Molecular mechanisms and cellular process in signal transduction pathway related to air pollutants in obstructive lung diseases:A mini-review

Exposure to air pollutants such as PM_(10),PM_(2.5),PM_(0.1),O_(3),CO,NO2,and SO_(2),and biological pollutants are important factors causing the evolution and furtherance of obstructive lung diseases(OLD),including asthma and chronic obstructive pulmonary disease(COPD).Asthma is the most frequent chronic inflammatory airway disease,characterized by breathlessness,wheezing,chest tightness,and cough,together with the presence of exaggerated expiratory airflow fluctuation that varies over time.COPD is a heterogeneous lung condition characterized by chronic respiratory symptoms such as dyspnea,cough,expectoration,and/or exacerbations due to abnormalities of the airways and/or alveoli that cause persistent,often progressive,airflow obstruction.Understanding the molecular mechanisms and cellular processes based on the development of OLD on exposure to air pollutants will provide insights into the solution of pathogenesis,prevention,and treatment of these conditions.The molecular mechanisms and cellular process involved in signal transduction pathway plays a role in the binding of extracellular signaling molecules and ligands to receptors placed on the cell surface or on the inner side cell that trigger inflammation that occurs,especially when something important enters the cell to bring into a cascade response.This binding then alters the cell metabolism,shape,and gene expression in the airway.This review aimed to reveal the effect of air pollutants on the molecular mechanisms and cellular processes involved in the signal transduction pathways in OLD.

Research progress of red blood cell distribution width in diagnosis and treatment of lung diseases and prognosis

Lung disease is the disease of the lung itself or lung manifestations of other diseases,including COPD,PTE,CAP,etc.In recent years,the incidence rate has been increased year after year.Many of these diseases have hidden onset and complicated causes.Therefore,accurate diagnosis and treatment are very important.Studies have shown that RDW is closely linked to the diagnosis and treatment of lung diseases.This article analyzes the research on RDW and lung diseases at home and abroad,and briefly summarizes the diagnosis,severity and clinical prognosis of lung diseases by RDW,hoping to provide useful clues and reliable basis for clinical workers,to provide assistance for further application research of RDW in lung diseases.

Acupoint selection rules for acupoint application in lung diseases in the post-epidemic era

Objective:To summarize the rules of acupoint selection of acupoint application to prevent and treat lung diseases under the background the post-epidemic era using data-mining technology.Method:The CNKI,Wanfang database,and VIP database were searched for clinical study articles on lung diseases treated by acupoint application published in the past 5 years.Data-eligible papers were extracted to establish a database of acupoint application for lung disease using Microsoft Excel 2019,with the goal of analyzing the frequency of acupoints,acupoint-meridian association,acupoint-location association,specific acupoint frequency,and cluster analysis.Association rules,consisting of acupoints with an application frequency of≥10,were devised by the Apriori algorithm to explore the correlation between acupoint groups and to analyze the rules of the compatibility of acupoint prescriptions.Results:A total of 229 eligible papers met our inclusion criteria.Forty-seven acupoints were applied,for a total frequency of acupoints of 1,035 times.Among these,acupoints for lung diseases were primarily distributed in the back-and-waist and chest-and-abdomen areas.From the analysis of the association rules,we obtained four groups of acupoint association rules based on acupoint clusters with a frequency≥10 and found that Feishu(BL 13),Tiantu(CV 22),Dazhui(GV 14),Dingchuan(EX-B1),and Danzhong(CV 17)constitute the core acupoints of prescriptions for clinical acupoint application to prevent and treat lung diseases.Conclusion:It is clearly shown that the core acupoints are relatively concentrated and that the selected acupoints were mainly locally selected,which could be a matching reference for the long-term prevention and treatment of lung diseases,including COVID-19.

Non-Invasive Early Diagnosis of Obstructive Lung Diseases Leveraging Machine Learning Algorithms

Lungs are a vital human body organ,and different Obstructive Lung Diseases(OLD)such as asthma,bronchitis,or lung cancer are caused by shortcomings within the lungs.Therefore,early diagnosis of OLD is crucial for such patients suffering from OLD since,after early diagnosis,breathing exercises and medical precautions can effectively improve their health state.A secure non-invasive early diagnosis of OLD is a primordial need,and in this context,digital image processing supported by Artificial Intelligence(AI)techniques is reliable and widely used in the medical field,especially for improving early disease diagnosis.Hence,this article presents an AIbased non-invasive and secured diagnosis for OLD using physiological and iris features.This research work implements different machine-learning-based techniques which classify various subjects,which are healthy and effective patients.The iris features include gray-level run-length matrix-based features,gray-level co-occurrence matrix,and statistical features.These features are extracted from iris images.Additionally,ten different classifiers and voting techniques,including hard and soft voting,are implemented and tested,and their performances are evaluated using several parameters,which are precision,accuracy,specificity,F-score,and sensitivity.Based on the statistical analysis,it is concluded that the proposed approach offers promising techniques for the non-invasive early diagnosis of OLD with an accuracy of 97.6%.

Primary biliary cholangitis presenting with granulomatous lung disease misdiagnosed as lung cancer:A case report

BACKGROUND There are few cases of pulmonary granulomatous changes secondary to primary biliary cirrhosis(PBC).No case of granulomatous lung disease secondary to PBC misdiagnosed as lung cancer had been reported.CASE SUMMARY A middle-aged woman presented with lung nodules and was misdiagnosed with lung cancer by positron emission tomography/computed tomography.She underwent left lobectomy,and the pathology of the nodules showed granulomatous inflammation,which was then treated with antibiotics.However,a new nodule appeared.Further investigation with lung biopsy and liver serology led to the diagnosis of PBC,and chest computed tomography indicated significant reduction in the pulmonary nodule by treatment with methylprednisolone and ursodeoxycholic acid.CONCLUSION Diagnosis of pulmonary nodules requires integrating various clinical data to avoid unnecessary pulmonary lobectomy.

Pulmonary rehabilitation protocols in urgent lung transplantation patients

BACKGROUND:Prolonged invasive respiratory support and extracorporeal membrane oxygenation(ECMO)in patients requiring urgent lung transplantation(ULTx)present signifi cant challenges to clinical practice due to severe underlying diseases and complex conditions.The aim of the study was to report the clinical outcomes of patients who received ULTx and followed the perioperative rehabilitation protocol implemented in a lung transplant center.METHODS:A retrospective analysis was conducted in ULTx patients who required preoperative invasive mechanical ventilation(IMV)and ECMO between January 2018 and January 2023.Data were retrieved from electronic medical records at our lung transplant center.RESULTS:Fourteen patients(mean age 57.43±10.97 years;12 males,2 females)underwent ULTx with bridging ECMO and IMV.The mean body mass index was 23.94±3.33 kg/m²,and the mean Acute Physiology and Chronic Health Evaluation(APACHE)II score was 21.50±3.96.The Nutritional Risk Screening 2002(NRS 2002)scores were≥3.ULTx was performed after an 8.5-day waiting period(interquartile interval[IQR]5.0-26.5 d).Following the surgeries,the average lengths of ECMO and IMV were 1.0(IQR 1.0-2.0)d and 5.0(IQR 3.0-7.3)d,respectively.The total length of hospital stay was 60.1±30.8 d,with an average intensive care unit stay of 38.3±22.9 d and post-operative hospitalization stay of 45.8±26.1 d.Two patients died within 30 d after ULTx,with a 30-day survival rate of 85.71%.CONCLUSION:Patients receiving ULTx showed an acceptable short-term survival rate,validating the practicality and safety of the treatment protocols implemented in our center.

Clinical evolution of antisynthetase syndrome-associated interstitial lung disease after COVID-19 in a man with Klinefelter syndrome:A case report

BACKGROUND This study presents a case of rapidly developing respiratory failure due to antisynthetase syndrome(AS)following coronavirus disease 2019(COVID-19)in a 33-year-old man diagnosed with Klinefelter syndrome(KS).CASE SUMMARY A 33-year-old man with a diagnosis of KS was admitted to the Department of Pulmonary and Critical Care Medicine of a tertiary hospital in China for fever and shortness of breath 2 wk after the onset of COVID-19.Computed tomography of both lungs revealed diffuse multiple patchy heightened shadows in both lungs,accompanied by signs of partial bronchial inflation.Metagenomic next-generation sequencing of the bronchoalveolar lavage fluid suggested absence of pathogen.A biopsy specimen revealed organizing pneumonia with alveolar septal thickening.Additionally,extensive auto-antibody tests showed strong positivity for anti-SSA,anti-SSB,anti-Jo-1,and anti-Ro-52.Following multidisciplinary discussions,the patient received a final diagnosis of AS,leading to rapidly progressing respiratory failure.CONCLUSION This study underscores the clinical progression of AS-associated interstitial lung disease subsequent to viral infections such as COVID-19 in patients diagnosed with KS.

Systemic juvenile idiopathic arthritis–associated lung disease: A retrospective cohort study

BACKGROUND Lung damage in systemic juvenile arthritis(sJIA)is one of the contemporary topics in pediatric rheumatology.Several previous studies showed the severe course and fatal outcomes in some patients.The information about interstitial lung disease(ILD)in the sJIA is scarce and limited to a total of 100 cases.AIM To describe the features of sJIA patients with ILD in detail.METHODS In the present retrospective cohort study,information about 5 patients less than 18-years-old with sJIA and ILD were included.The diagnosis of sJIA was made according to the current 2004 and new provisional International League of Associations for Rheumatology criteria 2019.ILD was diagnosed with chest computed tomography with the exclusion of other possible reasons for concurrent lung involvement.Macrophage activation syndrome(MAS)was diagnosed with HLH-2004 and 2016 EULAR/ACR/PRINTO Classification Criteria and hScores were calculated during the lung involvement.RESULTS The onset age of sJIA ranged from 1 year to 10 years.The time interval before ILD ranged from 1 mo to 3 years.The disease course was characterized by the prevalence of the systemic features above articular involvement,intensive rash(100%),persistent and very active MAS(hScore range:194-220)with transaminitis(100%),and respiratory symptoms(100%).Only 3 patients(60%)developed a clubbing phenomenon.All patients(100%)had pleural effusion and 4 patients(80%)had pericardial effusion at the disease onset.Two patients(40%)developed pulmonary arterial hypertension.Infusion-related reactions to tocilizumab were observed in 3(60%)of the patients.One patient with trisomy 21 had a fatal disease course.Half of the remaining patients had sJIA remission and 2 patients had improvement.Lung disease improved in 3 patients(75%),but 1 of them had initial deterioration of lung involvement.One patient who has not achieved the sJIA remission had the progressed course of ILD.No cases of hyper-eosinophilia were noted.Four patients(80%)received canakinumab and one(20%)tocilizumab at the last follow-up visit.CONCLUSION ILD is a severe life-threatening complication of sJIA that may affect children of different ages with different time intervals since the disease onset.Extensive rash,serositis(especially pleuritis),full-blown MAS with transaminitis,lymphopenia,trisomy 21,eosinophilia,and biologic infusion reaction are the main predictors of ILD.The following studies are needed to find the predictors,pathogenesis,and treatment options,for preventing and treating the ILD in sJIA patients.

Resveratrol extracted from Chinese herbal medicines: A novel therapeutic strategy for lung diseases

Lung diseases and their related complications represent a critical source of morbidity and mortality globally and have become a research focus in recent years.There are plenty of hazards that threaten the health of lung by exposure to external environmental stimuli,such as dust,cigarette smoke,PM2.5,air pollution and pathogen infection.These risks lead to the impairment of lung function and subsequent lung diseases including pneumonia,chronic obstructive pulmonary disease(COPD),asthma and idiopathic pulmonary fibrosis(IPF).Compared with antibiotics and corticosteroids therapies,traditional Chinese medicine prescriptions are more effective with fewer side effects.A considerable variety of bioactive ingredients have been extracted and identified from Chinese herbal medicines and are used for the treatment of different lung diseases,including resveratrol.Increasing studies have reported promising therapeutic effects of resveratrol against lung diseases by inhibiting oxidative stress,inflammation,aging,fibrosis and cancer both in vitro and in vivo.In this review,the recent progress in the studies of lungprotective effects and underlying mechanisms of resveratrol and also highlight the potency of resveratrol and traditional Chinese prescriptions containing resveratrol as promising therapeutic options were summarized for the treatment of lung and respiratory diseases.

Role of extracellular vesicles in lung diseases

Extracellular vesicles(EVs)are anuclear particles composed of lipid bilayers that contain nucleic acids,proteins,lipids,and organelles.EVs act as an important mediator of cell-to-cell communication by transmitting biological signals or components,including lipids,proteins,messenger RNAs,DNA,microRNAs,organelles,etc,to nearby or distant target cells to activate and regulate the function and phenotype of target cells.Under physiological conditions,EVs play an essential role in maintaining the homeostasis of the pulmonary milieu but they can also be involved in promoting the pathogenesis and progression of various respiratory diseases including chronic obstructive pulmonary disease,asthma,acute lung injury/acute respiratory distress syndrome,idiopathic pulmonary fibrosis(IPF),and pulmonary artery hypertension.In addition,in multiple preclinical studies,EVs derived from mesenchymal stem cells(EVs)have shown promising therapeutic effects on reducing and repairing lung injuries.Furthermore,in recent years,researchers have explored different methods for modifying EVs or enhancing EVs-mediated drug delivery to produce more targeted and beneficial effects.This article will review the characteristics and biogenesis of EVs and their role in lung homeostasis and various acute and chronic lung diseases and the potential therapeutic application of EVs in the field of clinical medicine.

Recent applications and strategies in nanotechnology for lung diseases

Lung diseases,including COVID-19 and lung cancers,is a huge threat to human health.However,for the treatment and diagnosis of various lung diseases,such as pneumonia,asthma,cancer,and pulmonary tuberculosis,are becoming increasingly challenging.Currently,several types of treatments and/or diagnostic methods are used to treat lung diseases;however,the occurrence of adverse reactions to chemotherapy,drug-resistant bacteria,side effects that can be significantly toxic,and poor drug delivery necessitates the development of more promising treatments.Nanotechnology,as an emerging technology,has been extensively studied in medicine.Several studies have shown that nano-delivery systems can significantly enhance the targeting of drug delivery.When compared to traditional delivery methods,several nanoparticle delivery strategies are used to improve the detection methods and drug treatment efficacy.Transporting nanoparticles to the lungs,loading appropriate therapeutic drugs,and the incorporation of intelligent functions to overcome various lung barriers have broad prospects as they can aid in locating target tissues and can enhance the therapeutic effect while minimizing systemic side effects.In addition,as a new and highly contagious respiratory infection disease,COVID-19 is spreading worldwide.However,there is no specific drug for COVID-19.Clinical trials are being conducted in several countries to develop antiviral drugs or vaccines.In recent years,nanotechnology has provided a feasible platform for improving the diagnosis and treatment of diseases,nanotechnology-based strategies may have broad prospects in the diagnosis and treatment of COVID-19.This article reviews the latest developments in nanotechnology drug delivery strategies in the lungs in recent years and studies the clinical application value of nanomedicine in the drug delivery strategy pertaining to the lung.

Mechanism prediction of Astragalus mongholicus Bunge and Angelica sinensis Diels in treating interstitial lung disease based on network pharmacology and molecular docking

Objective:To investigate the mechanism by which Astragalus mongholicus Bunge(AM),and Angelica sinensis Diels(AS)act in interstitial lung disease(ILD)based on computational prediction.Methods:We screened the ingredients of AM and AS in PubMed,the Web of Science,China National Knowledge Infrastructure(CNKI)Databases,etc.Then obtained the potential effective components.By sharing the same molecular with ILD,we got the possible target genes for ILD treatment and constructed components–targets–disease network with Cytoscape software.The CTD(Comparative Toxicogenomics Database)database was used for GO and KEGG enrichment analysis of these target genes.Results:59 active ingredients that can be druggable were chosen from AM,67 active ingredients were chosen from AS.77 overlapping target genes for AM and ILD and 36 overlapping target genes for AS and ILD were acquired.The hub targets of AM were PTGS2,PTGS1,CDK2,MAOA,ESR1,TOP2A,GSK3B,ESR2,PPARG,NOS2,The hub targets of AS were PTGS2,GABRA1,PTGS1,CHRM1,SLC6A2,ADRA1B,ADRAIA,ADRB2,CHRM3,GABRA2,CHRM2.Quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,and 5-Hydroxycoumarin were the main active ingredients which have more effective targets.Prediction of the protein-protein interaction network showed PTGS2,GSK3B,PPARG,etc.,were the important predicted targets.The enriched KEGG pathways,including the Immune System,Metabolism of lipids and lipoproteins,Cytokine Signaling in the Immune system,Generic Transcription Pathway,The interleukin pathway,Metabolism of proteins,PI3K-Akt signaling pathway,Metabolic pathways,Innate Immune System,Neuroactive ligand-receptor interaction,Metabolism,GPCR downstream signaling,Amine ligand-binding receptors,Class A/1,Calcium signaling pathway.Molecular docking showed that quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,5-Hydroxycoumarin had good binding activities with PTGS2 and GSK3B,which mainly mediated PI3K/Akt and other important signaling pathways in the pathogenesis of ILD.Conclusion:The components in AS and AM share some common targets,such as PTGS2.AM and AS may ameliorate ILD through the PI3K-Akt signaling pathway which is mediated by GSK3B.PTGS2,PPARG may also be vital target genes in the treatment of ILD with AM and AS.

A Validated Model for the Imaging Diagnosis of Cystic Lung Disease

Rationale and Objectives: Cystic lung disease may be accurately diagnosed by imaging interpretation of specialist radiologists, without other information. We hypothesized that with minimal training non-specialists could perform similarly to specialist physicians in the diagnosis of cystic lung disease. Methods: 72 cystic lung disease cases and 25 cystic lung disease mimics were obtained from three sources: 1) a prospective acquired diffuse lung disease registry, 2) a retrospective search of medical records and 3) teaching files. Cases were anonymized, randomized and interpreted by 7 diffuse lung disease specialists and 15 non-specialist radiologists and pulmonologists. Clinical information other than age and sex was not provided. Prior to interpretation, non-specialists viewed a short PDF training document explaining cystic lung disease interpretation. Results: Correct first choice diagnosis of 85%-88% may be achieved by high-performing specialist readers and 71%-80% by non-specialists and lower-performing specialists, with mean accuracies in the diagnosis of LAM (91%, p Conclusion: With specific but limited training, non-specialist physicians can diagnose cystic lung diseases from CT appearance alone with similar accuracy to specialists, correctly identifying approximately 75% of cases.

Expert Consensus on the Diagnosis and Treatment of Anticancer Drug-Induced Interstitial Lung Disease

Drug-induced interstitial lung disease(DILD)is the most common pulmonary adverse event of anticancer drugs.In recent years,the incidence of anticancer DILD has gradually increased with the rapid development of novel anticancer agents.Due to the diverse clinical manifestations and the lack of specific diagnostic criteria,DILD is difficult to diagnose and may even become fatal if not treated properly.Herein,a multidisciplinary group of experts from oncology,respiratory,imaging,pharmacology,pathology,and radiology departments in China has reached the“expert consensus on the diagnosis and treatment of anticancer DILD”after several rounds of a comprehensive investigation.This consensus aims to improve the awareness of clinicians and provide recommendations for the early screening,diagnosis,and treatment of anticancer DILD.This consensus also emphasizes the importance of multidisciplinary collaboration while managing DILD.

Diffuse cystic lung diseases

Diffuse cystic lung diseases are uncommon but can present a diagnostic challenge because increasing number of diseases have been associated with this presentation.Cyst in the lung is defined as a round parenchymal lucency with a well-defined thin wall(<2 mm thickness).Focal or multifocal cystic lesions include blebs,bullae,pneumatoceles,congenital cystic lesions,traumatic lesions,and several infectious processes such as coccidioidomycosis,Pneumocystis jiroveci pneumonia,and hydatid disease.“Diffuse”distribution in the lung implies involvement of all lobes.Diffuse lung involvement with cystic lesions can be seen in pulmonary lymphangioleiomyomatosis,pulmonary Langerhans’cell histiocytosis,lymphoid interstitial pneumonia,Birt-Hogg-Dubésyndrome,amyloidosis,light chain deposition disease,honeycomb lung associated with advanced fibrosis,and several other rare causes including metastatic disease.High-resolution computed tomography of the chest helps define morphologic features of the lung lesions as well as their distribution and associated features such as intrathoracic lymphadenopathy.Correlating the tempo of the disease process and clinical context with chest imaging findings serve as important clues to defining the underlying nature of the cystic lung disease and guide diagnostic evaluation as well as management.

Association between the Lung Immune Prognostic Index and mortality in patients with idiopathic inflammatory myopathy-associated interstitial lung disease

Objective:To explore the association between the Lung Immune Prognostic Index(LIPI)and 1-year all-cause mortality in patients with idiopathic inflammatory myopathy related interstitial lung disease(IIM-ILD).Methods:Patients who were diagnosed with IIM-ILD at West China Hospital,Sichuan University from January 2008 to December 2021 were retrospectively included and categorized into three groups based on LIPI.Univariable and multivariable Cox proportional hazards models were conducted to explore potential association between the LIPI and patients'mortality.Results:A total of 1116 patients were screened,and 830 were included in this study.The multivariable Cox analysis showed that,compared with patients with poor LIPI,the hazard ratio(HR)for all-cause 1-year mortality was 0.22(95%CI 0.05-0.93,P=0.04)for patients in the good LIPI group(LDH<250 IU/L and dNLR<3).After excluding patients lost to follow-up within one year,a similar result was found for LIPI(HR 0.20,95%CI 0.05-0.86;P=0.03).Conclusions:Good LIPI was independently associated with decreased risk of all-cause 1-year mortality in patients with IIM-ILD.This easy-to-obtain index might be served as a potential marker for assessing the prognosis of IIM-ILD.

Anti-melanoma differentiation-associated gene 5 and anti-Ro52 antibody-dual positive dermatomyositis accompanied by rapidly lung disease:Three case reports

BACKGROUND Clinically amyopathic deramatomyositis was manifested as the various cutaneous dermatomyositis(DM)manifestations without muscle weakness.Anti-melanoma differentiation-associated gene 5(anti-MDA5)and anti-Ro52 antibody-dual positive clinically amyopathic DM patients are at a high risk of developing rapidly progressive interstitial lung disease,and they exhibit an immensely high half-year mortality.CASE SUMMARY We presented three patients with anti-MDA5 and anti-Ro52 antibody-dual positive DM patients and we reviewed the previous studies on the link between anti-MDA5 and anti-Ro52 antibody-dual positive DM.Although we aggressively treated these patients similarly,but they all exhibited different prognoses.We reviewed the importance of clinical cutaneous rashes as well as the pathogenesis and treatment in the dual positive anti-MDA5 and anti-Ro52 associated DM.CONCLUSION Patients with anti-MDA5 anti-Ro52 antibody-dual positive DM should be accurately diagnosed at an early stage and should be treated aggressively,thus,the patient’s prognosis can be significantly modified.

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.

Mechanism prediction of Astragalus mongholicus Bunge and Angelica sinensis Diels in treating interstitial lung disease based on network pharmacology and molecular docking

Objective:To investigate the mechanism by which Astragalus mongholicus Bunge(AM),and Angelica sinensis Diels(AS)act in interstitial lung disease(ILD)based on computational prediction.Methods:We screened the ingredients of AM and AS in PubMed,the Web of Science,China National Knowledge Infrastructure(CNKI)Databases,etc.Then obtained the potential effective components.By sharing the same molecular with ILD,we got the possible target genes for ILD treatment and constructed components–targets–disease network with Cytoscape software.The CTD(Comparative Toxicogenomics Database)database was used for GO and KEGG enrichment analysis of these target genes.Results:59 active ingredients that can be druggable were chosen from AM,67 active ingredients were chosen from AS.77 overlapping target genes for AM and ILD and 36 overlapping target genes for AS and ILD were acquired.The hub targets of AM were PTGS2,PTGS1,CDK2,MAOA,ESR1,TOP2A,GSK3B,ESR2,PPARG,NOS2,The hub targets of AS were PTGS2,GABRA1,PTGS1,CHRM1,SLC6A2,ADRA1B,ADRAIA,ADRB2,CHRM3,GABRA2,CHRM2.Quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,and 5-Hydroxycoumarin were the main active ingredients which have more effective targets.Prediction of the protein-protein interaction network showed PTGS2,GSK3B,PPARG,etc.,were the important predicted targets.The enriched KEGG pathways,including the Immune System,Metabolism of lipids and lipoproteins,Cytokine Signaling in the Immune system,Generic Transcription Pathway,The interleukin pathway,Metabolism of proteins,PI3K-Akt signaling pathway,Metabolic pathways,Innate Immune System,Neuroactive ligand-receptor interaction,Metabolism,GPCR downstream signaling,Amine ligand-binding receptors,Class A/1,Calcium signaling pathway.Molecular docking showed that quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,5-Hydroxycoumarin had good binding activities with PTGS2 and GSK3B,which mainly mediated PI3K/Akt and other important signaling pathways in the pathogenesis of ILD.Conclusion:The components in AS and AM share some common targets,such as PTGS2.AM and AS may ameliorate ILD through the PI3K-Akt signaling pathway which is mediated by GSK3B.PTGS2,PPARG may also be vital target genes in the treatment of ILD with AM and AS.

Cutaneous Cryptococcosis Arising in a Patient with Idiopathic Lung Disease: Related Illnesses or “Ticks and Fleas”

Cryptococcus is a yeast typically found in bird feces such as pigeon droppings. Infection may occur through inhalation of spores or via direct inoculation into the skin. Typically there is a history of immunosuppression, but cases are also reported in immunocompetent hosts. Cryptococcus may manifest as pulmonary disease or primary cutaneous infection, but dissemination to a systemic illness is the most life-threatening concern. We present the case of a 71-year-old man with a four-year history of idiopathic lung disease, treated with oral prednisone and mycophenolate, presents with a new onset skin rash on the right wrist. He has a history of cleaning and clearing barns and sheds after a recent storm devastated the area. Birds and bats were present in these structures while he was working. Initial therapy failed, and subsequent biopsy showed the presence of Cryptococcus yeast. Further investigation yielded a positive, low titer Cryptococcus antigen screen but negative blood cultures. This case illustrates three valuable facets of patient care. Ideally, one diagnosis will explain all of the clinical presentation, but when that is not the case then multiple etiologies must be explored. Sometimes first-line therapy is ineffective, and the clinician should not be afraid to recognize that and change course. Importantly with skin lesions, failure to respond to treatment or worsening of the lesion in the face of topical and/or oral steroids should lead one to consider the possibility of infection, particularly in an immunosuppressed patient, and prompt biopsy is prudent.