According to modern research,the pathogenesis of asthma mainly includes airway inflammation,airway hyperresponsiveness,airway remodeling,etc.Airway remodeling is the key factor that leads to the progress of asthma,and...According to modern research,the pathogenesis of asthma mainly includes airway inflammation,airway hyperresponsiveness,airway remodeling,etc.Airway remodeling is the key factor that leads to the progress of asthma,and it is also the main factor that leads to airway hyperresponsiveness and irreversible airflow restriction.Traditional Chinese medicine believes that"phlegm and blood stasis"block the airway and narrow the lumen is the most important factor in the treatment of asthma.展开更多
Objective:Use data mining techniques to explore the rule of Chinese medicine used for airway remodeling.Methods:Search the literature on Chinese medicine use for airway remodeling in the past 20 years.With the help of...Objective:Use data mining techniques to explore the rule of Chinese medicine used for airway remodeling.Methods:Search the literature on Chinese medicine use for airway remodeling in the past 20 years.With the help of WPS Office Excel 11.1,IBM SPSS Statistics 23.0 and SPSS Modeler 18.0 software,prescriptions were analyzed for the frequency of drug use,the four natures,the five flavours and the channel tropism,cluster analysis and association analysis of high-frequency drugs.Results:There were 58 Chinese medicine prescriptions for airway remodeling be found,involving 105 Chinese medicines,the most frequent channel tropism were spleen,stomach,lung,large intestine,liver and gallbladder,the most frequent use of the five flavors was sour,sweet and pungent,the highest frequency of the four natures was cold and hot,cluster analysis yielded eight drug aggregation groups,and association rule analysis yielded five groups of high-frequency drug pairs.Conclusion:The main TCM treatments for airway remodeling are expelling phlegm,relieving cough,asthma calming,expelling blood stasis and deficiency tonifying.The results of this study can provide ideas for compounding and drug selection for subsequent studies.展开更多
In order to investigate the effect of nuclear factor κB (NF κB) on airway remodeling in asthmatic rats, 18 Wistar rats were divided into three groups: asthmatic group; pyrrolidine dithiocarbamate (PDTC) group, in wh...In order to investigate the effect of nuclear factor κB (NF κB) on airway remodeling in asthmatic rats, 18 Wistar rats were divided into three groups: asthmatic group; pyrrolidine dithiocarbamate (PDTC) group, in which rats were injected intraperitoneally with NF κB specific inhibitor PDTC (100 mg/kg) before ovalbumin (OVA) challenge; control group. The NF κB activity and the expression of inhibitory protein κBα (I κBα) in airway were detected by electrophoretic mobility shift assay (EMSA), Western blot and immunohistochemistry respectively. The infiltration of inflammatory cells, the number of Goblet cells, the area of collagen and smooth muscle in airway were measured by means of image analysis system. The results showed that with the up regulation of airway NF κB activity in asthmatic group, the number of goblet cells (3.08±0.86/100 μm basement membrane (BM)), the area of collagen (24.71±4.24 μm 2/μm BM) and smooth muscle (13.81±2.11 μm 2/μm BM) in airway were significantly increased ( P <0.05) as compared with control group (0.14±0.05/100 μm BM, 14.31 ±3.16 μm 2/μm BM and 7.67±2.35 μm 2/μm BM respectively) and PDTC group (0.33±0.14/100 μm BM, 18.16±2.85 μm 2/μm BM and 8.95±2.16 μm 2/μm BM respectively). However, there was no significant difference between PDTC group and control group ( P >0.05). It was concluded that the activity of NF κB is increased in airway of asthmatic rats. Inhibition of NF κB activation can attenuate constructional changes in asthma airway, suggesting NF κB may contribute to asthmatic airway remodeling.展开更多
Objective:To study the effect of adjuvant N-acetylcysteine (NAC) effervescent tablets therapy on cardiopulmonary function and airway remodeling in patients with stable chronic obstructive pulmonary disease (COPD).Meth...Objective:To study the effect of adjuvant N-acetylcysteine (NAC) effervescent tablets therapy on cardiopulmonary function and airway remodeling in patients with stable chronic obstructive pulmonary disease (COPD).Methods: Patients with stable COPD treated in Zigong Third People's Hospital and West China Hospital, Sichuan University between May 2014 and October 2016 were selected and randomly divided into two groups, NAC group received N-acetylcysteine effervescent tablets combined with routine treatment, and control group received routine treatment. Before treatment as well as 2 weeks and 4 weeks after treatment, oxidative stress indexes and airway remodeling indexes in serum as well as inflammatory response indexes in peripheral blood were determined.Results: MDA, PC, 8-OHdG, MMP2, MMP3 and MMP9 contents in serum as well as NLRP3, ASC, p38MAPK and TREM-1 mRNA expression levels in peripheral blood mononuclear cells of both groups of patients after treatment were significantly lower than those before treatment while TAC levels as well as TIMP1 and TIMP2 contents in serum were significantly higher than those before treatment, and MDA, PC, 8-OHdG, MMP2, MMP3 and MMP9 contents in serum a well as NLRP3, ASC, p38MAPK and TREM-1 mRNA expression levels in peripheral blood mononuclear cells of NAC group after treatment were significantly lower than those of control group while TAC levels as well as TIMP1 and TIMP2 contents in serum were significantly higher than those of control group.Conclusion:Adjuvant NAC effervescent tablets treatment of stable COPD can improve the effect of oxidative stress and inflammatory response on cardiopulmonary function, and inhibit the airway remodeling caused by protease activation.展开更多
Objective:To study the influence of budesonide and salbutamol atomization inhalation on Th17/Treg balance in patients with bronchial asthma and its correlation with airway remodeling.Methods:A total of 90 patients wit...Objective:To study the influence of budesonide and salbutamol atomization inhalation on Th17/Treg balance in patients with bronchial asthma and its correlation with airway remodeling.Methods:A total of 90 patients with bronchial asthma who received systemic treatment in our hospital between July 2013 and April 2016 were divided into control group (n=45) and observation group (n=45) according to random number table. Patients in the control group were treated with salbutamol atomization inhalation alone while those in observation group were treated with budesonide and salbutamol atomization inhalation. The Th17/Treg ratio in peripheral blood as well as serum contents of airway remodeling-related indicators was compared between two groups before and after treatment. The correlation between Th17/Treg balance and airway remodeling in patients with bronchial asthma was detected by Pearson test. Results:Before treatment, the differences in peripheral blood Th17/Treg ratio as well as serum contents of inflammatory mediators, growth factor indexes and collagen metabolism indexes were not statistically significant between two groups of patients. After treatment, peripheral blood Th17/Treg ratio in observation group was lower than that in control group, serum CRP, IL-8, IL-13 and TNF- contents in observation group were lower than those in control group, serum PDGF-BB, b-FGF and VEGF contents in observation group were lower than those in control group, and serum HA, PCⅢ and LN contents in observation group were lower than those in control group. The Th17/Treg ratio in patients with bronchial asthma after treatment was positively correlated with the levels of airway remodeling-related indexes.Conclusion:Budesonide combined with salbutamol atomization inhalation can optimize the Th17/Treg balance in patients with bronchial asthma, and Th17/Treg is directly correlated to the degree of airway remodeling.展开更多
Objective: To observe the expression of proto-oncogenes in the process of airway remodeling in asthma. Methods: Guinea pig was used as an asthma model challenged by ovoglobulin. Dot-blot, Northern-blot molecular hybri...Objective: To observe the expression of proto-oncogenes in the process of airway remodeling in asthma. Methods: Guinea pig was used as an asthma model challenged by ovoglobulin. Dot-blot, Northern-blot molecular hybridization and immunohistochemistry techniques were used to detect the expression of c-fos, c-myc, c-jun and c-sis. Results: Expression of c-fos and c-myc mRNA could not be detected or detected at very low level in the control group. There were greatly increased expression of c-fos and c-myc mRNA after guinea pigs were challenged by ovoglobulin. Thirty minutes after the challenge, the expression of c-fos and c-myc mRNA reached to the peak and returned to normal level 4 h after the challenge. Immunohistochemistry studies showed that Fos, Myc, Jun and Sis expressed at low level in control group and increased after ovoglobulin stimulation. Immunohistochemically positive cells laid in the plasma of airway epithelium, in cell nucleus of bronchial epithelium and in the inflammatory cells.展开更多
Objective: To explore the effect of Corbrin Capsule combined with routine western medicine on the airway remodeling process in patients with stable COPD. Methods: A total of 120 patients with stable COPD who were trea...Objective: To explore the effect of Corbrin Capsule combined with routine western medicine on the airway remodeling process in patients with stable COPD. Methods: A total of 120 patients with stable COPD who were treated in the hospital between May 2014 and December 2016 were collected and divided into control group and observation group according to the random number table method, 60 cases in each group. The control group received routine western medicine treatment, and the observation group received Corbrin Capsule combined with routine western medicine treatment. The differences in serum levels of inflammatory factors, growth factors and fibrosis indexes were compared between the two groups before and after treatment. Results: Before treatment, difference in serum levels of inflammatory factors, growth factors and fibrosis indexes were not statistically significant between the two groups of patients. After 8 weeks of treatment, serum IL-2, IL-4, IL-8, IL-18, VEGF, b-FGF, NGF, LN, HA, PⅢNP and C-Ⅳ levels of both groups of patients were significantly lower than those before treatment, and serum IL-2, IL-4, IL-8, IL-18, VEGF, b-FGF, NGF, LN, HA, PⅢNP and C-Ⅳ levels of observation group were lower than those of control group. Conclusion: Corbrin Capsule combined with routine western medicine treatment can effectively inhibit the fibrosis process in patients with stable COPD.展开更多
Objective: To study the effect of intermittent anaerobic exercise combined with inhalant therapy on airway remodeling and inflammatory response in children with asthma. Methods:A total of 92 children who were diagnose...Objective: To study the effect of intermittent anaerobic exercise combined with inhalant therapy on airway remodeling and inflammatory response in children with asthma. Methods:A total of 92 children who were diagnosed with bronchial asthma in Zigong Third People's Hospital between June 2015 and February 2017 were selected as the research subjects and randomly divided into exercise group and control group who received intermittent anaerobic exercise combined with inhalant therapy and regular inhalant therapy respectively. Results:4 weeks and 8 weeks after intervention, serum MMP2, MMP3, MMP9, ADAM33,TGF-β1, Smad3, CTGF, PINP, PIIINP, IL-4, IL-9, IL-21, TNF-α and hs-CRP levels of both groups of patients were significantly lower than those before intervention while TIMP1 levels were significantly higher than those before intervention, and serum MMP2, MMP3, MMP9, ADAM33,TGF-β1, Smad3, CTGF, PINP, PIIINP, IL-4, IL-9, IL-21, TNF-α and hs-CRP levels of exercise group were significantly lower than those of control group while TIMP1 levels were significantly higher than those of control group. Conclusion: Intermittent anaerobic exercise combined with inhalant therapy can improve airway remodeling and inflammatory response in children with asthma.展开更多
Objective:To study the effect of pediatric asthma complicated by respiratory virus infection on airway remodeling and inflammation.Methods:A total of 41 children with asthma complicated by respiratory virus infection ...Objective:To study the effect of pediatric asthma complicated by respiratory virus infection on airway remodeling and inflammation.Methods:A total of 41 children with asthma complicated by respiratory virus infection who were treated in our hospital between May 2012 and March 2016 were collected as observation group, and 50 children with asthma alone who were treated in our hospital during the same period were selected as control group. High-resolution CT was used to determine the right upper lobe apical segment (RB1) and the left lower lobe posterior basal segment (LB10) airway remodeling parameters of two groups of patients, and serum airway remodeling index and inflammatory factor contents were detected. Results: LA, WA and TA levels of RB1 and LB10 of observation group were significantly lower than those of control group, serum airway remodeling indexes TGF-β1, Smad3, PⅠNP and PⅢNP contents were higher than those of control group, serum inflammation indexes IL-4, IL-5 and TNF-α contents were higher than those of control group.Conclusion:Complication of respiratory virus infection can aggravate the airway remodeling and systemic inflammation in children with asthma.展开更多
Objective:To study the effect of inhalant combined with Dingchuan Zhike decoction therapy on the airway remodeling, inflammation and PARC/CCL-18 pathways in patients with cough variant asthma.Methods: A total of 60 pa...Objective:To study the effect of inhalant combined with Dingchuan Zhike decoction therapy on the airway remodeling, inflammation and PARC/CCL-18 pathways in patients with cough variant asthma.Methods: A total of 60 patients with cough variant asthma who were treated in our hospital between January 2014 and May 2016 were collected and divided into the control group (n=30) who received conventional inhalant treatment and the observation group (n=30) who received inhalant combined with Dingchuan Zhike decoction treatment according to single-blind randomized controlled method, and the treatment lasted for 6 months. Before treatment and after 6 months of treatment, high-resolution CT was used to determine the airway remodeling index levels, RIA method was used to detect the peripheral blood airway remodeling index contents, and enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of inflammatory mediators in induced sputum and the PARC/CCL-18 in serum.Results: Before treatment, the differences in the airway remodeling degree as well as the contents of inflammatory mediators and PARC/CCL-18 were not statistically significant between the two groups. After 6 months of treatment, CT airway remodeling indexes LA and TA levels of observation group were higher than those of control group while WA level was lower than that of control group, and peripheral blood airway remodeling indexes CTGF, YKL-39, MMP-9 and TIMP-1 contents were lower tha=n those of control group;inflammatory mediators IL-5, IL-6 and IL-8 contents in induced sputum of observation group were lower than those of control group, and serum PARC/CCL-18 content was lower than that of control group.Conclusion:Inhalant combined with Dingchuan Zhike decoction can inhibit the airway remodeling and reduce the airway inflammation in patients with cough variant asthma.展开更多
Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(...Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(IL-6/JAK2/STAT3) signal axis. Methods: We separated 42 healthy male SD rats into two groups, a control group (7) and a model group (35).The model group was sensitized with a combination of ovalbumin (OVA) and aluminum hydroxide for 2 weeks, while the control group was given an equal amount of physiological saline.After 2 weeks, the modeling group was randomly divided into Model group, Yanghe Pingchuan Granules high, medium and low dose groups and Dexamethasone group, each group consisted of 7 animals. After 4 weeks, OVA atomization and gavage were used for stimulation and treatment. Yanghe Pingchuan Granules high, middle and low groups were given 15.48, 7.74, 3.87 g∙kg-1 Yanghe Pingchuan Granules daily, dexamethasone group was given 0.0625 mg∙kg-1 dexamethasone daily, and the other groups were given the same amount of normal saline. HE, PAS and Masson staining were used to observe the lung histopathological changes in rats. The levels of interleukin-6, IL-23 and IL-17A were detected by ELISA. The expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 in lung tissues were detected by Western blot. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of IL-6, JAK2 and STAT3 in rat lung tissue. Results: The lung tissue structure of the model group was severely damaged compared to the control group, accompanied by a great many of inflammatory cell infiltration, goblet cell hyperplasia, subepithelial collagen fiber deposition and airway epithelial thickening were more obvious. The expressions of IL-6, IL- 23 and IL-17A in serum were significantly increased (P<0.01), the protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and the mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly increased (P<0.01);Compared with the model group, inflammatory cell infiltration, goblet cell proliferation, subepithelial collagen fiber deposition and airway epithelial thickening were significantly reduced in each administration group, and the expressions of IL-6, IL-23 and IL-17A in serum were significantly decreased (P< 0.01). The protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly decreased (P<0.01). Conclusion: Yanghe Pingchuan Granules can significantly alleviate airway remodeling in asthmatic rats, and its mechanism may be through inhibiting the IL-6/JAK2/STAT3 signal axis.展开更多
Asthma is a chronic lung disease that primarily affects the lower respiratory tract in more than 300 million people worldwide.Asthma is often triggered by exposure to certain substances or conditions,such as allergens...Asthma is a chronic lung disease that primarily affects the lower respiratory tract in more than 300 million people worldwide.Asthma is often triggered by exposure to certain substances or conditions,such as allergens or cold air.The overreaction to the allergens causes inflammation and narrowing of the airway,which leads to episodic or persistent symptoms including shortness of breath,nocturnal cough,chest tightness,and wheezing.展开更多
Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disor...Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disorders,notably including pulmonary arterial hypertension(PAH).However,the mechanism of action of MFJT on PAH remains unknown.Methods:In this study,a monocrotaline-induced PAH rat model was established and treated with MFJT.The therapeutic effects of MFJT on PAH rat model were evaluated.Network pharmacology was conducted to screen the possible targets for MFJT on PAH,and the molecular docking between the main active components and the core targets was carried out.The key targets identified from network pharmacology were tested.Results:Results showed significant therapeutic effects of MFJT on PAH rat model.Analysis of network pharmacology revealed several potential targets related to apoptosis,inflammation,oxidative stress,and vascular remodeling.Molecular docking showed that the key components were well docked with the core targets.Further experimental validation results that MFJT treatment induced apoptosis(downregulated Bcl-2 levels and upregulated Bax levels in lung tissue),inhibited inflammatory response and oxdative stress(decreased the levels of IL-1β,TNF-α,inducible NOS,and malondialdehyde,and increased the levels of endothelial nitric oxide synthase,nitric oxide,glutathione and superoxide dismutase),reduced the proliferation of pulmonary arterial smooth muscle cells(downregulated ET-1 andβ-catenin levels and ERK1/2 phosphorylation,increased GSK3βlevels).Conclusion:Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis,inhibition of inflammation and oxidative stress,and the prevention of vascular remodeling.展开更多
Objective:Lung adenocarcinoma exhibits diverse genetic and morphological backgrounds,in addition to considerable differences in clinical pathology and molecular biological characteristics.Among these,the phenomenon of...Objective:Lung adenocarcinoma exhibits diverse genetic and morphological backgrounds,in addition to considerable differences in clinical pathology and molecular biological characteristics.Among these,the phenomenon of spread through air space(STAS),a distinct mode of lung cancer infiltration,has rarely been reported.Therefore,this study aimed to explore the relationship between STAS tumor cells and the clinical and molecular characteristics of patients with lung adenocarcinoma,as well as their impact on prognosis.Methods:This study included 147 patients who were diagnosed with lung adenocarcinoma at the Inner Mongolia Autonomous Region Cancer Institute between January 2014 and December 2017.Surgical resection specimens were retrospectively analyzed.Using univariate and multivariate Cox analyses,we assessed the association between STAS and the clinicopathological features and molecular characteristics of patients with lung adenocarcinoma.Furthermore,we investigated the effects on patient prognosis.In addition,we developed a column–line plot prediction model and performed internal validation.Results:Patients with positive STAS had a significantly higher proportion of tumors with a diameter≥2 cm,with infiltration around the pleura,blood vessels,and nerves,and a pathological stage>IIB than in STAS-negative patients(P<0.05).Cox multivariate survival analysis revealed that clinical stage,STAS status,tumor size,and visceral pleural invasion were independent prognostic factors influencing the 5-year progression-free survival in patients with lung adenocarcinoma.The predictive values and P values from the Hosmer-Lemeshow test were 0.8 and 0.2,respectively,indicating no statistical difference.Receiver operating characteristic curve analysis demonstrated areas under the curve of 0.884 and 0.872 for the training and validation groups,respectively.The nomogram model exhibited the best fit with a value of 192.09.Conclusions:Clinical stage,pleural invasion,vascular invasion,peripheral nerve invasion,tumor size,and necrosis are independent prognostic factors for patients with STAS-positive lung adenocarcinoma.The nomogrambased on the clinical stage,pleural invasion,vascular invasion,peripheral nerve invasion,tumor size,and necrosis showed good accuracy,differentiation,and clinical practicality.展开更多
Objective: To explore the effect of evidence-based quality control circle (QCC) in improving the implementation rate of airway management measures in adult critically ill patients. Methods: Based on the Joanna Briggs ...Objective: To explore the effect of evidence-based quality control circle (QCC) in improving the implementation rate of airway management measures in adult critically ill patients. Methods: Based on the Joanna Briggs Institute (JBI) evidence-based health care model, the best evidence of airway management in adult critically ill patients was obtained and applied to the clinic. Results: The total implementation rate of airway management measures in adult critically ill patients increased from 23.62% before the implementation of quality control circle to 88.82%, and the pulmonary infection rate in critically ill patients decreased from 42.31% to 21.74%, with statistical significance between the two groups (P 0.05). Conclusion: Evidence-based quality control circle activities can standardize the practice standards of airway management in critically ill patients, reduce the occurrence of patients’ airway related complications, and improve clinical outcomes.展开更多
Objective To investigate the relationship between the expression of trannsient receptor potential vanilloid(TRPV1)and the severity of airway remodeling in elderly patients with chronic obstructive pulmonary disease(CO...Objective To investigate the relationship between the expression of trannsient receptor potential vanilloid(TRPV1)and the severity of airway remodeling in elderly patients with chronic obstructive pulmonary disease(COPD).Methods According to airflow obstruction severity,totally 100 cases of elderly patients with展开更多
OBJECTIVE Airway wall remodeling(AWR),which refers to structural changes in the airway,is a key characteristic of asthma.Airway smooth muscle(ASM)cell hypertrophy and hyperplasia contributes to AWR.Glucocorticoids,whi...OBJECTIVE Airway wall remodeling(AWR),which refers to structural changes in the airway,is a key characteristic of asthma.Airway smooth muscle(ASM)cell hypertrophy and hyperplasia contributes to AWR.Glucocorticoids,which are used as first line therapy for the treatment of asthma,reduce ASM proliferation but the magnitude of their anti-proliferative actions is dependent on the mitogen used.Moreover,glucocorticoid therapy is accompanied by many side effects.Artesunate,a semi-synthetic artemisinin derivative,has been widely used to treat malaria with minimal toxicity.Artesunate has been shown to attenuate allergic airway inflammation in mice.However,its role in treating AWR in asthma is not known.In this study,we hypothesize that artesunate has anti-proliferative actions on ASM cells,potentially reversing AWR.METHODS and RESULTS Quiescent primary human ASM cells were pre-treated(1h)with artesunate(3,10,30μmol·L-1)before being stimulated with either FBS(10%)or thrombin(0.3U·mL-1).Following 48 h stimulation with mitogen,cells were counted using a haemocytometer.Dexamethasone(Dex,100nmol·L-1)was used as a positive control.Artesunate concentration-dependently reduced cell number and the magnitude of inhibition appeared to be non-mitogen dependent.Moreover,we examined the effect of artesunate on two important signalling proteins involved in cell proliferation,ERK1/2phosphorylation and cyclin D1 protein levels.Artesunate reduced cyclin D1 protein levels significantly following 20 h stimulation with either thrombin or FBS but had no effect on ERK1/2 phosphorylation following 6h stimulation.Importantly,artesunate(30μmol·L-1),but not Dex,inhibited the phosphorylation of Akt,which is upstream of cyclin D1.Next,we show that the inhibitory effect of artesunate,but not Dex,on ASM cell number is retained at least 24h post-treatment following stimulation with FBS.In an acute murine model of allergic asthma,artesunate treatment decreased sm-α-actin positive cells and cyclin D1 protein abundance in the ovalbumin sensitized and challenged mice.CONCLUSION We have shown that artesunate regulates the PI3K/Akt pathway to inhibit the proliferation of primary human cultured ASM cells.This is an alternative mode of action,in comparison to glucocorticoids such as Dex.The anti-proliferative effect of artesunate was further validated in vivo.Thus,our study provides a basis for the future development of artesunate as a novel anti-AWR agent that targets ASM hyperplasia via the PI3K/Akt pathway.Moreover,artesunate may be used as an add-on therapy for asthmatic patients.展开更多
文摘According to modern research,the pathogenesis of asthma mainly includes airway inflammation,airway hyperresponsiveness,airway remodeling,etc.Airway remodeling is the key factor that leads to the progress of asthma,and it is also the main factor that leads to airway hyperresponsiveness and irreversible airflow restriction.Traditional Chinese medicine believes that"phlegm and blood stasis"block the airway and narrow the lumen is the most important factor in the treatment of asthma.
文摘Objective:Use data mining techniques to explore the rule of Chinese medicine used for airway remodeling.Methods:Search the literature on Chinese medicine use for airway remodeling in the past 20 years.With the help of WPS Office Excel 11.1,IBM SPSS Statistics 23.0 and SPSS Modeler 18.0 software,prescriptions were analyzed for the frequency of drug use,the four natures,the five flavours and the channel tropism,cluster analysis and association analysis of high-frequency drugs.Results:There were 58 Chinese medicine prescriptions for airway remodeling be found,involving 105 Chinese medicines,the most frequent channel tropism were spleen,stomach,lung,large intestine,liver and gallbladder,the most frequent use of the five flavors was sour,sweet and pungent,the highest frequency of the four natures was cold and hot,cluster analysis yielded eight drug aggregation groups,and association rule analysis yielded five groups of high-frequency drug pairs.Conclusion:The main TCM treatments for airway remodeling are expelling phlegm,relieving cough,asthma calming,expelling blood stasis and deficiency tonifying.The results of this study can provide ideas for compounding and drug selection for subsequent studies.
文摘In order to investigate the effect of nuclear factor κB (NF κB) on airway remodeling in asthmatic rats, 18 Wistar rats were divided into three groups: asthmatic group; pyrrolidine dithiocarbamate (PDTC) group, in which rats were injected intraperitoneally with NF κB specific inhibitor PDTC (100 mg/kg) before ovalbumin (OVA) challenge; control group. The NF κB activity and the expression of inhibitory protein κBα (I κBα) in airway were detected by electrophoretic mobility shift assay (EMSA), Western blot and immunohistochemistry respectively. The infiltration of inflammatory cells, the number of Goblet cells, the area of collagen and smooth muscle in airway were measured by means of image analysis system. The results showed that with the up regulation of airway NF κB activity in asthmatic group, the number of goblet cells (3.08±0.86/100 μm basement membrane (BM)), the area of collagen (24.71±4.24 μm 2/μm BM) and smooth muscle (13.81±2.11 μm 2/μm BM) in airway were significantly increased ( P <0.05) as compared with control group (0.14±0.05/100 μm BM, 14.31 ±3.16 μm 2/μm BM and 7.67±2.35 μm 2/μm BM respectively) and PDTC group (0.33±0.14/100 μm BM, 18.16±2.85 μm 2/μm BM and 8.95±2.16 μm 2/μm BM respectively). However, there was no significant difference between PDTC group and control group ( P >0.05). It was concluded that the activity of NF κB is increased in airway of asthmatic rats. Inhibition of NF κB activation can attenuate constructional changes in asthma airway, suggesting NF κB may contribute to asthmatic airway remodeling.
文摘Objective:To study the effect of adjuvant N-acetylcysteine (NAC) effervescent tablets therapy on cardiopulmonary function and airway remodeling in patients with stable chronic obstructive pulmonary disease (COPD).Methods: Patients with stable COPD treated in Zigong Third People's Hospital and West China Hospital, Sichuan University between May 2014 and October 2016 were selected and randomly divided into two groups, NAC group received N-acetylcysteine effervescent tablets combined with routine treatment, and control group received routine treatment. Before treatment as well as 2 weeks and 4 weeks after treatment, oxidative stress indexes and airway remodeling indexes in serum as well as inflammatory response indexes in peripheral blood were determined.Results: MDA, PC, 8-OHdG, MMP2, MMP3 and MMP9 contents in serum as well as NLRP3, ASC, p38MAPK and TREM-1 mRNA expression levels in peripheral blood mononuclear cells of both groups of patients after treatment were significantly lower than those before treatment while TAC levels as well as TIMP1 and TIMP2 contents in serum were significantly higher than those before treatment, and MDA, PC, 8-OHdG, MMP2, MMP3 and MMP9 contents in serum a well as NLRP3, ASC, p38MAPK and TREM-1 mRNA expression levels in peripheral blood mononuclear cells of NAC group after treatment were significantly lower than those of control group while TAC levels as well as TIMP1 and TIMP2 contents in serum were significantly higher than those of control group.Conclusion:Adjuvant NAC effervescent tablets treatment of stable COPD can improve the effect of oxidative stress and inflammatory response on cardiopulmonary function, and inhibit the airway remodeling caused by protease activation.
文摘Objective:To study the influence of budesonide and salbutamol atomization inhalation on Th17/Treg balance in patients with bronchial asthma and its correlation with airway remodeling.Methods:A total of 90 patients with bronchial asthma who received systemic treatment in our hospital between July 2013 and April 2016 were divided into control group (n=45) and observation group (n=45) according to random number table. Patients in the control group were treated with salbutamol atomization inhalation alone while those in observation group were treated with budesonide and salbutamol atomization inhalation. The Th17/Treg ratio in peripheral blood as well as serum contents of airway remodeling-related indicators was compared between two groups before and after treatment. The correlation between Th17/Treg balance and airway remodeling in patients with bronchial asthma was detected by Pearson test. Results:Before treatment, the differences in peripheral blood Th17/Treg ratio as well as serum contents of inflammatory mediators, growth factor indexes and collagen metabolism indexes were not statistically significant between two groups of patients. After treatment, peripheral blood Th17/Treg ratio in observation group was lower than that in control group, serum CRP, IL-8, IL-13 and TNF- contents in observation group were lower than those in control group, serum PDGF-BB, b-FGF and VEGF contents in observation group were lower than those in control group, and serum HA, PCⅢ and LN contents in observation group were lower than those in control group. The Th17/Treg ratio in patients with bronchial asthma after treatment was positively correlated with the levels of airway remodeling-related indexes.Conclusion:Budesonide combined with salbutamol atomization inhalation can optimize the Th17/Treg balance in patients with bronchial asthma, and Th17/Treg is directly correlated to the degree of airway remodeling.
文摘Objective: To observe the expression of proto-oncogenes in the process of airway remodeling in asthma. Methods: Guinea pig was used as an asthma model challenged by ovoglobulin. Dot-blot, Northern-blot molecular hybridization and immunohistochemistry techniques were used to detect the expression of c-fos, c-myc, c-jun and c-sis. Results: Expression of c-fos and c-myc mRNA could not be detected or detected at very low level in the control group. There were greatly increased expression of c-fos and c-myc mRNA after guinea pigs were challenged by ovoglobulin. Thirty minutes after the challenge, the expression of c-fos and c-myc mRNA reached to the peak and returned to normal level 4 h after the challenge. Immunohistochemistry studies showed that Fos, Myc, Jun and Sis expressed at low level in control group and increased after ovoglobulin stimulation. Immunohistochemically positive cells laid in the plasma of airway epithelium, in cell nucleus of bronchial epithelium and in the inflammatory cells.
文摘Objective: To explore the effect of Corbrin Capsule combined with routine western medicine on the airway remodeling process in patients with stable COPD. Methods: A total of 120 patients with stable COPD who were treated in the hospital between May 2014 and December 2016 were collected and divided into control group and observation group according to the random number table method, 60 cases in each group. The control group received routine western medicine treatment, and the observation group received Corbrin Capsule combined with routine western medicine treatment. The differences in serum levels of inflammatory factors, growth factors and fibrosis indexes were compared between the two groups before and after treatment. Results: Before treatment, difference in serum levels of inflammatory factors, growth factors and fibrosis indexes were not statistically significant between the two groups of patients. After 8 weeks of treatment, serum IL-2, IL-4, IL-8, IL-18, VEGF, b-FGF, NGF, LN, HA, PⅢNP and C-Ⅳ levels of both groups of patients were significantly lower than those before treatment, and serum IL-2, IL-4, IL-8, IL-18, VEGF, b-FGF, NGF, LN, HA, PⅢNP and C-Ⅳ levels of observation group were lower than those of control group. Conclusion: Corbrin Capsule combined with routine western medicine treatment can effectively inhibit the fibrosis process in patients with stable COPD.
文摘Objective: To study the effect of intermittent anaerobic exercise combined with inhalant therapy on airway remodeling and inflammatory response in children with asthma. Methods:A total of 92 children who were diagnosed with bronchial asthma in Zigong Third People's Hospital between June 2015 and February 2017 were selected as the research subjects and randomly divided into exercise group and control group who received intermittent anaerobic exercise combined with inhalant therapy and regular inhalant therapy respectively. Results:4 weeks and 8 weeks after intervention, serum MMP2, MMP3, MMP9, ADAM33,TGF-β1, Smad3, CTGF, PINP, PIIINP, IL-4, IL-9, IL-21, TNF-α and hs-CRP levels of both groups of patients were significantly lower than those before intervention while TIMP1 levels were significantly higher than those before intervention, and serum MMP2, MMP3, MMP9, ADAM33,TGF-β1, Smad3, CTGF, PINP, PIIINP, IL-4, IL-9, IL-21, TNF-α and hs-CRP levels of exercise group were significantly lower than those of control group while TIMP1 levels were significantly higher than those of control group. Conclusion: Intermittent anaerobic exercise combined with inhalant therapy can improve airway remodeling and inflammatory response in children with asthma.
文摘Objective:To study the effect of pediatric asthma complicated by respiratory virus infection on airway remodeling and inflammation.Methods:A total of 41 children with asthma complicated by respiratory virus infection who were treated in our hospital between May 2012 and March 2016 were collected as observation group, and 50 children with asthma alone who were treated in our hospital during the same period were selected as control group. High-resolution CT was used to determine the right upper lobe apical segment (RB1) and the left lower lobe posterior basal segment (LB10) airway remodeling parameters of two groups of patients, and serum airway remodeling index and inflammatory factor contents were detected. Results: LA, WA and TA levels of RB1 and LB10 of observation group were significantly lower than those of control group, serum airway remodeling indexes TGF-β1, Smad3, PⅠNP and PⅢNP contents were higher than those of control group, serum inflammation indexes IL-4, IL-5 and TNF-α contents were higher than those of control group.Conclusion:Complication of respiratory virus infection can aggravate the airway remodeling and systemic inflammation in children with asthma.
文摘Objective:To study the effect of inhalant combined with Dingchuan Zhike decoction therapy on the airway remodeling, inflammation and PARC/CCL-18 pathways in patients with cough variant asthma.Methods: A total of 60 patients with cough variant asthma who were treated in our hospital between January 2014 and May 2016 were collected and divided into the control group (n=30) who received conventional inhalant treatment and the observation group (n=30) who received inhalant combined with Dingchuan Zhike decoction treatment according to single-blind randomized controlled method, and the treatment lasted for 6 months. Before treatment and after 6 months of treatment, high-resolution CT was used to determine the airway remodeling index levels, RIA method was used to detect the peripheral blood airway remodeling index contents, and enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of inflammatory mediators in induced sputum and the PARC/CCL-18 in serum.Results: Before treatment, the differences in the airway remodeling degree as well as the contents of inflammatory mediators and PARC/CCL-18 were not statistically significant between the two groups. After 6 months of treatment, CT airway remodeling indexes LA and TA levels of observation group were higher than those of control group while WA level was lower than that of control group, and peripheral blood airway remodeling indexes CTGF, YKL-39, MMP-9 and TIMP-1 contents were lower tha=n those of control group;inflammatory mediators IL-5, IL-6 and IL-8 contents in induced sputum of observation group were lower than those of control group, and serum PARC/CCL-18 content was lower than that of control group.Conclusion:Inhalant combined with Dingchuan Zhike decoction can inhibit the airway remodeling and reduce the airway inflammation in patients with cough variant asthma.
基金The Sixth Batch of Special Support Plans in Anhui Province(No.dlPtzjh20200050)Key Natural Science Research Project of Higher Education Institutions in Anhui Province(No.KJ2020A0426)。
文摘Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(IL-6/JAK2/STAT3) signal axis. Methods: We separated 42 healthy male SD rats into two groups, a control group (7) and a model group (35).The model group was sensitized with a combination of ovalbumin (OVA) and aluminum hydroxide for 2 weeks, while the control group was given an equal amount of physiological saline.After 2 weeks, the modeling group was randomly divided into Model group, Yanghe Pingchuan Granules high, medium and low dose groups and Dexamethasone group, each group consisted of 7 animals. After 4 weeks, OVA atomization and gavage were used for stimulation and treatment. Yanghe Pingchuan Granules high, middle and low groups were given 15.48, 7.74, 3.87 g∙kg-1 Yanghe Pingchuan Granules daily, dexamethasone group was given 0.0625 mg∙kg-1 dexamethasone daily, and the other groups were given the same amount of normal saline. HE, PAS and Masson staining were used to observe the lung histopathological changes in rats. The levels of interleukin-6, IL-23 and IL-17A were detected by ELISA. The expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 in lung tissues were detected by Western blot. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of IL-6, JAK2 and STAT3 in rat lung tissue. Results: The lung tissue structure of the model group was severely damaged compared to the control group, accompanied by a great many of inflammatory cell infiltration, goblet cell hyperplasia, subepithelial collagen fiber deposition and airway epithelial thickening were more obvious. The expressions of IL-6, IL- 23 and IL-17A in serum were significantly increased (P<0.01), the protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and the mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly increased (P<0.01);Compared with the model group, inflammatory cell infiltration, goblet cell proliferation, subepithelial collagen fiber deposition and airway epithelial thickening were significantly reduced in each administration group, and the expressions of IL-6, IL-23 and IL-17A in serum were significantly decreased (P< 0.01). The protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly decreased (P<0.01). Conclusion: Yanghe Pingchuan Granules can significantly alleviate airway remodeling in asthmatic rats, and its mechanism may be through inhibiting the IL-6/JAK2/STAT3 signal axis.
文摘Asthma is a chronic lung disease that primarily affects the lower respiratory tract in more than 300 million people worldwide.Asthma is often triggered by exposure to certain substances or conditions,such as allergens or cold air.The overreaction to the allergens causes inflammation and narrowing of the airway,which leads to episodic or persistent symptoms including shortness of breath,nocturnal cough,chest tightness,and wheezing.
基金supported by the Qingdao Medical Research Guidance Plan(2020-WJZD049).
文摘Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disorders,notably including pulmonary arterial hypertension(PAH).However,the mechanism of action of MFJT on PAH remains unknown.Methods:In this study,a monocrotaline-induced PAH rat model was established and treated with MFJT.The therapeutic effects of MFJT on PAH rat model were evaluated.Network pharmacology was conducted to screen the possible targets for MFJT on PAH,and the molecular docking between the main active components and the core targets was carried out.The key targets identified from network pharmacology were tested.Results:Results showed significant therapeutic effects of MFJT on PAH rat model.Analysis of network pharmacology revealed several potential targets related to apoptosis,inflammation,oxidative stress,and vascular remodeling.Molecular docking showed that the key components were well docked with the core targets.Further experimental validation results that MFJT treatment induced apoptosis(downregulated Bcl-2 levels and upregulated Bax levels in lung tissue),inhibited inflammatory response and oxdative stress(decreased the levels of IL-1β,TNF-α,inducible NOS,and malondialdehyde,and increased the levels of endothelial nitric oxide synthase,nitric oxide,glutathione and superoxide dismutase),reduced the proliferation of pulmonary arterial smooth muscle cells(downregulated ET-1 andβ-catenin levels and ERK1/2 phosphorylation,increased GSK3βlevels).Conclusion:Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis,inhibition of inflammation and oxidative stress,and the prevention of vascular remodeling.
基金Funded by the Health Science and Technology Program of Inner Mongolia Autonomous Region(no.202201061)Supported by the Joint Project of theMillion Science and Technology Initiatives of Inner Mongolia Medical University(no.YKD2020KJBW(LH)057).
文摘Objective:Lung adenocarcinoma exhibits diverse genetic and morphological backgrounds,in addition to considerable differences in clinical pathology and molecular biological characteristics.Among these,the phenomenon of spread through air space(STAS),a distinct mode of lung cancer infiltration,has rarely been reported.Therefore,this study aimed to explore the relationship between STAS tumor cells and the clinical and molecular characteristics of patients with lung adenocarcinoma,as well as their impact on prognosis.Methods:This study included 147 patients who were diagnosed with lung adenocarcinoma at the Inner Mongolia Autonomous Region Cancer Institute between January 2014 and December 2017.Surgical resection specimens were retrospectively analyzed.Using univariate and multivariate Cox analyses,we assessed the association between STAS and the clinicopathological features and molecular characteristics of patients with lung adenocarcinoma.Furthermore,we investigated the effects on patient prognosis.In addition,we developed a column–line plot prediction model and performed internal validation.Results:Patients with positive STAS had a significantly higher proportion of tumors with a diameter≥2 cm,with infiltration around the pleura,blood vessels,and nerves,and a pathological stage>IIB than in STAS-negative patients(P<0.05).Cox multivariate survival analysis revealed that clinical stage,STAS status,tumor size,and visceral pleural invasion were independent prognostic factors influencing the 5-year progression-free survival in patients with lung adenocarcinoma.The predictive values and P values from the Hosmer-Lemeshow test were 0.8 and 0.2,respectively,indicating no statistical difference.Receiver operating characteristic curve analysis demonstrated areas under the curve of 0.884 and 0.872 for the training and validation groups,respectively.The nomogram model exhibited the best fit with a value of 192.09.Conclusions:Clinical stage,pleural invasion,vascular invasion,peripheral nerve invasion,tumor size,and necrosis are independent prognostic factors for patients with STAS-positive lung adenocarcinoma.The nomogrambased on the clinical stage,pleural invasion,vascular invasion,peripheral nerve invasion,tumor size,and necrosis showed good accuracy,differentiation,and clinical practicality.
文摘Objective: To explore the effect of evidence-based quality control circle (QCC) in improving the implementation rate of airway management measures in adult critically ill patients. Methods: Based on the Joanna Briggs Institute (JBI) evidence-based health care model, the best evidence of airway management in adult critically ill patients was obtained and applied to the clinic. Results: The total implementation rate of airway management measures in adult critically ill patients increased from 23.62% before the implementation of quality control circle to 88.82%, and the pulmonary infection rate in critically ill patients decreased from 42.31% to 21.74%, with statistical significance between the two groups (P 0.05). Conclusion: Evidence-based quality control circle activities can standardize the practice standards of airway management in critically ill patients, reduce the occurrence of patients’ airway related complications, and improve clinical outcomes.
文摘Objective To investigate the relationship between the expression of trannsient receptor potential vanilloid(TRPV1)and the severity of airway remodeling in elderly patients with chronic obstructive pulmonary disease(COPD).Methods According to airflow obstruction severity,totally 100 cases of elderly patients with
基金This study was supported by the Scientific Research and Technological Development Program Project of Guangxi Province （10124001A-32）, the Young Science Foundation of Guangxi Medical University （GXMUSF201206） and the Innovation Project of Guangxi Graduate Education （YCBZ2013014）.
文摘OBJECTIVE Airway wall remodeling(AWR),which refers to structural changes in the airway,is a key characteristic of asthma.Airway smooth muscle(ASM)cell hypertrophy and hyperplasia contributes to AWR.Glucocorticoids,which are used as first line therapy for the treatment of asthma,reduce ASM proliferation but the magnitude of their anti-proliferative actions is dependent on the mitogen used.Moreover,glucocorticoid therapy is accompanied by many side effects.Artesunate,a semi-synthetic artemisinin derivative,has been widely used to treat malaria with minimal toxicity.Artesunate has been shown to attenuate allergic airway inflammation in mice.However,its role in treating AWR in asthma is not known.In this study,we hypothesize that artesunate has anti-proliferative actions on ASM cells,potentially reversing AWR.METHODS and RESULTS Quiescent primary human ASM cells were pre-treated(1h)with artesunate(3,10,30μmol·L-1)before being stimulated with either FBS(10%)or thrombin(0.3U·mL-1).Following 48 h stimulation with mitogen,cells were counted using a haemocytometer.Dexamethasone(Dex,100nmol·L-1)was used as a positive control.Artesunate concentration-dependently reduced cell number and the magnitude of inhibition appeared to be non-mitogen dependent.Moreover,we examined the effect of artesunate on two important signalling proteins involved in cell proliferation,ERK1/2phosphorylation and cyclin D1 protein levels.Artesunate reduced cyclin D1 protein levels significantly following 20 h stimulation with either thrombin or FBS but had no effect on ERK1/2 phosphorylation following 6h stimulation.Importantly,artesunate(30μmol·L-1),but not Dex,inhibited the phosphorylation of Akt,which is upstream of cyclin D1.Next,we show that the inhibitory effect of artesunate,but not Dex,on ASM cell number is retained at least 24h post-treatment following stimulation with FBS.In an acute murine model of allergic asthma,artesunate treatment decreased sm-α-actin positive cells and cyclin D1 protein abundance in the ovalbumin sensitized and challenged mice.CONCLUSION We have shown that artesunate regulates the PI3K/Akt pathway to inhibit the proliferation of primary human cultured ASM cells.This is an alternative mode of action,in comparison to glucocorticoids such as Dex.The anti-proliferative effect of artesunate was further validated in vivo.Thus,our study provides a basis for the future development of artesunate as a novel anti-AWR agent that targets ASM hyperplasia via the PI3K/Akt pathway.Moreover,artesunate may be used as an add-on therapy for asthmatic patients.
