Purpose:The aim was to synthesize quantitative and qualitative research that identified the most effective educational strategies for nurse-led inhaler technique(IT)education in Chronic Obstructive Pulmonary Disease(C...Purpose:The aim was to synthesize quantitative and qualitative research that identified the most effective educational strategies for nurse-led inhaler technique(IT)education in Chronic Obstructive Pulmonary Disease(COPD)patients,as perceived by patients,healthcare providers,and nurses.Methods:A systematic literature search in Embase,PubMed,Cochrane Library,Web of Science,and CINAHL from 2018 to 30 June 2024 was conducted.In total,327 articles were identified.The results of 14 studies that met the inclusion criteria were synthesized.Data were analyzed with des-criptive and semi-quantitative methods to yield summarizing findings on the effectiveness of different educational strate-gies.All investigations had assessed patient adherence to IT.Results:Data indicated that nurse-led IT teaching strategies are effective in promoting IT adherence and correctness in COPD patients utilizing the personalized Teach-Back method.However,studies in disease control and comparison of patient IT satisfaction and self-efficacy need further investigation.Conclusion:The results of this study may contribute to the understanding of the most effective educational strategies in nurse-led IT education for COPD patients.The synthesized findings can be used for the development of new educational interventions and assessment instruments for IT adherence.展开更多
Objective: To evaluate errors in the use of inhalation techniques in patients with chronic obstructive pulmonary disease(COPD), and to provide evidence for improving the effectiveness of drugs.Methods: A meta-analysis...Objective: To evaluate errors in the use of inhalation techniques in patients with chronic obstructive pulmonary disease(COPD), and to provide evidence for improving the effectiveness of drugs.Methods: A meta-analysis was performed after searching for literature at Pub Med, Embase, Web of Science, Cochrane Library, CINAHL, China National Knowledge Infrastructure(CNKI), Wan Fang, VIP, and Sion Med databases which were published from January 2011 to October 2020, addressing errors in the use of inhalation technologies for the treatment of COPD. After reviewing the literature, extracting per tinent information, and evaluating the risk of bias for the included studies, statistical analysis was performed using Stata 15.1.Results: Thir teen papers(12 in English and 1 in Chinese), representing 2527 patients, met the search criteria and were included in the meta-analysis. The results showed that the combined effect size of COPD patients making at least one operational error was 76%(95% CI: 0.69–0.83). The error rate varied with inhaler type;the combined effect size error for powered inhalers was 66%(95% CI: 0.57, 0.74), 67%(95% CI. 0.57, 0.77) for metered-dose inhalers(MDI), and 51%(95% CI: 0.38, 0.64) for soft mist inhalers(SMI).Conclusions: More than 75% of patients with COPD were unable to consistently use inhalers correctly, with the highest error rate for MDI. Therefore, health care providers must continue to educate patients on proper use of inhaler, ensuring their correct use and reducing the risk of acute COPD exacerbations.展开更多
Dry powder inhaler Liposomes were prepared to investigate the effectiveness of pulmonary delivery of Colchicine and Budesonide for Idiopathic Pulmonary fibrosis. Budesonide(BUD) and Colchicine(COL) liposomes were prep...Dry powder inhaler Liposomes were prepared to investigate the effectiveness of pulmonary delivery of Colchicine and Budesonide for Idiopathic Pulmonary fibrosis. Budesonide(BUD) and Colchicine(COL) liposomes were prepared by thin layer film hydration method(TFH) using 1,2-Dipalmitoyl-sn-glycero-3-phosphoglycerol sodium(DPPG), Hydrogenated Soyaphosphotidylcholine(HSPC), Soyaphosphatidylcholine(SPC), cholesterol(CHOL) and drug in different weight ratios. The optimum lipid composition for BUD(74.22 ± 0.97%) was DPPG:HSPC: CHOL(4:5:1) and for COL(50.94 ± 2.04%) was DPPG: SPC: CHOL(3:6:1). These compositions retained drug for a longer period of time so selected for further study. Liposomes were found to be spherical in shape with mean size below 100 nm. Liposomes lyophilized using Mannitol as carrier and cryoprotectant showed high entrapment efficiency(97.89-98.6%). The powder was dispersed through an Andersen cascade impactor to evaluate the performance of the aerosolized powder. It was found that prepared liposomal dry powder inhaler(DPIs) sustained the drug release up to 24 hours. Optimized Budesonide DPI Formulation B2(86.53 ± 1.9%), Colchicine DPI Formulation C2(90.54 ± 2.3 %) and BUD and COL DPI Combination M2(89.91 ± 1.8%, 91.23 ± 1.9%). Histopathological results, measurements of lung hydroxyproline content, Myeloperoxidase activity indicated that liposomal drypowder inhaler administration attenuates lung fibrosis induced by bleomycin. Long term stability studies indicated that lyophilised BUD and COL liposomes were stable for 6 months at(25 °C± 2 °C, 60% ± 5% RH) and refrigerated conditions(2-8 °C). These results supported that combination of budesonide and colchicine liposomal dry powder inhaler pulmonary drug delivery for treatment of idiopathic Pulmonary Fibrosis exhibits prolonged drug retention at targeted site and reduces the systemic exposure.展开更多
Idiopathic pulmonary fibrosis(IPF)is a serious and fatal pulmonary inflammatory disease with an increasing incidenceworldwide.The drugs nintedanib and pirfenidone,are listed as conditionally recommended drugs in the“...Idiopathic pulmonary fibrosis(IPF)is a serious and fatal pulmonary inflammatory disease with an increasing incidenceworldwide.The drugs nintedanib and pirfenidone,are listed as conditionally recommended drugs in the“Evidence-Based Guidelines for the Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis”.However,these two drugs have many adverse reactions in clinical application.Salvianolic acid B(Sal B),a water-soluble component of Salvia miltiorrhiza,could alleviate bleomycin-induced peroxidative stress damage,and prevent or delay the onset of IPF by regulating inflammatory factors and fibrotic cytokines during the disease’s progression.However,Sal B is poorly absorbed orally,and patient compliance is poor when administered intravenously.Therefore,there is an urgent need to find a new non-injection route of drug delivery.In this study,Sal B was used as model drug and l-leucine(LL)as excipient to prepare Sal B dry powder inhaler(Sal B-DPI)by spray drying method.Modern preparation evaluation methods were used to assess the quality of Sal B-DPI.Sal B-DPI is promising for the treatment of IPF,according to studies on pulmonary irritation evaluation,in vivo and in vitro pharmacodynamics,metabolomics,pharmacokinetics,and lung tissue distribution.展开更多
Dry powder inhalers are often formulated by attaching micronized drug particles onto carrier particles, which are generally lactose. In this study, commercially available lactose was air jet milled to produce unique s...Dry powder inhalers are often formulated by attaching micronized drug particles onto carrier particles, which are generally lactose. In this study, commercially available lactose was air jet milled to produce unique slab-like coarse carrier particles, which have larger and rougher surfaces compared to other commercially available lactose. Two key processing factors, i.e.,classifier speed and jet milling pressure, were systematically investigated. The largest fraction of slab-like particles in the resulting powder was obtained at a classifier speed of 3000 rpm.The slab-like coarse carrier particles are expected to exhibit superior performance than commercial lactose due to their unique surface properties.展开更多
Ciclesonide is a new corticosteroid currently in clinical development for the treatment of asthma by oral inhalation. The objectives of the present study were to develop ciclesonide dry powder inhalers （DPIs, 80 μg...Ciclesonide is a new corticosteroid currently in clinical development for the treatment of asthma by oral inhalation. The objectives of the present study were to develop ciclesonide dry powder inhalers （DPIs, 80 μg） and investigate the anti-asthmatic effect in animals. For preparing a ciclesonide capsule-type DPI, sphere-shaped lactose was used as a diluent carrier, mixed with micronized ciclesonide, and filled into a capsule, and then put into a dry powder inhaler for oral inhalation. The asthmatic model was established with guinea pigs, and the therapeutic efficacy of ciclesonide was performed on the asthmatic guinea pig model. Results showed that the pulmonary deposition ratio of ciclesonide DPIs was approximately 26% and their content uniformity met the requirements of China Pharmacopoeia. The established pathological model exhibited the typical features of asthma with a widened pulmonary alveolar interval, narrowed alveolar space and detached bronchial mucosal epithelium with topical necrosis, goblet cell hyperplasia, and inflammatory cell infiltration. After treating with ciclesonide, the impaired indicators in asthmatic guinea pigs were significantly recovered or alleviated, exhibiting decreased total cells, decreased eosinophils and a decreased IL-5 level while there was an increased IFN-γ level in the bronchoalveolar lavage fluid （BALF）. This study develops a new pulmonary ciclesonide delivery system for treating asthma, and proves the therapeutic efficacy in asthmatic guinea pigs.展开更多
Objective: Dual bronchodilation with long-acting muscarinic antagonist and long-acting β2-agonist combinations are available worldwide in COPD patients. However, the choice of agents remains under debate. We hypothes...Objective: Dual bronchodilation with long-acting muscarinic antagonist and long-acting β2-agonist combinations are available worldwide in COPD patients. However, the choice of agents remains under debate. We hypothesized that switching devices between dry powder and soft mist inhalers without a wash-out period to mimic clinical practice would improve clinical symptoms and lung function. The aim of this study was to examine the effects of switching between once-daily glycopyrronium/indacaterol (GLY/IND) or umeclidinium/vilanterol (UMEC/VI), dry powder inhalers, and tiotropium/olodaterol (TIO/OLO), a soft mist inhaler, in COPD patients. Methods: This was a prospective, open-label, 8-week, observational study with follow-up. Subjects included 57 COPD patients, who attended outpatient clinics at Shizuoka General Hospital for routine check-ups between February and December 2015, receiving GLY/IND (50/110 μg) or UMEC/VI (62.5/25 μg). After an 8-week run-in period, medications were switched to TIO/OLO (5/5 μg). Study outcomes included patient’s global rating (PGR), modified MRC (mMRC), COPD assessment test (CAT), and spirometric and forced oscillatory parameters after 8 weeks. PGR used in this study was a 7-point scale ranging from 1 to 7, with 4 in the middle. Patients who consented to switch from TIO/OLO to GLY/IND or UMEC/VI were followed-up thereafter. Results: In total, 53 patients completed the study (mean age, 75 years;48 males and 5 females;GOLD 1/2/3/4 = 19/27/6/1;mMRC 0/1/2/3/4 = 14/22/12/4/1;UMEC/VI 26, GLY/IND 27). PGR, mMRC, and CAT improved in 20 (38%), 9 (17%), and 15 patients (28%), respectively. Respiratory system resistance at 5 Hz (R5), 20 Hz (R20), and the difference between R5 and R20 (R5 - R20) significantly improved. In a follow-up of 16 patients after switching from TIO/OLO to UMEC/VI (9) or GLY/IND (7), PGR, mMRC, and CAT improved in 5 (31%), 3 (12%), and 4 patients (25%), respectively, and R20 significantly improved (p = 0.011). Conclusions: Switching dual bronchodilators between dry powder and soft mist inhalers improves symptoms and airway narrowing in some COPD patients.展开更多
Objective:To determine the most common mistakes made during the use of a metered-dose inhaler(MDI),and the effect of the repeated trainings performed with demonstration method by providing one-to-one feedback on these...Objective:To determine the most common mistakes made during the use of a metered-dose inhaler(MDI),and the effect of the repeated trainings performed with demonstration method by providing one-to-one feedback on these mistakes.Methods:This is a quasi-experimental study with a control group.A total of 100 chronic obstructive pulmonary disease(COPD)patients(50 in the control group and 50 in the experimental group)were included in the research.“Patient Information Form(PIF)”(to determine the descriptive characteristics of patients)through the face-to-face interview method,using“MDI Skill Assessment Form”(MDISAF)(it is composed of 10 skill steps about the use of MDI)through observation method was used.Patients in both the groups were asked to use MDI and their abilities regarding use of MDI were assessed.Then in the intervention group,usage of MDI was explained by a nurse via demonstration and placebo MDI.Trainings were repeated on days 1,3,and 5 as from hospitalization of the patient.In the intervention group,three methods were used in this study:“face-to-face training,”“one-to-one,”and“with feedbacks and repeated.”Routine training regarding use of MDI was given by the nurses in the clinic to patients in the control group.The use of an MDI was assessed using MDISAF before training and after the training on the first,third and fifth days of hospitalization.On the seventh day,the last measurement was performed.Percentage,chi square,and mean were used to assess the data.Results:After repetitive training with one-to-one feedback,several differences between the groups in favor of the experimental group were found in 7 of the 10 skill levels of the MDI.There was a significant difference after“training”between the groups in the third,fourth,fifth,sixth,seventh,eighth and ninth MDI steps in posttest measurement(P<0.05).Evaluating the skills of the groups to use MDI from pretest to posttest,it was determined that while the intervention group made less mistakes in steps in which mistakes were made mostly,the control group continued to make mistakes.Conclusions:Inhaler technique intervention with repeated,face to face,and one-to-one feedback trainings can significantly enhance the MDI techniques in COPD patients.The patients in the intervention group made less mistakes during MDI application and their application skills improved.It may be asser ted that the training provided to the intervention group was effective for using the device correctly,while the training provided in the clinic for the control group was inadequate.展开更多
Lung cancer is the leading cause of cancer-related deaths. Traditional chemotherapy causes serious toxicity due to the wide bodily distribution of these drugs. Curcumin is a potential anticancer agent but its low wate...Lung cancer is the leading cause of cancer-related deaths. Traditional chemotherapy causes serious toxicity due to the wide bodily distribution of these drugs. Curcumin is a potential anticancer agent but its low water solubility, poor bioavailability and rapid metabolism significantly limits clinical applications. Here we developed a liposomal curcumin dry powder inhaler(LCD) for inhalation treatment of primary lung cancer. LCDs were obtained from curcumin liposomes after freeze-drying. The LCDs had a mass mean aerodynamic diameter of 5.81 μm and a fine particle fraction of 46.71%, suitable for pulmonary delivery. The uptake of curcumin liposomes by human lung cancer A549 cells was markedly greater and faster than that of free curcumin. The high cytotoxicity on A549 cells and the low cytotoxicity of curcumin liposomes on normal human bronchial BEAS-2B epithelial cells yielded a high selection index partly due to increased cell apoptosis. Curcumin powders, LCDs and gemcitabine were directly sprayed into the lungs of rats with lung cancer through the trachea. LCDs showed higher anticancer effects than the other two medications with regard to pathology and the expression of many cancer-related markers including VEGF, malondialdehyde, TNF-α, caspase-3 and BCL-2. LCDs are a promising medication for inhalation treatment of lung cancer with high therapeutic efficiency.展开更多
Dry powder inhalers(DPIs) offer distinct advantages as a means of pulmonary drug delivery and have attracted much attention in the field of pharmaceutical science. DPIs commonly contain micronized drug particles which...Dry powder inhalers(DPIs) offer distinct advantages as a means of pulmonary drug delivery and have attracted much attention in the field of pharmaceutical science. DPIs commonly contain micronized drug particles which, because of their cohesiveness and strong propensity to aggregate, have poor aerosolization performance. Thus carriers with a larger particle size are added to address this problem. However, the performance of DPIs is profoundly influenced by the physical properties of the carrier, particularly their particle size, morphology/shape and surface roughness. Because these factors are interdependent, it is difficult to completely understand how they individually influence DPI performance.The purpose of this review is to summarize and illuminate how these factors affect drug–carrier interaction and influence the performance of DPIs.展开更多
Air flow and particle-particle/wall impacts are considered as two primary dispersion mechanisms for dry powder inhalers(DPIs).Hence,an understanding of these mechanisms is critical for the development of DPIs.In this ...Air flow and particle-particle/wall impacts are considered as two primary dispersion mechanisms for dry powder inhalers(DPIs).Hence,an understanding of these mechanisms is critical for the development of DPIs.In this study,a coupled DEM-CFD(discrete element method-computational fluid dynamics)is employed to investigate the influence of air flow on the dispersion performance of the carrier-based DPI formulations.A carrier-based agglomerate is initially formed and then dispersed in a uniformed air flow.It is found that air flow can drag API particles away from the carrier and those in the downstream air flow regions are prone to be dispersed.Furthermore,the influence of the air velocity and work of adhesion are also examined.It is shown that the dispersion number(i.e.,the number of API particles detached from the carrier)increases with increasing air velocity,and decreases with increasing the work of adhesion,indicating that the DPI performance is controlled by the balance of the removal and adhesive forces.It is also shown that the cumulative Weibull distribution function can be used to describe the DPI performance,which is governed by the ratio of the fluid drag force to the pull-off force.展开更多
Particle interactions play a significant role in controlling the performance of dry powder inhalers （DPIs）, which mainly arise through van der Waals potentials, electrostatic interactions, and capillary forces. Our ...Particle interactions play a significant role in controlling the performance of dry powder inhalers （DPIs）, which mainly arise through van der Waals potentials, electrostatic interactions, and capillary forces. Our aim is to investigate the influence of electrostatic charge on the performance of DPIs as a basis for improv- ing the formulation of the particle ingredients. The mixing process of carrier and active pharmaceutical ingredient （API） particles in a vibrating container is investigated using a discrete element method （DEM）. The number of APl particles attaching to the carrier particle （i.e., contact number） increases with increas- ing charge and decreases with increasing container size. The contact number decreases with increasing vibrational velocity amplitude and frequency. Moreover, a mechanism governed by the electrostatic force is proposed for the mixing process. This mechanism is different from that previously proposed for the mixing process governed by van der Waals forces, indicating that long-range and short-range adhesive forces can result in different mixing behaviours.展开更多
Asthma and chronic obstructive airway disease ,（COAD） are chronic inflammatory disorders of the airways which are usually associated with widespread airway obstruction that is often relieved by treatment. β2-adreno...Asthma and chronic obstructive airway disease ,（COAD） are chronic inflammatory disorders of the airways which are usually associated with widespread airway obstruction that is often relieved by treatment. β2-adrenoreceptor agonists and corticosteriods are the mainstay of the management of this disease. The preferred route of administration of these agents is by inhalation. This allows the drug to be delivered directly to the airway with more rapid relief and fewer side effects than systemic route. The main disadvantage of metered-dose inhaler （MDI） use is that the correct use requires good technique;展开更多
For patients with lung disease,dry powder inhalers(DPI)are profoundly beneficial.The current study introduces and develops a series of dry powder inhalers(DPIs).A capsule-based(size 0)active DPI was considered.The stu...For patients with lung disease,dry powder inhalers(DPI)are profoundly beneficial.The current study introduces and develops a series of dry powder inhalers(DPIs).A capsule-based(size 0)active DPI was considered.The study aims to investigate whether swirling flow and outlet capillary diameter(dc_out)affect the percentage of emitted doses(ED)released from the capsule.Spiral vanes were added to the capillary inlet to produce a swirling flow.Computational fluid dynamics(CFD)was applied to simulate the problem.The results were compared with previous in vitro and numerical studies to validate the results.Based on the derived results,the small swirl parameter(SP)enhances the secondary flow and recirculation zone.It increases the central jet flow,which increases the ED value by about 5–20%compared to no-swirl flow.However,as the airflow rate increases,the recirculation zone enlarges,vorticities become dominant,and asymmetrical flow patterns emerge.Consequently,ED%drops significantly(more than 50%).As d_(c_out)decreases,the vorticities around the outlet capillary become more potent,which is undesirable.Indeed,the emptying of the capsule does not happen ideally.The research provides a perspective on the device's design and DPI performance.展开更多
In recent years,the rising prevalence of respiratory diseases,coupled with advancements in biotechnology and pharmacology,has positioned inhalable formulations as a preferred method of drug administration.This approac...In recent years,the rising prevalence of respiratory diseases,coupled with advancements in biotechnology and pharmacology,has positioned inhalable formulations as a preferred method of drug administration.This approach enables direct and rapid delivery of medication to the lungs,maximizing therapeutic effects while minimizing dosage and potential side effects.In this review,we meticulously examined current literature and clinical trial databases to present a comprehensive overview of three key areas:(1)inhalation devices currently utilized in clinical settings;(2)the clinical applications of approved inhalable formulations;and(3)preclinical research on inhalable treatments targeting various lung conditions,including pulmonary infections,tuberculosis,lung cancer,pulmonary fibrosis,as well as systemic diseases like Parkinson’s disease.The objective was to delve into both foundational research and the clinical use of inhalable formulations within the pharmaceutical field,with the aim of fostering their broader adoption and guiding the development of inhalable therapies for a more comprehensive range of diseases.展开更多
Pulmonary diseases are emerging as one of the leading causes of mortality worldwide,intensifying the urgent need for effective therapeutic interventions.mRNA therapeutics have attracted significant attention due to th...Pulmonary diseases are emerging as one of the leading causes of mortality worldwide,intensifying the urgent need for effective therapeutic interventions.mRNA therapeutics have attracted significant attention due to their therapeutic potential and may represent a new treatment strategy for pulmonary diseases.Delivering mRNA to the lungs via inhalation offers advantages,such as increased local drug concentration and reduced systemic exposure,presenting significant potential to meet the clinical needs of pulmonary diseases.However,the delivery process faces great challenges due to the physicochemical properties of mRNA and the lung's defense mechanisms.This review summarizes recent advancements in mRNA therapeutics for pulmonary inhalation delivery,highlighting the challenges faced in mRNA drug delivery to the lungs.Furthermore,the carrier design for inhaled mRNA delivery and its applications in pulmonary diseases were comprehensively discussed.Finally,we clarify the challenges that inhaled mRNA therapy must overcome before widespread clinical use,aiming to provide more efficient and safe therapeutic options for future pulmonary disease treatments.展开更多
Background:Pulmonary fibrosis(PF)is a refractory disease with limited treatment options.This study investigates the potential anti-PF effects of the herbal formula Yiqi Huatan Sanjie(YQHTSJ)administered via nebulized ...Background:Pulmonary fibrosis(PF)is a refractory disease with limited treatment options.This study investigates the potential anti-PF effects of the herbal formula Yiqi Huatan Sanjie(YQHTSJ)administered via nebulized inhalation,exploring its underlying mechanisms.Methods:The anti-fibrotic properties of nebulized YQHTSJ were assessed using a bleomycin(BLM)-induced PF mouse model.RNA sequencing identified differentially expressed genes(DEGs),and subsequent gene enrichment analysis,along with transcription factor(TF)prediction,revealed YQHTSJ-regulated DEGs.Active components and targets of YQHTSJ were retrieved from the HERB database,leading to the identification of key TFs interacting with DEGs.Quercetin,a constituent of YQHTSJ,was evaluated for its effects on transforming growth factor-β1-induced myofibroblast activation and BLM-induced PF.The direct binding interaction between quercetin and the key TF Jun proto-oncogene(JUN)was confirmed through molecular docking studies and the cellular thermal shift assay(CETSA)experiments.Results:Nebulized YQHTSJ was found to significantly inhibit PF and inflammation in the mouse model.RNA sequencing identified 135 DEGs regulated by YQHTSJ,and 27 key TFs associated with these DEGs were predicted.Among YQHTSJ’s potential targets,41 were identified as TFs,with six-JUN,Fos proto-oncogene,MYC proto-oncogene,RELA proto-oncogene,nuclear factor kappa B subunit 1,and peroxisome proliferator activated receptor alpha-recognized as key TFs targeted by YQHTSJ.Molecular docking and CETSA experiments confirmed that quercetin directly targets JUN protein and inhibits its phosphorylation,thereby contributing to the suppression of myofibroblast activation and PF.Conclusion:The potential mechanisms of YQHTSJ and its component quercetin in combating PF may involve the regulation of critical TFs like JUN and the suppression of pathogenic gene expression.展开更多
Background:Inhalation exposure is the gold standard when assessing pulmonary tox-icity.However,it typically requires substantial amounts of test material.Intratracheal instillation is an alternative administration tec...Background:Inhalation exposure is the gold standard when assessing pulmonary tox-icity.However,it typically requires substantial amounts of test material.Intratracheal instillation is an alternative administration technique,where the test substance is suspended in a liquid vehicle and deposited into the lung via the trachea.Instillation requires minimal test material,delivers an exact dose deep into the lung,and is less labor-intensive than inhalation exposures.However,one shortcoming is that the pro-cedure may induce short-term inflammation.To minimize this,we tested different modifications of the technique to identify the potential for refinement.Methods:First,we tested whether previous findings of increased inflammation could be confirmed.Next,we tested whether instillation with a disposable 1 mL syringe with ball-tipped steel-needle(Disposable-syringe/steel-needle)induced less inflammation than the use of our standard set-up,a 250μL reusable glass syringe with a disposable plastic catheter(Glass-syringe/plastic-catheter).Finally,we tested if access to pelleted and liquid feed prior to instillation affected inflammation.We evaluated inflammation by neutrophil numbers in bronchoalveolar fluid 24 h post-exposure.Results:Vehicle-instilled mice showed a small increase in neutrophil numbers com-pared to untreated mice.Neutrophil numbers were slightly elevated in the groups in-stilled with Disposable-syringe/steel-needle;an interaction with feed type indicated that the increase in neutrophils was more pronounced in combination with feed pel-lets compared to liquid feed.We found no difference between the feed types when using the Glass-syringe/plastic-catheter combination.Conclusion:The Glass-syringe/plastic-catheter combination induced the least exposure-related inflammation,confirming this as a preferred instillation procedure.展开更多
Objective:To evaluate the efficacy of Sanhua essential oil inhalation as aromatherapy in patients with breast cancer-related depression.Methods:In total,144 patients with breast cancer-related depression who underwent...Objective:To evaluate the efficacy of Sanhua essential oil inhalation as aromatherapy in patients with breast cancer-related depression.Methods:In total,144 patients with breast cancer-related depression who underwent postoperative chemotherapy were recruited.The participants in the control group(n=52)were offered a placebo(sunflower oil)daily,whereas those in the essential oil group(n=52)were administered Sanhua essential oil.This study evaluated depression improvement,Hamilton Depression Scale score,scores of symptoms in traditional Chinese medicine(TCM),Pittsburgh Sleepiness Quotient Index score,incidence of nausea and vomiting,and signal changes on functional magnetic resonance imaging.Results:Depression improved by 48.1%and 21.2%in the essential oil and control groups,respectively(P=.010).The Hamilton Depression Scale score(P=.017),scores for symptoms in TCM(P=.002),and the incidence of nausea and vomiting in the acute and delayed phases were lower in the essential oil group than in the control group(nausea in the acute phase,P=.017;nausea in the delayed phase,P=.039;vomiting in the acute phase,P=.008;vomiting in the delayed phase,P=.081).The Pittsburgh Sleepiness Quotient Index score was lower in the essential oil group than in the control group(P=.005).Significant differences existed between the two groups in the left superior parietal gyrus,right precuneus,left dorsolateral superior frontal gyrus,and right precentral gyrus according to functional connectivity on functional magnetic resonance imaging.Conclusion:Inhalation of Sanhua essential oil alleviated depression in patients undergoing chemotherapy for breast cancer,improved sleep quality,relieved TCM symptoms,reduced nausea and vomiting,and regulated activities in the brain regions.展开更多
This study explores the clinical efficacy of budesonide combined with ambroxol inhalation therapy for neonatal pneumonia.A total of 68 neonatal pneumonia patients treated at Li County Hospital from January 2023 to Dec...This study explores the clinical efficacy of budesonide combined with ambroxol inhalation therapy for neonatal pneumonia.A total of 68 neonatal pneumonia patients treated at Li County Hospital from January 2023 to December 2024 were randomly divided into a monotherapy group and a combination group,with 34 patients in each.The monotherapy group received ambroxol inhalation therapy,while the combination group received budesonide inhalation therapy in addition to ambroxol.The recovery progress,blood gas analysis indicators,inflammatory response improvement,and overall clinical efficacy were compared between the two groups.Results showed that the combination group experienced a significantly shorter time for body temperature normalization(3.36±0.58 days vs.4.59±0.45 days),oxygen inhalation duration(4.89±0.57min vs.6.96±0.79min),disappearance of shortness of breath and cough(4.56±0.29 days vs.6.63±0.75 days),and resolution of lung wet rales(5.62±1.46 days vs.7.92±1.28 days)compared to the monotherapy group(P<0.05).Additionally,the total effective rate was significantly higher in the combination group(97.06%)than in the monotherapy group(73.52%)(P<0.05).Post-treatment,the combination group exhibited significantly better blood gas analysis and inflammatory response indicators(P<0.05).These findings suggest that budesonide combined with ambroxol inhalation therapy can effectively improve blood oxygen saturation,reduce inflammation,promote faster recovery,and enhance overall clinical efficacy,making it a reliable treatment option for neonatal pneumonia.展开更多
文摘Purpose:The aim was to synthesize quantitative and qualitative research that identified the most effective educational strategies for nurse-led inhaler technique(IT)education in Chronic Obstructive Pulmonary Disease(COPD)patients,as perceived by patients,healthcare providers,and nurses.Methods:A systematic literature search in Embase,PubMed,Cochrane Library,Web of Science,and CINAHL from 2018 to 30 June 2024 was conducted.In total,327 articles were identified.The results of 14 studies that met the inclusion criteria were synthesized.Data were analyzed with des-criptive and semi-quantitative methods to yield summarizing findings on the effectiveness of different educational strate-gies.All investigations had assessed patient adherence to IT.Results:Data indicated that nurse-led IT teaching strategies are effective in promoting IT adherence and correctness in COPD patients utilizing the personalized Teach-Back method.However,studies in disease control and comparison of patient IT satisfaction and self-efficacy need further investigation.Conclusion:The results of this study may contribute to the understanding of the most effective educational strategies in nurse-led IT education for COPD patients.The synthesized findings can be used for the development of new educational interventions and assessment instruments for IT adherence.
基金supported by Health Department of Sichuan Province(No.Chuan Gan Research-2021-219)National Natural Science Foundation of China(No.72004020)。
文摘Objective: To evaluate errors in the use of inhalation techniques in patients with chronic obstructive pulmonary disease(COPD), and to provide evidence for improving the effectiveness of drugs.Methods: A meta-analysis was performed after searching for literature at Pub Med, Embase, Web of Science, Cochrane Library, CINAHL, China National Knowledge Infrastructure(CNKI), Wan Fang, VIP, and Sion Med databases which were published from January 2011 to October 2020, addressing errors in the use of inhalation technologies for the treatment of COPD. After reviewing the literature, extracting per tinent information, and evaluating the risk of bias for the included studies, statistical analysis was performed using Stata 15.1.Results: Thir teen papers(12 in English and 1 in Chinese), representing 2527 patients, met the search criteria and were included in the meta-analysis. The results showed that the combined effect size of COPD patients making at least one operational error was 76%(95% CI: 0.69–0.83). The error rate varied with inhaler type;the combined effect size error for powered inhalers was 66%(95% CI: 0.57, 0.74), 67%(95% CI. 0.57, 0.77) for metered-dose inhalers(MDI), and 51%(95% CI: 0.38, 0.64) for soft mist inhalers(SMI).Conclusions: More than 75% of patients with COPD were unable to consistently use inhalers correctly, with the highest error rate for MDI. Therefore, health care providers must continue to educate patients on proper use of inhaler, ensuring their correct use and reducing the risk of acute COPD exacerbations.
文摘Dry powder inhaler Liposomes were prepared to investigate the effectiveness of pulmonary delivery of Colchicine and Budesonide for Idiopathic Pulmonary fibrosis. Budesonide(BUD) and Colchicine(COL) liposomes were prepared by thin layer film hydration method(TFH) using 1,2-Dipalmitoyl-sn-glycero-3-phosphoglycerol sodium(DPPG), Hydrogenated Soyaphosphotidylcholine(HSPC), Soyaphosphatidylcholine(SPC), cholesterol(CHOL) and drug in different weight ratios. The optimum lipid composition for BUD(74.22 ± 0.97%) was DPPG:HSPC: CHOL(4:5:1) and for COL(50.94 ± 2.04%) was DPPG: SPC: CHOL(3:6:1). These compositions retained drug for a longer period of time so selected for further study. Liposomes were found to be spherical in shape with mean size below 100 nm. Liposomes lyophilized using Mannitol as carrier and cryoprotectant showed high entrapment efficiency(97.89-98.6%). The powder was dispersed through an Andersen cascade impactor to evaluate the performance of the aerosolized powder. It was found that prepared liposomal dry powder inhaler(DPIs) sustained the drug release up to 24 hours. Optimized Budesonide DPI Formulation B2(86.53 ± 1.9%), Colchicine DPI Formulation C2(90.54 ± 2.3 %) and BUD and COL DPI Combination M2(89.91 ± 1.8%, 91.23 ± 1.9%). Histopathological results, measurements of lung hydroxyproline content, Myeloperoxidase activity indicated that liposomal drypowder inhaler administration attenuates lung fibrosis induced by bleomycin. Long term stability studies indicated that lyophilised BUD and COL liposomes were stable for 6 months at(25 °C± 2 °C, 60% ± 5% RH) and refrigerated conditions(2-8 °C). These results supported that combination of budesonide and colchicine liposomal dry powder inhaler pulmonary drug delivery for treatment of idiopathic Pulmonary Fibrosis exhibits prolonged drug retention at targeted site and reduces the systemic exposure.
基金supported by Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (No. ZYYCXTD-D-202002)Scientific Research Project of Tianjin Municipal Education Commission (No.2019KJ083)
文摘Idiopathic pulmonary fibrosis(IPF)is a serious and fatal pulmonary inflammatory disease with an increasing incidenceworldwide.The drugs nintedanib and pirfenidone,are listed as conditionally recommended drugs in the“Evidence-Based Guidelines for the Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis”.However,these two drugs have many adverse reactions in clinical application.Salvianolic acid B(Sal B),a water-soluble component of Salvia miltiorrhiza,could alleviate bleomycin-induced peroxidative stress damage,and prevent or delay the onset of IPF by regulating inflammatory factors and fibrotic cytokines during the disease’s progression.However,Sal B is poorly absorbed orally,and patient compliance is poor when administered intravenously.Therefore,there is an urgent need to find a new non-injection route of drug delivery.In this study,Sal B was used as model drug and l-leucine(LL)as excipient to prepare Sal B dry powder inhaler(Sal B-DPI)by spray drying method.Modern preparation evaluation methods were used to assess the quality of Sal B-DPI.Sal B-DPI is promising for the treatment of IPF,according to studies on pulmonary irritation evaluation,in vivo and in vitro pharmacodynamics,metabolomics,pharmacokinetics,and lung tissue distribution.
基金the funding support for this study from GEA-NUS PPRL (N-148-000-008-001)SERC Grant No. 102 169 0049 (R-148-000-157-305)partial support from the NSF through the NNIN program
文摘Dry powder inhalers are often formulated by attaching micronized drug particles onto carrier particles, which are generally lactose. In this study, commercially available lactose was air jet milled to produce unique slab-like coarse carrier particles, which have larger and rougher surfaces compared to other commercially available lactose. Two key processing factors, i.e.,classifier speed and jet milling pressure, were systematically investigated. The largest fraction of slab-like particles in the resulting powder was obtained at a classifier speed of 3000 rpm.The slab-like coarse carrier particles are expected to exhibit superior performance than commercial lactose due to their unique surface properties.
基金Tianjin Pharmaceuticals Research Organization Co.,Ltd,and in part by the Key Grant of Beijing Natural Science Foundation(Grant No.7091005)
文摘Ciclesonide is a new corticosteroid currently in clinical development for the treatment of asthma by oral inhalation. The objectives of the present study were to develop ciclesonide dry powder inhalers （DPIs, 80 μg） and investigate the anti-asthmatic effect in animals. For preparing a ciclesonide capsule-type DPI, sphere-shaped lactose was used as a diluent carrier, mixed with micronized ciclesonide, and filled into a capsule, and then put into a dry powder inhaler for oral inhalation. The asthmatic model was established with guinea pigs, and the therapeutic efficacy of ciclesonide was performed on the asthmatic guinea pig model. Results showed that the pulmonary deposition ratio of ciclesonide DPIs was approximately 26% and their content uniformity met the requirements of China Pharmacopoeia. The established pathological model exhibited the typical features of asthma with a widened pulmonary alveolar interval, narrowed alveolar space and detached bronchial mucosal epithelium with topical necrosis, goblet cell hyperplasia, and inflammatory cell infiltration. After treating with ciclesonide, the impaired indicators in asthmatic guinea pigs were significantly recovered or alleviated, exhibiting decreased total cells, decreased eosinophils and a decreased IL-5 level while there was an increased IFN-γ level in the bronchoalveolar lavage fluid （BALF）. This study develops a new pulmonary ciclesonide delivery system for treating asthma, and proves the therapeutic efficacy in asthmatic guinea pigs.
文摘Objective: Dual bronchodilation with long-acting muscarinic antagonist and long-acting β2-agonist combinations are available worldwide in COPD patients. However, the choice of agents remains under debate. We hypothesized that switching devices between dry powder and soft mist inhalers without a wash-out period to mimic clinical practice would improve clinical symptoms and lung function. The aim of this study was to examine the effects of switching between once-daily glycopyrronium/indacaterol (GLY/IND) or umeclidinium/vilanterol (UMEC/VI), dry powder inhalers, and tiotropium/olodaterol (TIO/OLO), a soft mist inhaler, in COPD patients. Methods: This was a prospective, open-label, 8-week, observational study with follow-up. Subjects included 57 COPD patients, who attended outpatient clinics at Shizuoka General Hospital for routine check-ups between February and December 2015, receiving GLY/IND (50/110 μg) or UMEC/VI (62.5/25 μg). After an 8-week run-in period, medications were switched to TIO/OLO (5/5 μg). Study outcomes included patient’s global rating (PGR), modified MRC (mMRC), COPD assessment test (CAT), and spirometric and forced oscillatory parameters after 8 weeks. PGR used in this study was a 7-point scale ranging from 1 to 7, with 4 in the middle. Patients who consented to switch from TIO/OLO to GLY/IND or UMEC/VI were followed-up thereafter. Results: In total, 53 patients completed the study (mean age, 75 years;48 males and 5 females;GOLD 1/2/3/4 = 19/27/6/1;mMRC 0/1/2/3/4 = 14/22/12/4/1;UMEC/VI 26, GLY/IND 27). PGR, mMRC, and CAT improved in 20 (38%), 9 (17%), and 15 patients (28%), respectively. Respiratory system resistance at 5 Hz (R5), 20 Hz (R20), and the difference between R5 and R20 (R5 - R20) significantly improved. In a follow-up of 16 patients after switching from TIO/OLO to UMEC/VI (9) or GLY/IND (7), PGR, mMRC, and CAT improved in 5 (31%), 3 (12%), and 4 patients (25%), respectively, and R20 significantly improved (p = 0.011). Conclusions: Switching dual bronchodilators between dry powder and soft mist inhalers improves symptoms and airway narrowing in some COPD patients.
文摘Objective:To determine the most common mistakes made during the use of a metered-dose inhaler(MDI),and the effect of the repeated trainings performed with demonstration method by providing one-to-one feedback on these mistakes.Methods:This is a quasi-experimental study with a control group.A total of 100 chronic obstructive pulmonary disease(COPD)patients(50 in the control group and 50 in the experimental group)were included in the research.“Patient Information Form(PIF)”(to determine the descriptive characteristics of patients)through the face-to-face interview method,using“MDI Skill Assessment Form”(MDISAF)(it is composed of 10 skill steps about the use of MDI)through observation method was used.Patients in both the groups were asked to use MDI and their abilities regarding use of MDI were assessed.Then in the intervention group,usage of MDI was explained by a nurse via demonstration and placebo MDI.Trainings were repeated on days 1,3,and 5 as from hospitalization of the patient.In the intervention group,three methods were used in this study:“face-to-face training,”“one-to-one,”and“with feedbacks and repeated.”Routine training regarding use of MDI was given by the nurses in the clinic to patients in the control group.The use of an MDI was assessed using MDISAF before training and after the training on the first,third and fifth days of hospitalization.On the seventh day,the last measurement was performed.Percentage,chi square,and mean were used to assess the data.Results:After repetitive training with one-to-one feedback,several differences between the groups in favor of the experimental group were found in 7 of the 10 skill levels of the MDI.There was a significant difference after“training”between the groups in the third,fourth,fifth,sixth,seventh,eighth and ninth MDI steps in posttest measurement(P<0.05).Evaluating the skills of the groups to use MDI from pretest to posttest,it was determined that while the intervention group made less mistakes in steps in which mistakes were made mostly,the control group continued to make mistakes.Conclusions:Inhaler technique intervention with repeated,face to face,and one-to-one feedback trainings can significantly enhance the MDI techniques in COPD patients.The patients in the intervention group made less mistakes during MDI application and their application skills improved.It may be asser ted that the training provided to the intervention group was effective for using the device correctly,while the training provided in the clinic for the control group was inadequate.
文摘Lung cancer is the leading cause of cancer-related deaths. Traditional chemotherapy causes serious toxicity due to the wide bodily distribution of these drugs. Curcumin is a potential anticancer agent but its low water solubility, poor bioavailability and rapid metabolism significantly limits clinical applications. Here we developed a liposomal curcumin dry powder inhaler(LCD) for inhalation treatment of primary lung cancer. LCDs were obtained from curcumin liposomes after freeze-drying. The LCDs had a mass mean aerodynamic diameter of 5.81 μm and a fine particle fraction of 46.71%, suitable for pulmonary delivery. The uptake of curcumin liposomes by human lung cancer A549 cells was markedly greater and faster than that of free curcumin. The high cytotoxicity on A549 cells and the low cytotoxicity of curcumin liposomes on normal human bronchial BEAS-2B epithelial cells yielded a high selection index partly due to increased cell apoptosis. Curcumin powders, LCDs and gemcitabine were directly sprayed into the lungs of rats with lung cancer through the trachea. LCDs showed higher anticancer effects than the other two medications with regard to pathology and the expression of many cancer-related markers including VEGF, malondialdehyde, TNF-α, caspase-3 and BCL-2. LCDs are a promising medication for inhalation treatment of lung cancer with high therapeutic efficiency.
基金supported by Pearl River S&T Nova Program of Guangzhou(2014J2200082)
文摘Dry powder inhalers(DPIs) offer distinct advantages as a means of pulmonary drug delivery and have attracted much attention in the field of pharmaceutical science. DPIs commonly contain micronized drug particles which, because of their cohesiveness and strong propensity to aggregate, have poor aerosolization performance. Thus carriers with a larger particle size are added to address this problem. However, the performance of DPIs is profoundly influenced by the physical properties of the carrier, particularly their particle size, morphology/shape and surface roughness. Because these factors are interdependent, it is difficult to completely understand how they individually influence DPI performance.The purpose of this review is to summarize and illuminate how these factors affect drug–carrier interaction and influence the performance of DPIs.
基金The financial support from the Chinese Scholarship Council(CSC)the School of Chemical Engineering at the University of Birmingham through the Li Siguang Scholarship Scheme is gratefully acknowledged by the first author.
文摘Air flow and particle-particle/wall impacts are considered as two primary dispersion mechanisms for dry powder inhalers(DPIs).Hence,an understanding of these mechanisms is critical for the development of DPIs.In this study,a coupled DEM-CFD(discrete element method-computational fluid dynamics)is employed to investigate the influence of air flow on the dispersion performance of the carrier-based DPI formulations.A carrier-based agglomerate is initially formed and then dispersed in a uniformed air flow.It is found that air flow can drag API particles away from the carrier and those in the downstream air flow regions are prone to be dispersed.Furthermore,the influence of the air velocity and work of adhesion are also examined.It is shown that the dispersion number(i.e.,the number of API particles detached from the carrier)increases with increasing air velocity,and decreases with increasing the work of adhesion,indicating that the DPI performance is controlled by the balance of the removal and adhesive forces.It is also shown that the cumulative Weibull distribution function can be used to describe the DPI performance,which is governed by the ratio of the fluid drag force to the pull-off force.
文摘Particle interactions play a significant role in controlling the performance of dry powder inhalers （DPIs）, which mainly arise through van der Waals potentials, electrostatic interactions, and capillary forces. Our aim is to investigate the influence of electrostatic charge on the performance of DPIs as a basis for improv- ing the formulation of the particle ingredients. The mixing process of carrier and active pharmaceutical ingredient （API） particles in a vibrating container is investigated using a discrete element method （DEM）. The number of APl particles attaching to the carrier particle （i.e., contact number） increases with increas- ing charge and decreases with increasing container size. The contact number decreases with increasing vibrational velocity amplitude and frequency. Moreover, a mechanism governed by the electrostatic force is proposed for the mixing process. This mechanism is different from that previously proposed for the mixing process governed by van der Waals forces, indicating that long-range and short-range adhesive forces can result in different mixing behaviours.
文摘Asthma and chronic obstructive airway disease ,（COAD） are chronic inflammatory disorders of the airways which are usually associated with widespread airway obstruction that is often relieved by treatment. β2-adrenoreceptor agonists and corticosteriods are the mainstay of the management of this disease. The preferred route of administration of these agents is by inhalation. This allows the drug to be delivered directly to the airway with more rapid relief and fewer side effects than systemic route. The main disadvantage of metered-dose inhaler （MDI） use is that the correct use requires good technique;
基金This work was supported the National Natural Science Foundation of China(grant No.12172146).
文摘For patients with lung disease,dry powder inhalers(DPI)are profoundly beneficial.The current study introduces and develops a series of dry powder inhalers(DPIs).A capsule-based(size 0)active DPI was considered.The study aims to investigate whether swirling flow and outlet capillary diameter(dc_out)affect the percentage of emitted doses(ED)released from the capsule.Spiral vanes were added to the capillary inlet to produce a swirling flow.Computational fluid dynamics(CFD)was applied to simulate the problem.The results were compared with previous in vitro and numerical studies to validate the results.Based on the derived results,the small swirl parameter(SP)enhances the secondary flow and recirculation zone.It increases the central jet flow,which increases the ED value by about 5–20%compared to no-swirl flow.However,as the airflow rate increases,the recirculation zone enlarges,vorticities become dominant,and asymmetrical flow patterns emerge.Consequently,ED%drops significantly(more than 50%).As d_(c_out)decreases,the vorticities around the outlet capillary become more potent,which is undesirable.Indeed,the emptying of the capsule does not happen ideally.The research provides a perspective on the device's design and DPI performance.
文摘In recent years,the rising prevalence of respiratory diseases,coupled with advancements in biotechnology and pharmacology,has positioned inhalable formulations as a preferred method of drug administration.This approach enables direct and rapid delivery of medication to the lungs,maximizing therapeutic effects while minimizing dosage and potential side effects.In this review,we meticulously examined current literature and clinical trial databases to present a comprehensive overview of three key areas:(1)inhalation devices currently utilized in clinical settings;(2)the clinical applications of approved inhalable formulations;and(3)preclinical research on inhalable treatments targeting various lung conditions,including pulmonary infections,tuberculosis,lung cancer,pulmonary fibrosis,as well as systemic diseases like Parkinson’s disease.The objective was to delve into both foundational research and the clinical use of inhalable formulations within the pharmaceutical field,with the aim of fostering their broader adoption and guiding the development of inhalable therapies for a more comprehensive range of diseases.
基金l support from the National Natural Science Foundation of China(Nos.22377110,82402749,U23A20531,82502540,and 22407119)Henan Province Fund for Cultivating Advantageous Disciplines(No.222301420019)+1 种基金The work was supported by the China Postdoctoral Science Foundation(No.2025M77290)The work was supported by the Postdoctoral Fellowship Program of CPSF(No.GZB20250666).Figures 1−4 were created with BioRender.
文摘Pulmonary diseases are emerging as one of the leading causes of mortality worldwide,intensifying the urgent need for effective therapeutic interventions.mRNA therapeutics have attracted significant attention due to their therapeutic potential and may represent a new treatment strategy for pulmonary diseases.Delivering mRNA to the lungs via inhalation offers advantages,such as increased local drug concentration and reduced systemic exposure,presenting significant potential to meet the clinical needs of pulmonary diseases.However,the delivery process faces great challenges due to the physicochemical properties of mRNA and the lung's defense mechanisms.This review summarizes recent advancements in mRNA therapeutics for pulmonary inhalation delivery,highlighting the challenges faced in mRNA drug delivery to the lungs.Furthermore,the carrier design for inhaled mRNA delivery and its applications in pulmonary diseases were comprehensively discussed.Finally,we clarify the challenges that inhaled mRNA therapy must overcome before widespread clinical use,aiming to provide more efficient and safe therapeutic options for future pulmonary disease treatments.
基金supported by the Guangdong Basic and Applied Basic Research Foundation under Grant(2023A1515011243)National Natural Science Foundation of China under Grant(82004141)+2 种基金Bao’an Traditional Chinese Medicine Development Foundation under Grant(2022KJCX-ZJZL-11)Science,Technology,and Innovation Commission of Shenzhen Municipality under Grant(JCYJ20190808160407500)Shenzhen Bao’an Traditional Chinese Medicine Hospital Research Program under Grant(BAZYY20220701).
文摘Background:Pulmonary fibrosis(PF)is a refractory disease with limited treatment options.This study investigates the potential anti-PF effects of the herbal formula Yiqi Huatan Sanjie(YQHTSJ)administered via nebulized inhalation,exploring its underlying mechanisms.Methods:The anti-fibrotic properties of nebulized YQHTSJ were assessed using a bleomycin(BLM)-induced PF mouse model.RNA sequencing identified differentially expressed genes(DEGs),and subsequent gene enrichment analysis,along with transcription factor(TF)prediction,revealed YQHTSJ-regulated DEGs.Active components and targets of YQHTSJ were retrieved from the HERB database,leading to the identification of key TFs interacting with DEGs.Quercetin,a constituent of YQHTSJ,was evaluated for its effects on transforming growth factor-β1-induced myofibroblast activation and BLM-induced PF.The direct binding interaction between quercetin and the key TF Jun proto-oncogene(JUN)was confirmed through molecular docking studies and the cellular thermal shift assay(CETSA)experiments.Results:Nebulized YQHTSJ was found to significantly inhibit PF and inflammation in the mouse model.RNA sequencing identified 135 DEGs regulated by YQHTSJ,and 27 key TFs associated with these DEGs were predicted.Among YQHTSJ’s potential targets,41 were identified as TFs,with six-JUN,Fos proto-oncogene,MYC proto-oncogene,RELA proto-oncogene,nuclear factor kappa B subunit 1,and peroxisome proliferator activated receptor alpha-recognized as key TFs targeted by YQHTSJ.Molecular docking and CETSA experiments confirmed that quercetin directly targets JUN protein and inhibits its phosphorylation,thereby contributing to the suppression of myofibroblast activation and PF.Conclusion:The potential mechanisms of YQHTSJ and its component quercetin in combating PF may involve the regulation of critical TFs like JUN and the suppression of pathogenic gene expression.
基金This work was supported by the Focused Research Effort on Chemicals in the Working Environment(FFIKA)from the Danish Government.
文摘Background:Inhalation exposure is the gold standard when assessing pulmonary tox-icity.However,it typically requires substantial amounts of test material.Intratracheal instillation is an alternative administration technique,where the test substance is suspended in a liquid vehicle and deposited into the lung via the trachea.Instillation requires minimal test material,delivers an exact dose deep into the lung,and is less labor-intensive than inhalation exposures.However,one shortcoming is that the pro-cedure may induce short-term inflammation.To minimize this,we tested different modifications of the technique to identify the potential for refinement.Methods:First,we tested whether previous findings of increased inflammation could be confirmed.Next,we tested whether instillation with a disposable 1 mL syringe with ball-tipped steel-needle(Disposable-syringe/steel-needle)induced less inflammation than the use of our standard set-up,a 250μL reusable glass syringe with a disposable plastic catheter(Glass-syringe/plastic-catheter).Finally,we tested if access to pelleted and liquid feed prior to instillation affected inflammation.We evaluated inflammation by neutrophil numbers in bronchoalveolar fluid 24 h post-exposure.Results:Vehicle-instilled mice showed a small increase in neutrophil numbers com-pared to untreated mice.Neutrophil numbers were slightly elevated in the groups in-stilled with Disposable-syringe/steel-needle;an interaction with feed type indicated that the increase in neutrophils was more pronounced in combination with feed pel-lets compared to liquid feed.We found no difference between the feed types when using the Glass-syringe/plastic-catheter combination.Conclusion:The Glass-syringe/plastic-catheter combination induced the least exposure-related inflammation,confirming this as a preferred instillation procedure.
基金supported by grants from the National Natural Science Foundation of China Youth Project(82104952)Shanghai Science and Technology Commission Medical Innovation Research Special Fund(21Y11923600,23Y11921600)+2 种基金Shanghai Municipal Health Commission Clinical Research Special Fund(202140172)Yueyang Hospital Translational Medicine Research Institute Level Fund(2024yyzh05)Yueyang Hospital Young Talent Training Project(RY411.07.02.04).
文摘Objective:To evaluate the efficacy of Sanhua essential oil inhalation as aromatherapy in patients with breast cancer-related depression.Methods:In total,144 patients with breast cancer-related depression who underwent postoperative chemotherapy were recruited.The participants in the control group(n=52)were offered a placebo(sunflower oil)daily,whereas those in the essential oil group(n=52)were administered Sanhua essential oil.This study evaluated depression improvement,Hamilton Depression Scale score,scores of symptoms in traditional Chinese medicine(TCM),Pittsburgh Sleepiness Quotient Index score,incidence of nausea and vomiting,and signal changes on functional magnetic resonance imaging.Results:Depression improved by 48.1%and 21.2%in the essential oil and control groups,respectively(P=.010).The Hamilton Depression Scale score(P=.017),scores for symptoms in TCM(P=.002),and the incidence of nausea and vomiting in the acute and delayed phases were lower in the essential oil group than in the control group(nausea in the acute phase,P=.017;nausea in the delayed phase,P=.039;vomiting in the acute phase,P=.008;vomiting in the delayed phase,P=.081).The Pittsburgh Sleepiness Quotient Index score was lower in the essential oil group than in the control group(P=.005).Significant differences existed between the two groups in the left superior parietal gyrus,right precuneus,left dorsolateral superior frontal gyrus,and right precentral gyrus according to functional connectivity on functional magnetic resonance imaging.Conclusion:Inhalation of Sanhua essential oil alleviated depression in patients undergoing chemotherapy for breast cancer,improved sleep quality,relieved TCM symptoms,reduced nausea and vomiting,and regulated activities in the brain regions.
文摘This study explores the clinical efficacy of budesonide combined with ambroxol inhalation therapy for neonatal pneumonia.A total of 68 neonatal pneumonia patients treated at Li County Hospital from January 2023 to December 2024 were randomly divided into a monotherapy group and a combination group,with 34 patients in each.The monotherapy group received ambroxol inhalation therapy,while the combination group received budesonide inhalation therapy in addition to ambroxol.The recovery progress,blood gas analysis indicators,inflammatory response improvement,and overall clinical efficacy were compared between the two groups.Results showed that the combination group experienced a significantly shorter time for body temperature normalization(3.36±0.58 days vs.4.59±0.45 days),oxygen inhalation duration(4.89±0.57min vs.6.96±0.79min),disappearance of shortness of breath and cough(4.56±0.29 days vs.6.63±0.75 days),and resolution of lung wet rales(5.62±1.46 days vs.7.92±1.28 days)compared to the monotherapy group(P<0.05).Additionally,the total effective rate was significantly higher in the combination group(97.06%)than in the monotherapy group(73.52%)(P<0.05).Post-treatment,the combination group exhibited significantly better blood gas analysis and inflammatory response indicators(P<0.05).These findings suggest that budesonide combined with ambroxol inhalation therapy can effectively improve blood oxygen saturation,reduce inflammation,promote faster recovery,and enhance overall clinical efficacy,making it a reliable treatment option for neonatal pneumonia.
