[6]	CAI Bo，CHEN Xianqiu，YANG Wenlan，YANG Guanghong，HUANG Jin，QUAN Hua，FENG Yonghong. Comparison of the Predictive Value of GAP Staging and CPI for Risk of Death in Patients with Idiopathic Pulmonary Fibrosis　 [J]. Chinese General Practice, 2021, 24(35): 4485-4491.
[7]	. Misdiagnosis and Diagnosis Analysis of Three Cases of Pediatric Idiopathic Pulmonary Hemosiderosis　 [J]. Chinese General Practice, 2019, 22(14): 1751-1754.
[8]	LIU Rui，HE Jia，LIANG Ziyang，LIU Xiufang，HOU Tibao，WU Juanjuan. Effects of Maimendong Decoction on the Expression Levels of TGF-β1，MMP-9 and TIMP-1 in Lung Tissue of a Rat Model of Bleomycin-induced Pulmonary Fibrosis　 [J]. Chinese General Practice, 2018, 21(29): 3590-3596.
[9]	PENG Shou-chun, LI Xue-ren. Relevance Analysis of Changes in Clinical Indicators and Pulmonary Physiological Parameters and Prognosis of Idiopathic Pulmonary Fibrosis [J]. Chinese General Practice, 2016, 19(35): 4338-4345.