Insight into the efficacy and safety of pirfenidone: The treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis(IPF)has a poor prognosis if left untreated;therefore,early treatment with pirfenidone is crucial.Lei et al conducted a retrospective analysis to evaluate the effectiveness of early pirfenidone treatment on lung function in 113 patients with IPF.In addition to other research,pirfeni-done has demonstrated efficacy in patients at all stages of IPF once correct diagnosis has been made.In advanced IPF,we include the requirement for pirfenidone.Therefore,it is essential to choose an appropriate method of adminis-tration method,such as inhalation.This may circumvent the drawbacks of the high cost and possible adverse effects of this drug.

Microvesicles derived from mesenchymal stem cells: A promising therapeutic strategy for acute respiratory distress syndrome-related pulmonary fibrosis?

Pulmonary fibrosis significantly contributes to the pathogenesis of acute respiratory distress syndrome(ARDS),markedly increasing patient mortality.Despite the established anti-fibrotic effects of mesenchymal stem cells(MSCs),numerous challenges hinder their clinical application.A recent study demon-strated that microvesicles(MVs)from MSCs(MSC-MVs)could attenuate ARDS-related pulmonary fibrosis and enhance lung function via hepatocyte growth factor mRNA transcription.This discovery presents a promising strategy for managing ARDS-associated pulmonary fibrosis.This article initially examines the safety and efficacy of MSCs from both basic science and clinical perspectives,subsequently exploring the potential and obstacles of employing MSC-MVs as a novel therapeutic approach.Additionally,it provides perspectives on future research into the application of MSC-MVs in ARDS-associated pulmonary fi-brosis.

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.

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.

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.

Convergent evolution in high-altitude and marine mammals:Molecular adaptations to pulmonary fibrosis and hypoxia

High-altitude and marine mammals inhabit distinct ecosystems but share a common challenge:hypoxia.To survive in low-oxygen environments,these species have evolved similar phenotypic pulmonary adaptations,characterized by a high density of elastic fibers.In this study,we explored the molecular mechanisms underlying these adaptations,focusing on pulmonary fibrosis and hypoxia tolerance through comparative genomics and convergent evolution analyses.We observed significant expansions and contractions in certain gene families across both high-altitude and marine mammals,closely associated with processes involved in pulmonary fibrosis.Notably,members of the keratin gene family,such as KRT17 and KRT14,appear to be associated with the development of the dense elastic fiber phenotype observed in the lungs of hypoxia-tolerant mammals.Through selection pressure and amino acid substitution analyses,we identified multiple genes exhibiting convergent accelerated evolution,positive selection,and amino acid substitution in these species,associated with adaptation to hypoxic environments.Specifically,the convergent evolution of ZFP36L1,FN1,and NEDD9 was found to contribute to the high density of elastic fibers in the lungs of both high-altitude and marine mammals,facilitating their hypoxia tolerance.Additionally,we identified convergent amino acid substitutions and gene loss events associated with sperm development,differentiation,and spermatogenesis,such as amino acid substitutions in SLC26A3 and pseudogenization of CFAP47,as confirmed by PCR.These genetic alterations may be linked to changes in the reproductive capabilities of these animals.Overall,this study offers novel perspectives on the genetic and molecular adaptations of high-altitude and marine mammals to hypoxic environments,with a particular emphasis on pulmonary fibrosis.

Trigonelline mitigates bleomycin-induced idiopathic pulmonary fibrosis in mice

Objective:To evaluate the effect of trigonelline on bleomycin-induced idiopathic pulmonary fibrosis(IPF)and to explore its underlying mechanisms using network pharmacology.Methods:IPF was induced in C57BL/6 mice by a single intratracheal instillation of bleomycin(5 mg/kg).Trigonelline was administered at doses of 25,50,and 100 mg/kg/day orally from the 2nd day post-bleomycin induction up to the 14th day.In IPF-induced mice,lung coefficient,immune cell infiltration in bronchoalveolar lavage fluid,and oxidative stress were measured.Histological alterations in lung tissues were also assessed.Moreover,network pharmacology approach was conducted to reveal molecular interactions of bleomycin and trigonelline with targets of IPF.Results:Trigonelline treatment reduced bleomycin-induced oxidative stress and immune cell infiltration,and mitigated physiological changes in the lung tissues of mice.Moreover,trigonelline alleviated bleomycin-induced histological alterations in lung tissues.Network pharmacology analysis showed that bleomycin and trigonelline interacted with IPF targets,such as NFKB1,HDAC2,HIF1A,and TLR4.Conclusions:The interaction of trigonelline with key IPF targets and its ameliorative effects on lung damage and oxidative stress highlight its potential in treating IPF.It may be considered an antifibrotic agent for further clinical development.

Early pirfenidone treatment enhances lung function in idiopathic pulmonary fibrosis patients

This editorial comments on the study by Lei et al investigating the efficacy of early treatment with pirfenidone on the lung function of patients with idiopathic pulmonary fibrosis(IPF)published.This study evaluates the efficacy of early treatment with pirfenidone on lung function in patients with IPF.The early and advanced stages of IPF are defined,highlighting the drug's benefits.While prior research indicates pirfenidone's effectiveness in advanced IPF,this study focuses on its advantages in early stages.The study emphasizes the importance of computed tomography imaging alongside biochemical data and lung function tests for a comprehensive analysis of symptom relief.Results show that early intervention with pirfenidone significantly reduces disease progression and preserves lung function,underscoring its potential as a critical treatment strategy in early IPF.

Strengthening pharmacotherapy research for COVID-19-induced pulmonary fibrosis

The global spread of severe acute respiratory syndrome coronavirus 2 has resulted in a significant number of individuals developing pulmonary fibrosis(PF),an irreversible lung injury.This condition can manifest within a short inter-val following the onset of pneumonia symptoms,sometimes even within a few days.While lung transplantation is a potentially lifesaving procedure,its limited availability,high costs,intricate surgeries,and risk of immunological rejection present significant drawbacks.The optimal timing of medication administration for coronavirus disease 2019(COVID-19)-induced PF remains controversial.Despite this,it is crucial to explore pharmacotherapy interventions,involving early and preventative treatment as well as pharmacotherapy options for advanced-stage PF.Additionally,studies have demonstrated disparities in anti-fibrotic treatment based on race and gender factors.Genetic mutations may also impact therapeutic efficacy.Enhancing research efforts on pharmacotherapy interventions,while considering relevant pharmacological factors and optimizing the timing and dosage of medication administration,will lead to enhanced,personalized,and fair treatment for individuals impacted by COVID-19-related PF.These measures are crucial in lessening the burden of the disease on healthcare systems and improving patients'quality of life.

Mesenchymal stem cells-extracellular vesicles alleviate pulmonary fibrosis by regulating immunomodulators

BACKGROUND Pulmonary fibrosis(PF)is a chronic interstitial lung disease characterized by fibroblast proliferation and extracellular matrix formation,causing structural damage and lung failure.Stem cell therapy and mesenchymal stem cells-extracellular vesicles(MSC-EVs)offer new hope for PF treatment.AIM To investigate the therapeutic potential of MSC-EVs in alleviating fibrosis,oxidative stress,and immune inflammation in A549 cells and bleomycin(BLM)-induced mouse model.METHODS The effect of MSC-EVs on A549 cells was assessed by fibrosis markers[collagen I andα-smooth muscle actin(α-SMA),oxidative stress regulators[nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1),and inflammatory regu-lators[nuclear factor-kappaB(NF-κB)p65,interleukin(IL)-1β,and IL-2].Similarly,they were assessed in the lungs of mice where PF was induced by BLM after MSC-EV transfection.MSC-EVs ion PF mice were detected by pathological staining and western blot.Single-cell RNA sequencing was performed to investigate the effects of the MSC-EVs on gene expression profiles of macrophages after modeling in mice.RESULTS Transforming growth factor(TGF)-β1 enhanced fibrosis in A549 cells,significantly increasing collagen I andα-SMA levels.Notably,treatment with MSC-EVs demonstrated a remarkable alleviation of these effects.Similarly,the expression of oxidative stress regulators,such as Nrf2 and HO-1,along with inflammatory regulators,including NF-κB p65 and IL-1β,were mitigated by MSC-EV treatment.Furthermore,in a parallel manner,MSC-EVs exhibited a downregulatory impact on collagen deposition,oxidative stress injuries,and inflammatory-related cytokines in the lungs of mice with PF.Additionally,the mRNA sequencing results suggested that BLM may induce PF in mice by upregulating pulmonary collagen fiber deposition and triggering an immune inflammatory response.The findings collectively highlight the potential therapeutic efficacy of MSC-EVs in ameliorating fibrotic processes,oxidative stress,and inflammatory responses associated with PF.CONCLUSION MSC-EVs could ameliorate fibrosis in vitro and in vivo by downregulating collagen deposition,oxidative stress,and immune-inflammatory responses.

Timing impact on the initiation of pirfenidone therapy on idiopathic pulmonary fibrosis disease progression

In this editorial,we comment on the article by Lei et al,with a specific focus on the timing of the initiation of the antifibrotic agent pirfenidone(PFD)in the management of idiopathic pulmonary fibrosis(IPF)and its impact on lung function of IPF patients.PFD is an antifibrotic agent that is widely used in the management of IPF in both early and advanced stages.It inhibits various pathways and has antifibrotic,anti-inflammatory,and antioxidant properties.Despite dosage lowering,PFD slowed IPF progression and maintained functional capacity.The 6-min walk distance test indicated that patients tolerated adverse events well,and PFD significantly reduced the incidence of progression episodes and death.Even when a single disease-progression event occurred,continuing PFD treatment had benefits.

Effects of Qishi Shengjiang Guiyuan Granules on Inflammatory Response and T Lymphocyte Subsets in Peripheral Blood of Rats with GERD-Associated Idiopathic Pulmonary Fibrosis

[Objectives] To explore the effects of Qishi Shengjiang Guiyuan Granules on inflammatory response and T lymphocyte subsets in peripheral blood of rats with idiopathic pulmonary fibrosis (IFP) associated with gastroesophageal reflux disease (GERD).[Methods] Twenty-four SPF SD rats were randomly divided into control group, model group, Chinese medicine group and western medicine group, with 6 rats in each group. Except the control group, the other three groups were used to establish the rat model of GERD combined with IPF by injecting hydrochloric acid into the lower end of esophagus and inhaling diluted bleomycin (5 mg/kg). Rats in the Chinese medicine group (14 g/kg), rats in the western medicine group (4.17 g/kg), rats in the control group and the model group were given the same volume of saline by gavage for 14 d. Morphological and pathological changes of esophageal and lung tissues were observed under light microscope, and T lymphocyte subsets (CD_(3)^(+), CD_(4)^(+), CD_(8)^(+)) and the ratio of CD_(4)^(+)/CD_(8)^(+) in peripheral blood were detected by flow cytometry.[Results] Compared with the control group, the pulmonary tissue of the model group showed that the pulmonary interstitium was obviously thickened, the alveoli were mutually fused, the structure was obviously destroyed, the original alveolar structure was disappeared, the inflammatory cell infiltration was around the pulmonary capillaries and the alveolar space, and the basal cell hyperplasia and inflammatory cell infiltration were at the lower end of the esophagus. Compared with the model group, the degree of inflammatory cell infiltration and lung tissue damage in the Chinese medicine group and the western medicine group was significantly reduced, the inflammatory infiltration in the lower esophagus was significantly reduced, and the cell proliferation was reduced. Compared with the control group, the CD_(3)^(+), CD_(4)^(+), CD_(8)^(+), CD_(4)^(+)/CD_(8)^(+) in the peripheral blood of the rats in the model group, the Chinese medicine group and the western medicine group decreased ( P <0.01). Compared with the model group, CD_(3)^(+), CD_(4)^(+), and CD_(4)^(+)/CD_(8)^(+) increased ( P >0.05, P >0.05, P <0.01), CD_(8)^(+) decreased ( P >0.05). Compared with the Chinese medicine group, CD_(3)^(+), CD_(4)^(+), and CD_(4)^(+)/CD_(8)^(+) increased ( P >0.05, P >0.05, P <0.01) and CD_(8)^(+) decreased ( P >0.05) in the western medicine group.[Conclusions] Qishi Shengjiang Guiyuan Granules can effectively improve the inflammation of the lower esophagus and lung tissues of the pulmonary fibrosis rats with GERD and IFP, and regulate the number of T lymphocyte subsets CD_(3)^(+), CD_(4)^(+), CD_(8)^(+) cells and CD_(4)^(+)/CD_(8)^(+) ratio in peripheral blood.

Prognosis of Connective Tissue Disease Related Interstitial Lung Disease after Initiation of Long-Term Oxygen Therapy: Comparison with Idiopathic Pulmonary Fibrosis

Objective: The studies of long-term oxygen therapy (LTOT) for patents with connective tissue disease-related interstitial lung disease (CTD-ILD) are limited. This study aimed to evaluate the prognosis of CTD-ILD patients following the initiation of LTOT, compared to those with idiopathic pulmonary fibrosis (IPF). Methods: We conducted a retrospective analysis of patients with CTD-ILD and IPF who were introduced to LTOT between January 2014 and December 2020. Results: The study included 24 patients with CTD-ILD and 55 patients with IPF. At the initiation of LTOT, female gender, never-smoking history, higher body mass index (BMI), higher lactate dehydrogenase (LDH) level, lower pulmonary Surfactant Protein-D (SP-D) level and lower Gender-Age-Physiology (GAP) scores were more common in the CTD-ILD group (all Conclusion: Although patients with CTD-ILD had longer overall survival than those with IPF, there was no significant difference in prognosis after the initiation of LTOT between the two groups. Early intervention including treatment and management will be needed in CTD-ILD as in IPF.

Investigating the mechanism of action of Bu-Yang-Huan-Wu decoction in treating bleomycin-Induced pulmonary fibrosis through the epithelial-mesenchymal transition pathway

Background:To explore the effects and mechanisms of Bu-Yang-Huan-Wu Decoction on pulmonary fibrosis in mice.Methods:Forty-five C57BL/6J mice were randomly divided into three groups:Control,Model,and Bu-Yang-Huan-Wu Decoction.Pulmonary fibrosis was elicited in mice through a solitary intratracheal administration of 2.5 mg/kg bleomycin.For the control group,mice were given a solitary intratracheal administration of a comparable volume of PBS.Treatment began on the first day after the successful model establishment and lasted for 21 days.The survival rate and body weight of the mice were recorded daily,and on the 22nd day,bronchoalveolar lavage fluid was collected to determine total cells and total protein.The wet/dry weight ratio of lung tissue and hydroxyproline were measured.Lung tissue pathology was observed using hematoxylin and eosin staining and Masson staining.The mRNA expression of epithelial-mesenchymal transition-related proteins(E-cadherin and vimentin)was detected by RT-qPCR,and their protein expression was analyzed by western blot.Results:Compared to the model group,the Bu-Yang-Huan-Wu Decoction treatment notably enhanced both the survival rate and body weight in pulmonary fibrosis mice,significantly reduced lung tissue wet/dry weight ratio,total cells,and protein in bronchoalveolar lavage fluid,and hydroxyproline content.The pathological morphology of lung tissue was significantly improved,with increased expression of the epithelial cell marker E-cadherin mRNA and protein,and decreased expression of the mesenchymal cell marker vimentin mRNA and protein.Conclusion:Bu-Yang-Huan-Wu Decoction can improve the degree of bleomycin-induced pulmonary fibrosis in mice by inhibiting epithelial-mesenchymal transition.

Subretinal fibrosis secondary to neovascular age-related macular degeneration:mechanisms and potential therapeutic targets

Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.

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.

Diagnostic utility of microRNA profiles in cavitatory and noncavitatory pulmonary tuberculosis:Research protocol

BACKGROUND Tuberculosis(TB)is a common infection causing huge morbidity and mortality to mankind.The analytical methods used in diagnosing TB are not sensitive in paucibacillary infections and also require trained technical personnel.MicroRNAs are stable in serum and other body fluids,and hold great potential in the diagnosis of TB.AIM To analyze the dysregulated microRNA profiles among patients with cavitatory and non-cavitatory pulmonary TB.METHODS The prospective study will be conducted in a tertiary care center in India.Adult patients with newly diagnosed pulmonary TB will be included.There will be two groups:Patients with sputum positive pulmonary TB with cavity and without cavity(group1),and apparently healthy individuals(group 2).The participants will undergo sputum examination,Xpert Mycobacterium TB complex/resistance to rifampin(Mtb/RIF)assay,chest X-ray,and blood investigations and serum microRNA detection.Ethics approval has been obtained.Written informed consent will be obtained.Appropriate statistical analyses will be used.RESULTS MicroRNAs will be correlated with sputum positivity,Xpert Mtb/RIF assay,radiological involvement,inflammatory markers,and course of the disease among cases and controls.CONCLUSION MicroRNAs could serve as potential diagnostic biomarkers in diagnostically challenging TB patients.

Hotspots and trends in stem cell therapy for liver fibrosis and cirrhosis: A bibliometric analysis

BACKGROUND Liver fibrosis and cirrhosis are global medical challenges that require safe and effective treatments.In the past two decades,there has been a surge in research on stem cell therapy for liver fibrosis and cirrhosis.This study aimed to conduct a comprehensive analysis of the research hotspots and trends in this field through bibliometrics.sters was conducted.RESULTS As of September 20,2024,a total of 1935 documents were retrieved dating from 2004 to 2024,with 1186 strongly relevant publications obtained after screening.China,the United States,and Japan were the major contributors in this field.Cairo University,Zhejiang University and Yamaguchi University were the major institution in this field.The journal Stem Cell Research&Therapy published the most papers.There were 686 authors,with Shuji Terai,Isao Sakaida,Soon Koo Baik,and Lanjuan Li publishing the most papers.The research focused on alcoholic cirrhosis and nonalcoholic fatty liver disease.The emerging areas of interest were extracellular vesicles,exosomes,and their enriched microRNAs.The field is experiencing rapid growth due to the changing research trends and increasing literature.CONCLUSION These findings provide a thorough overview of stem cell therapy in the field of liver fibrosis and cirrhosis.

Rapid improvement in postpartum pulmonary hypertension associated with hereditary hemorrhagic telangiectasia: A case report and review of literature

BACKGROUND Postpartum pulmonary arterial hypertension(PAH)complicated with hereditary hemorrhagic telangiectasia(HHT)is a rare condition.Diagnosing and treating PAH in patients with HHT can be challenging.To the best of our knowledge,no previous reports have investigated the efficacy of pulmonary vasodilators in improving hemodynamics in postpartum patients with this disease.CASE SUMMARY In this paper,we report a postpartum case of HHT combined with PAH,pre-senting with worsening dyspnea.Genetic testing revealed that the patient carried a heterozygous variant of activin receptor-like kinase 1.The patient received various treatments,including diuretics,anticoagulants,sildenafil,macitentan,inhalation of nitric oxide,and iloprost.Changes in PaO2/FiO2,pulmonary artery systolic pressure as assessed by echocardiography,and N-terminus pro-brain natriuretic peptide levels suggested that,except for iloprost inhalation,the other treatments appeared to have limited efficacy.CONCLUSION To our knowledge,this is the first report on efficacy of pulmonary vasodilators in postpartum patients with HHT and PAH.