Pulmonary artery stent thrombosis and symptomatic pulmonary hypertension following COVID-19 infection in Alagille patient:A case report

BACKGROUND Alagille syndrome is a multisystem disease that results in various vascular anomalies,commonly involving the cardiac and pulmonary systems.To the best of our knowledge,there is no literature regarding the cardiovascular outcomes of these patients in association with coronavirus disease 2019(COVID-19).CASE SUMMARY A 34-year-old woman with a history of Alagille syndrome who underwent successful atrial septal defect with partial anomalous pulmonary veins and patent ductus arteriosus repair,as well as left pulmonary artery catheterization and stenting in childhood due to pulmonary stenosis.The patient was without any respiratory symptoms and was a dancer prior to contracting COVID-19.Several weeks after her COVID-19 infection,she developed left pulmonary artery stent thrombosis and subsequent symptomatic pulmonary hypertension.A treatment strategy of anticoagulation alongside pharmacological agents for pulmonary hypertension for 3 months followed by balloon pulmonary artery angioplasty to reopen the stenosis was unsuccessful.CONCLUSION In the era of COVID-19,patients with pulmonary vascular malformations and endovascular stents are at an increased risk for chronic thromboembolic disease.Patients may benefit from prophylactic antiplatelet or anticoagulation therapy.Stent thrombosis is a devastating phenomenon and should be treated urgently and aggressively with balloon pulmonary angioplasty,and/or a thrombolytic agent.

Pulmonary embolism after shoulder surgery:Is it a real threat?

Pulmonary embolism(PE)is a rare but devastating complication of shoulder surgery.Apart from increased morbidity and mortality rates,it may significantly impair postoperative recovery and functional outcome.Its frequency accounts for up to 5.7%of all shoulder surgery procedures with a higher occurrence in women and patients older than 70 years.It is most commonly associated with thrombophilia,diabetes mellitus,obesity,smoking,hypertension,and a history of malignancy.PE usually occurs secondary to upper or lower-extremity deep vein thrombosis(DVT).However,in rare cases,the source of the thrombi cannot be determined.Prophylaxis for PE following shoulder surgery remains a topic of debate,and the standard of care does not routinely require prophylactic medication for DVT prophylaxis.Early ambulation and elastic stockings are important preventative measures for DVT of the lower extremity and medical agents such as aspirin,low-molecular-weight heparin,and vitamin K antagonists are indicated for high-risk patients,long-lasting operations,or concomitant severe acute respiratory syndrome coronavirus 2 infection.The most common symptoms of PE include chest pain and shortness of breath,but PE can also be asymptomatic in patients with intrinsic tolerance of hypoxia.Patients with DVT may also present with swelling and pain of the respective extremity.The treatment of PE includes inpatient or outpatient anticoagulant therapy if the patient is hemodynamically unstable or stable,respectively.Hemodynamic instability may require transfer to the intensive care unit,and cardiovascular arrest can be implicated in fatal events.An important issue for patients with PE in the postoperative period after shoulder surgery is residual stiffness due to a delay in rehabilitation and a prolonged hospital stay.Early physiotherapy and range-of-motion exercises do not adversely affect the prognosis of PE and are highly recommended to preserve shoulder mobility and function.

Thrombolysis and extracorporeal cardiopulmonary resuscitation for cardiac arrest due to pulmonary embolism:A case report

BACKGROUND Cardiac arrest caused by acute pulmonary embolism(PE)is the most serious clinical circumstance,necessitating rapid identification,immediate cardiopulmonary resuscitation(CPR),and systemic thrombolytic therapy.Extracorporeal CPR(ECPR)is typically employed as a rescue therapy for selected patients when conventional CPR is failing in settings where it can be implemented.CASE SUMMARY We present a case of a 69-year-old male who experienced a prolonged cardiac arrest in an ambulance with pulseless electrical activity.Upon arrival at the emergency department with ongoing manual chest compressions,bedside pointof-care ultrasound revealed an enlarged right ventricle without contractility.Acute PE was suspected as the cause of cardiac arrest,and intravenous thrombolytic therapy with 50 mg tissue plasminogen activator was administered during mechanical chest compressions.Despite 31 minutes of CPR,return of spontaneous circulation was not achieved until 8 minutes after initiation of Veno-arterial extracorporeal membrane oxygenation(ECMO)support.Under ECMO support,the hemodynamic status and myocardial contractility significantly improved.However,the patient ultimately did not survive due to intracerebral hemorrhagic complications,leading to death a few days later in the hospital.CONCLUSION This case illustrates the potential of combining systemic thrombolysis with ECPR for refractory cardiac arrest caused by acute PE,but it also highlights the increased risk of significant bleeding complications,including fatal intracranial hemorrhage.

Study on the efficacy of early treatment with pirfenidone on the lung function of patients with idiopathic pulmonary fibrosis

BACKGROUND Idiopathic pulmonary fibrosis(IPF)is classified under fibrotic interstitial pneumonia,characterized by a chronic and progressive course.The predominant clinical features of IPF include dyspnea and pulmonary dysfunction.AIM To assess the effects of pirfenidone in the early treatment of IPF on lung function in patients.METHODS A retrospective analysis was performed on 113 patients with IPF who were treated in our hospital from November 2017 to January 2023.These patients were divided into two groups:control group(n=53)and observation group(n=60).In the control group,patients received routine therapy in combination with methylprednisolone tablets,while those in the observation group received routine therapy together with pirfenidone.After applying these distinct treatment approaches to the two groups,we assessed several parameters,including the overall effectiveness of clinical therapy,the occurrence of adverse reactions(e.g.,nausea,vomiting,and anorexia),symptom severity scores,pulmonary function index levels,inflammatory marker levels,and the 6-min walk distance before and after treatment in both groups.RESULTS The observation group exhibited significantly higher rates than the control group after therapy,with a clear distinction(P<0.05).After treatment,the observation group experienced significantly fewer adverse reactions than the control group,with a noticeable difference(P<0.05).When analyzing the symptom severity scores between the two groups of patients after treatment,the observation group had significantly lower scores than the control group,with a distinct difference(P<0.05).When comparing the pulmonary function index levels between the two groups of patients after therapy,the observation group displayed significantly higher levels than the control group,with a noticeable difference(P<0.05).Evaluating the inflammatory marker data(C-reactive protein,interleukin-2[IL-2],and IL-8)between the two groups of patients after therapy,the observation group exhibited significantly lower levels than the control group,with significant disparities(P<0.05).Comparison of the 6-min walking distance data between the two groups of patients after treatment showed that the observation group achieved significantly greater distances than the control group,with a marked difference(P<0.05).CONCLUSION Prompt initiation of pirfenidone treatment in individuals diagnosed with IPF can enhance pulmonary function,elevate inflammatory factor levels,and increase the distance covered in the 6-min walk test.This intervention is conducive to effectively decreasing the occurrence of adverse reactions in patients.

Analysis of the influencing factors and clinical related characteristics of pulmonary tuberculosis in patients with type 2 diabetes mellitus

BACKGROUND In China,the prevalence of type 2 diabetes mellitus(T2DM)among diabetic patients is estimated to be between 90%-95%.Additionally,China is among the 22 countries burdened by a high number of tuberculosis cases,with approximately 4.5 million individuals affected by active tuberculosis.Notably,T2DM poses a significant risk factor for the development of tuberculosis,as evidenced by the increased incidence of T2DM coexisting with pulmonary tuberculosis(T2DMPTB),which has risen from 19.3%to 24.1%.It is evident that these two diseases are intricately interconnected and mutually reinforcing in nature.AIM To elucidate the clinical features of individuals diagnosed with both T2DM and tuberculosis(T2DM-PTB),as well as to investigate the potential risk factors associated with active tuberculosis in patients with T2DM.METHODS T2DM-PTB patients who visited our hospital between January 2020 and January 2023 were selected as the observation group,Simple DM patients presenting to our hospital in the same period were the control group,Controls and case groups were matched 1:2 according to the principle of the same sex,age difference(±3)years and disease duration difference(±5)years,patients were investigated for general demographic characteristics,diabetes-related characteristics,body immune status,lifestyle and behavioral habits,univariate and multivariate analysis of the data using conditional logistic regression,calculate the odds ratio(OR)values and 95%CI of OR values.RESULTS A total of 315 study subjects were included in this study,including 105 subjects in the observation group and 210 subjects in the control group.Comparison of the results of both anthropometric and biochemical measures showed that the constitution index,systolic blood pressure,diastolic blood pressure and lymphocyte count were significantly lower in the case group,while fasting blood glucose and high-density lipoprotein cholesterol levels were significantly higher than those in the control group.The results of univariate analysis showed that poor glucose control,hypoproteinemia,lymphopenia,TB contact history,high infection,smoking and alcohol consumption were positively associated with PTB in T2DM patients;married,history of hypertension,treatment of oral hypoglycemic drugs plus insulin,overweight,obesity and regular exercise were negatively associated with PTB in T2DM patients.Results of multivariate stepwise regression analysis found lymphopenia(OR=17.75,95%CI:3.40-92.74),smoking(OR=12.25,95%CI:2.53-59.37),history of TB contact(OR=6.56,95%CI:1.23-35.03)and poor glycemic control(OR=3.37,95%CI:1.11-10.25)was associated with an increased risk of developing PTB in patients with T2DM,While being overweight(OR=0.23,95%CI:0.08-0.72)and obesity(OR=0.11,95%CI:0.02-0.72)was associated with a reduced risk of developing PTB in patients with T2DM.CONCLUSION T2DM-PTB patients are prone to worse glycemic control,higher infection frequency,and a higher proportion of people smoking,drinking alcohol,and lack of exercise.Lymphopenia,smoking,history of TB exposure,poor glycemic control were independent risk factors for T2DM-PTB,and overweight and obesity were associated with reduced risk of concurrent PTB in patients with T2DM.

Tanshinone IIA ameliorates energy metabolism dysfunction of pulmonary fibrosis using 13C metabolic flux analysis

Evidence indicates that metabolic reprogramming characterized by the changes in cellular metabolic patterns contributes to the pathogenesis of pulmonary fibrosis (PF). It is considered as a promising therapeutic target anti-PF. The well-documented against PF properties of Tanshinone IIA (Tan IIA) have been primarily attributed to its antioxidant and anti-inflammatory potency. Emerging evidence suggests that Tan IIA may target energy metabolism pathways, including glycolysis and tricarboxylic acid (TCA) cycle. However, the detailed and advanced mechanisms underlying the anti-PF activities remain obscure. In this study, we applied [U-13C]-glucose metabolic flux analysis (MFA) to examine metabolism flux disruption and modulation nodes of Tan IIA in PF. We identified that Tan IIA inhibited the glycolysis and TCA flux, thereby suppressing the production of transforming growth factor-β1 (TGF-β1)-dependent extracellular matrix and the differentiation and proliferation of myofibroblasts in vitro. We further revealed that Tan IIA inhibited the expression of key metabolic enzyme hexokinase 2 (HK2) by inhibiting phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor 1α (HIF-1α) pathway activities, which decreased the accumulation of abnormal metabolites. Notably, we demonstrated that Tan IIA inhibited ATP citrate lyase (ACLY) activity, which reduced the collagen synthesis pathway caused by cytosol citrate consumption. Further, these results were validated in a mouse model of bleomycin-induced PF. This study was novel in exploring the mechanism of the occurrence and development of Tan IIA in treating PF using 13C-MFA technology. It provided a novel understanding of the mechanism of Tan IIA against PF from the perspective of metabolic reprogramming.

Spatially resolved metabolomics visualizes heterogeneous distribution of metabolites in lung tissue and the anti-pulmonary fibrosis effect of Prismatomeris connate extract

Pulmonary fibrosis (PF) is a chronic progressive end-stage lung disease. However, the mechanisms underlying the progression of this disease remain elusive. Presently, clinically employed drugs are scarce for the treatment of PF. Hence, there is an urgent need for developing novel drugs to address such diseases. Our study found for the first time that a natural source of Prismatomeris connata Y. Z. Ruan (Huang Gen, HG) ethyl acetate extract (HG-2) had a significant anti-PF effect by inhibiting the expression of the transforming growth factor beta 1/suppressor of mothers against decapentaplegic (TGF-β1/Smad) pathway. Network pharmacological analysis suggested that HG-2 had effects on tyrosine kinase phosphorylation, cellular response to reactive oxygen species, and extracellular matrix (ECM) disassembly. Moreover, mass spectrometry imaging (MSI) was used to visualize the heterogeneous distribution of endogenous metabolites in lung tissue and reveal the anti-PF metabolic mechanism of HG-2, which was related to arginine biosynthesis and alanine, asparate and glutamate metabolism, the downregulation of arachidonic acid metabolism, and the upregulation of glycerophospholipid metabolism. In conclusion, we elaborated on the relationship between metabolite distribution and the progression of PF, constructed the regulatory metabolic network of HG-2, and discovered the multi-target therapeutic effect of HG-2, which might be conducive to the development of new drugs for PF.

Organizing pneumonia secondary to pulmonary tuberculosis:A case report

BACKGROUND Organizing pneumonia secondary to pulmonary tuberculosis is rare.Moreover,the temporal boundary between pulmonary tuberculosis and secondary organizing pneumonia has not been defined.We report a case of secondary organizing pneumonia associated with pulmonary tuberculosis occurring after nine months of antituberculosis treatment.CASE SUMMARY A 54 years old man,previously diagnosed with pulmonary tuberculosis and tuberculous pleurisy,underwent nine months of antituberculosis treatment.Follow-up lung computed tomography revealed multiple new subpleural groundglass opacities in both lungs,and a lung biopsy confirmed organizing pneumonia.Treatment continued with anti-tuberculosis agents and hormone therapy,and subsequent dynamic pulmonary computed tomography exams demonstrated improvement in lesion absorption.No disease recurrence was observed after corticosteroid therapy discontinuation.CONCLUSION When treating patients with active pulmonary tuberculosis,if an increase in lesions is observed during anti-tuberculosis treatment,it is necessary to consider the possibility of tuberculosis-related secondary organizing pneumonia,timely lung biopsy is essential for early intervention.

Pulmonary alveolar proteinosis induced by X-linked agammaglobulinemia:A case report

BACKGROUND Pulmonary alveolar proteinosis(PAP)and X-linked agammaglobulinemia(XLA)are rare diseases in children.Many theories infer that immunodeficiency can induce PAP,but these reports are almost all review articles,and there is little clinical evidence.We report the case of a child with both PAP and XLA.CASE SUMMARY A 4-month-old boy sought medical treatment due to coughing and difficulty in breathing for>2 wk.He had been hospitalized multiple times due to respiratory infections and diarrhea.Chest computed tomography and alveolar lavage fluid showed typical PAP-related manifestations.Genetic testing confirmed that the boy also had XLA.Following total lung alveolar lavage and intravenous immunoglobulin replacement therapy,the boy recovered and was discharged.During the follow-up period,the number of respiratory infections was significantly reduced,and PAP did not recur.CONCLUSION XLA can induce PAP and improving immune function contributes to the prognosis of children with this type of PAP.

Therapeutic utility of human umbilical cord-derived mesenchymal stem cells-based approaches in pulmonary diseases:Recent advancements and prospects

Pulmonary diseases across all ages threaten millions of people and have emerged as one of the major public health issues worldwide.For diverse disease con-ditions,the currently available approaches are focused on alleviating clinical symptoms and delaying disease progression but have not shown significant therapeutic effects in patients with lung diseases.Human umbilical cord-derived mesenchymal stem cells(UC-MSCs)isolated from the human UC have the capacity for self-renewal and multilineage differentiation.Moreover,in recent years,these cells have been demonstrated to have unique advantages in the treatment of lung diseases.We searched the Public Clinical Trial Database and found 55 clinical trials involving UC-MSC therapy for pulmonary diseases,including coronavirus disease 2019,acute respiratory distress syndrome,bron-chopulmonary dysplasia,chronic obstructive pulmonary disease,and pulmonary fibrosis.In this review,we summarize the characteristics of these registered clinical trials and relevant published results and explore in depth the challenges and opportunitiesfaced in clinical application.Moreover,the underlying mole-cular mechanisms involved in UC-MSC-based therapy for pulmonary diseases are also analyzed in depth.In brief,this comprehensive review and detailed analysis of these clinical trials can be expected to provide a scientific reference for future large-scale clinical application.

Study on the impact of comprehensive geriatric assessment on anxiety and depression in chronic obstructive pulmonary disease patients

BACKGROUND Psychological factors such as anxiety and depression will not only aggravate the symptoms of chronic obstructive pulmonary disease(COPD)patients and reduce the quality of life of patients,but also affect the treatment effect and long-term prognosis.Therefore,it is of great significance to explore the clinical application of senile comprehensive assessment in the treatment of COPD and its influence on psychological factors such as anxiety and depression.AIM To explore the clinical application of comprehensive geriatric assessment in COPD care and its impact on anxiety and depression in elderly patents.METHODS In this retrospective study,60 patients with COPD who were hospitalized in our hospital from 2019 to 2020 were randomly divided into two groups with 30 patients in each group.The control group was given routine nursing,and the observation group was given comprehensive assessment.Clinical symptoms,quality of life[COPD assessment test(CAT)score],anxiety and depression Hamilton Anxiety Rating Scale(HAMA)and Hamilton Depression Rating Scale(HAMD)were compared between the two groups.RESULTS CAT scores in the observation group decreased from an average of 24.5 points at admission to an average of 18.3 points at discharge,and in the control group from an average of 24.7 points at admission to an average of 18.3 points at discharge.The average score was 22.1(P<0.05).In the observation group,HAMA scores decreased from 14.2 points at admission to 8.6 points at discharge,and HAMD scores decreased from 13.8 points at admission to 7.4 points at discharge.The mean HAMD scores in the control group decreased from an average of 14.5 at admission to an average of 12.3 at discharge,and from an average of 14.1 at admission to an average of 11.8 at discharge.CONCLUSION The application of comprehensive geriatric assessment in COPD care has a significant effect on improving patients'clinical symptoms and quality of life,and can effectively reduce patients'anxiety and depression.

Effects of acetylcysteine on micro-inflammation and pulmonary ventilation in chronic obstructive pulmonary disease exacerbation

BACKGROUND Acute exacerbation of chronic obstructive pulmonary disease(AECOPD)is a serious complication of chronic obstructive pulmonary disease,often characterized by increased morbidity and mortality.In traditional Chinese medicine,AECOPD is linked to phlegm-heat and blood-stasis,presenting symptoms like thick sputum,fever,and chest pain.It has been shown that acetylcysteine inhalation in conjunction with conventional therapy significantly reduced inflammatory markers and improved lung function parameters in patients with AECOPD,suggesting that acetylcysteine may be an important adjunctive therapy for patients with phlegm-heat-blood stasis type AECOPD.AIM To investigate the effect of acetylcysteine on microinflammation and lung ventilation in patients with phlegm-heat and blood-stasis-type AECOPD.METHODS One hundred patients with phlegm-heat and blood-stasis-type AECOPD were randomly assigned to two groups.The treatment group received acetylcysteine inhalation(10%solution,5 mL,twice daily)along with conventional therapy,whereas the control group received only conventional therapy.The treatment duration was 14 d.Inflammatory markers(C-reactive protein,interleukin-6,and tumor necrosis factor-alpha)in the serum and sputum as well as lung function parameters(forced expiratory volume in one second,forced vital capacity,and peak expiratory flow)were assessed pre-and post-treatment.Acetylcysteine inhalation led to significant reductions in inflammatory markers and improvements in lung function parameters compared to those in the control group(P<0.05).This suggests that acetylcysteine could serve as an effective adjunct therapy for patients with phlegm-heat and blood-stasis-type AECOPD.RESULTS Acetylcysteine inhalation significantly reduced inflammatory markers in the serum and sputum and improved lung ventilation function parameters in patients with phlegm-heat and blood-stasis type AECOPD compared with the control group.These differences were statistically significant(P<0.05).The study concluded that acetylcysteine inhalation had a positive effect on microinflammation and lung ventilation function in patients with this type of AECOPD,suggesting its potential as an adjuvant therapy for such cases.CONCLUSION Acetylcysteine inhalation demonstrated significant improvements in reducing inflammatory markers in the serum and sputum,as well as enhancing lung ventilation function parameters in patients with phlegm-heat and bloodstasis type AECOPD.These findings suggest that acetylcysteine could serve as a valuable adjuvant therapy for individuals with this specific type of AECOPD,offering benefits for managing microinflammation and optimizing lung function.

Microvesicles derived from mesenchymal stem cells inhibit acute respiratory distress syndrome-related pulmonary fibrosis in mouse partly through hepatocyte growth factor

BACKGROUND Pulmonary fibrosis is one of the main reasons for the high mortality rate among acute respiratory distress syndrome(ARDS)patients.Mesenchymal stromal cell-derived microvesicles(MSC-MVs)have been shown to exert antifibrotic effects in lung diseases.AIM To investigate the effects and mechanisms of MSC-MVs on pulmonary fibrosis in ARDS mouse models.METHODS MSC-MVs with low hepatocyte growth factor(HGF)expression(siHGF-MSC-MVs)were obtained via lentivirus transfection and used to establish the ARDS pulmonary fibrosis mouse model.Following intubation,respiratory mechanics-related indicators were measured via an experimental small animal lung function tester.Homing of MSC-MVs in lung tissues was investigated by near-infrared live imaging.Immunohistochemical,western blotting,ELISA and other methods were used to detect expression of pulmonary fibrosis-related proteins and to compare effects on pulmonary fibrosis and fibrosis-related indicators.RESULTS The MSC-MVs gradually migrated and homed to damaged lung tissues in the ARDS model mice.Treatment with MSC-MVs significantly reduced lung injury and pulmonary fibrosis scores.However,low expression of HGF(siHGF-MSC-MVs)significantly inhibited the effects of MSC-MVs(P<0.05).Compared with the ARDS pulmonary fibrosis group,the MSC-MVs group exhibited suppressed expression of type I collagen antigen,type III collagen antigen,and the proteins transforming growth factor-βandα-smooth muscle actin,whereas the siHGF-MVs group exhibited significantly increased expression of these proteins.In addition,pulmonary compliance and the pressure of oxygen/oxygen inhalation ratio were significantly lower in the MSC-MVs group,and the effects of the MSC-MVs were significantly inhibited by low HGF expression(all P<0.05).CONCLUSION MSC-MVs improved lung ventilation functions and inhibited pulmonary fibrosis in ARDS mice partly via HGF mRNA transfer.

Predictive value of diaphragm ultrasound for mechanical ventilation outcome in patients with acute exacerbation of chronic obstructive pulmonary disease

BACKGROUND Acute exacerbation of chronic obstructive pulmonary disease(AECOPD)is often combined with respiratory failure,which increases the patient's morbidity and mortality.Diaphragm ultrasound(DUS)has developed rapidly in the field of critical care in recent years.Studies with DUS monitoring diaphragm-related rapid shallow breathing index have demonstrated important results in guiding intensive care unit patients out of the ventilator.Early prediction of the indications for withdrawal of non-invasive ventilator and early evaluation of patients to avoid or reduce disease progression are very important.AIM To explore the predictive value of DUS indexes for non-invasive ventilation outcome in patients with AECOPD.METHODS Ninety-four patients with AECOPD who received mechanical ventilation in our hospital from January 2022 to December 2023 were retrospectively analyzed,and they were divided into a successful ventilation group(68 cases)and a failed ventilation group(26 cases)according to the outcome of ventilation.The clinical data of patients with successful and failed noninvasive ventilation were compared,and the independent predictors of noninvasive ventilation outcomes in AECOPD patients were identified by multivariate logistic regression analysis.RESULTS There were no significant differences in gender,age,body mass index,complications,systolic pressure,heart rate,mean arterial pressure,respiratory rate,oxygen saturation,partial pressure of oxygen,oxygenation index,or time of inspiration between patients with successful and failed mechanical ventilation(P>0.05).The patients with successful noninvasive ventilation had shorter hospital stays and lower partial pressure of carbon dioxide(PaCO_(2))than those with failed treatment,while potential of hydrogen(pH),diaphragm thickening fraction(DTF),diaphragm activity,and diaphragm movement time were significantly higher than those with failed treatment(P<0.05).pH[odds ratio(OR)=0.005,P<0.05],PaCO_(2)(OR=0.430,P<0.05),and DTF(OR=0.570,P<0.05)were identified to be independent factors influencing the outcome of mechanical ventilation in AECOPD patients.CONCLUSION The DUS index DTF can better predict the outcome of non-invasive ventilation in AECOPD patients.

Pulmonary fibroblast-specific delivery of siRNA exploiting exosomes-based nanoscaffolds for IPF treatment

Idiopathic pulmonary fibrosis(IPF)is a progressive pulmonary disease that leads to interstitial inflammation,lung damage,and eventually life-threatening complications.Among various pathologic factors,Smad4 is a pivotal molecule involved in the progression and exacerbation of IPF.It mediates nuclear transfer of Smad2/Smad3 complexes and initiates the transcription of fibrosis-promoting genes.Thus,the inhibition of Smad4 expression in pulmonary fibroblasts by small interfering RNAs(siRNAs)might be a promising therapeutic strategy for IPF.Herein,we engineered exosome membranes(EM)by cationic lipid(i.e.,DOTAP)to load siRNAs against Smad4(DOTAP/siSmad4@EM),and investigated their specific delivery to pulmonary fibroblasts for treating IPF in a mouse model via pulmonary administration.As reference nanoscaffolds,undecorated DOTAP/siSmad4 complexes(lipoplexes,consisting of cationic lipid DOTAP and siRNAs)and siSmad4-loaded lipid nanoparticles(DOTAP/siSmad4@lipo,consisting of lipoplexes fused with DPPC–Chol liposomes)were also prepared.The results showed that DOTAP/siSmad4@EM exhibited a higher cellular uptake and gene silencing efficacies in mouse pulmonary fibroblasts(viz.,MLg2908)as compared to the two reference nanoscaffolds.Furthermore,the outcomes of the in vivo experiments illustrated that DOTAP/siSmad4@EM could significantly down-regulate the Smad4 expression with augmented anti-fibrosis efficiency.Additionally,the DOTAP/siSmad4@EM conferred excellent biocompatibility with low cytokine levels in bronchoalveolar lavage fluid and proinflammatory responses in the pulmonary area.Taken together,the outcomes of our investigation imply that specific inhibition of Smad4 expression in pulmonary fibroblasts by pulmonary administrated DOTAP/siSmad4@EM is a promising therapeutic strategy for IPF,which could safely and effectively deliver siRNA drugs to the targeted site of action.

The diagnostic yield for computed tomography pulmonary angiography in patients with anticoagulation

BACKGROUND:Patients who present to the emergency department(ED)for suspected pulmonary embolism(PE)are often on active oral anticoagulation(AC).However,the diagnostic yield of computed tomography pulmonary angiography(CTPA)in screening for PE in patients who present on AC has not been well characterized.We aim to investigate the diagnostic yield of CTPA in diagnosing PE depending on AC status.METHODS:We reviewed and analyzed the electronic medical records of patients who underwent CTPA for PE at a university hospital ED from June 1,2019,to March 25,2022.Primary outcome was the incidence of PE on CTPA depending on baseline AC status and indication for AC.RESULTS:Of 2,846 patients,242 were on AC for a history of venous thromboembolism(VTE),210 were on AC for other indications,and 2,394 were not on AC.The incidence of PE on CTPA was significantly lower in patients on AC for other indications(5.7%)when compared to patients on AC for prior VTE(24.3%)and patients not on AC at presentation(9.8%)(P<0.001).In multivariable analysis among the whole cohort,AC was associated with a positive CTPA(odds ratio[OR]0.26,95%confidence interval[CI]:0.15-0.45,P<0.001).CONCLUSION:The incidence of PE among patients undergoing CTPA in the ED is lower in patients previously on AC for indications other than VTE when compared to those not on AC or those on AC for history of VTE.AC status and indication for AC may affect pre-test probability of a positive CTPA,and AC status therefore warrants consideration as part of future diagnostic algorithms among patients with suspected PE.

Hypoxia in the pulmonary vein increases pulmonary vascular resistance independently of oxygen in the pulmonary artery

Introduction:Hypoxic pulmonary vasoconstriction(HPV)can be a challenging clinical problem.It is not fully elucidated where in the circulation the regulation of resistance takes place.It is often referred to as if it is in the arteries,but we hypothesized that it is in the venous side of the pulmonary circulation.Methods:In an open thorax model,pigs were treated with a veno-venous extra corporeal membrane oxygenator to either oxygenate or deoxygenate blood passing through the pulmonary vessels.At the same time the lungs were ventilated with extreme variations of inspired air from 5%to 100%oxygen,making it possible to make combinations of high and low oxygen content through the pulmonary circulation.A flow probe was inserted around the main pulmonary artery and catheters in the pulmonary artery and in the left atrium were used for pressure monitoring and blood tests.Under different combinations of oxygenation,pulmonary vascular resistance(PVR)was calculated.Results:With unchanged level of oxygen in the pulmonary artery and reduced inspired oxygen fraction lowering oxygen tension from 29 to 6.7 kPa in the pulmonary vein,PVR was doubled.With more extreme hypoxia PVR suddenly decreased.Combinations with low oxygenation in the pulmonary artery did not systematic influence PVR if there was enough oxygen in the inspired air and in the pulmonary veins.Discussion:The impact of hypoxia occurs from the alveolar level and forward with the blood flow.The experiments indicated that the regulation of PVR is mediated from the venous side.

Treatment and Clinical Management of Chronic Thromboembolic Pulmonary Hypertension:An Update of Literature Review

Chronic thromboembolic pulmonary hypertension(CTEPH)is a chronic,progressive,debilitating,and life-threa-tening complication of pulmonary embolism(PE).Recent technological advances have permitted various treat-ment options for the treatment of CTEPH,including surgery,angioplasty,and medical treatment,depending on the location and characteristics of lesions.Pulmonary endarterectomy(PEA)is the treatment of choice for CTEPH,as it offers excellent long-term outcomes and a high probability of recovery.Moreover,various medical and interventional therapies are currently being developed for patients with inoperable CTEPH.This review mainly summarizes the current treatment approaches of CTEPH,offering more options for specialist physicians to,thus,better manage chronic thromboembolic syndromes.

Primary pulmonary meningioma and minute pulmonary meningothelial-like nodules: Rare pulmonary nodular lesions requiring more awareness in clinical practice

In this editorial,we comment on an article by Ruan et al published in a recent issue of the World Journal of Clinical Case.Pulmonary meningothelial proliferative lesions,including primary pulmonary meningiomas,minute pulmonary meningothelial-like nodules,and metastatic pulmonary meningiomas are rare pulmonary lesions.These lesions are difficult to differentiate from lung cancers based on clinical and imaging manifestations.Herein,we briefly introduce the clinical,imaging,and pathological characteristics of these lesions and discuss their pathogenesis to strengthen the current understanding of pulmonary meningothelial proliferative lesions in clinical diagnosis and therapy.

Oral bacteria-associated liver abscess in conjunction with pulmonary arteriovenous fistula:a case report

Pulmonary arteriovenous fistul a(PAVF)represents an abnormal direct connection between the pulmonary artery and vein,circumventing the alveolar capillary network.A right-to-left shunt in the lungs precluding proper gas exchange and reduces pulmonary capillary filtration.