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Background: Traditional Chinese medicine (TCM) is effective for the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD); however, there is no objective index for the evaluation of TCM syndrome efficacy. This study aimed to screen biomarkers related to the efficacy of TCM syndrome using metabolomics. Methods: We recruited AECOPD patients with phlegm-heat congesting lung (PH)/phlegm-damp amassing lung (PD) syndrome and treated them with Chinese herbal medicine (Qingre Huatan or Zaoshi Huatan granules) in addition to conventional medicine for 7 days. Data on clinical symptoms and sign scores, modified British Medical Research Council (mMRC), COPD assessment test (CAT), and inflammation indicators, including white blood cell (WBC) count, percentage of neutrophil count (NEU%), and C-reactive protein (CRP), were collected before and after treatment to evaluate the therapeutic effect. Serum samples were collected before and after treatment for metabolomic analysis to screen differential metabolites. Results: A total of 69 patients with AECOPD were enrolled, including 41 and 28 patients in the PH and PD groups, respectively. The clinical symptoms and sign scores, CAT, mMRC, NEU%, and CRP levels after treatment were lower than those before treatment in both groups (p < 0.05). Serum metabolomics analysis showed that there were 13 differential metabolites in the PH group and 16 differential metabolites in the PD group before and after treatment (p < 0.05, variable importance projection (VIP) ≥ 1.00). In the PH group, lysophosphatidylcholine (LPC) (16:0), LPC (17:1), LPC (18:3), LPC (18:2), and LPC (17:0) negatively correlated with clinical symptoms and sign scores (p < 0.05); LPC (16:0), LPC (17:1), LPC (16:1), and LPC (17:0) negatively correlated with WBC (p < 0.05) and NEU% (p < 0.05); and LPC (16:0) negatively correlated with CRP levels. In the PD group, L-phenylalanine positively correlated with CRP levels (p < 0.05), and 2-methylbutyroylcarnitine positively correlated with clinical symptoms and sign (p < 0.05) and CAT scores (p < 0.05). DL-carnitine positively correlated with clinical symptoms and sign scores (p < 0.05). Conclusion: Serum metabolites may be potential indicators to objectively evaluate the efficacy of TCM syndromes; however, further large controlled trials are required to verify these findings.
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Chronic obstructive pulmonary disease(COPD)poses a serious threat to human health and carries a heavy burden of disease.The disease burden mainly includes traditional epidemiological indicators such as morbidity,disability rate,and mortality rate,as well as economic burden evaluation indicators such as direct economic burden,indirect economic burden,and intangible economic burden,as well as social/health burden evaluation indicators such as potential years of life reduction,disability adjusted life years,and quality adjusted life years.It summarized the existing methods for evaluating the burden of COPD diseases and proposed the following suggestions:(1)enriching economic burden research methods to comprehensively and accurately evaluate direct economic burden;(2)expanding the scope of economic burden research and improve the economic burden research of COPD;(3)strengthening information management and enhance the accuracy of disease burden data;(4)exploring multidimensional indicators and establish a COPD disease burden evaluation system;(5)strengthening relevant research and highlight the health economics advantages of traditional Chinese medicine intervention in COPD.It can provide references for establishing a COPD disease burden evaluation system and policy formulation.
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Objective:To observe the effect of lipopolysaccharide (LPS) induced conditioned medium of alveolar epithelial cells on the inflammatory response and cell damage of vascular endothelial cells, and explore its mechanism.Methods:The LPS induced type Ⅱ alveolar epithelial cells (A549) conditioned medium was used as a stimulus to induce human umbilical vein endothelial cells (HUVEC) damage. The cell counting kit-8 (CCK-8) was used to detect the effect of 0% (blank group), 12.5%, 25%, 50%, 75% and 100% A549 cell conditioned medium cultured for 6, 12, 24 and 48 hours on the cell viability of HUVEC. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)] and vasoactive substances [vascular endothelial growth factor (VEGF), endothelin-1 (ET-1)] in the supernatant. Phalloidin staining was used to observe the effects of A549 cells conditioned medium on cell morphology. The expressions of protein kinase B/nuclear factor-κB (AKT/NF-κB) pathway in HUVEC induced by conditioned medium was detected by Western blotting.Results:Compared with the blank group, A549 cells conditioned medium with concentrations of 12.5%, 25%, and 50% had no significant effects on cell viability of HUVEC after 6, 12, and 24 hours, but the activity of HUVEC decreased significantly after 48 hours. Therefore, 12.5%, 25%, 50% A549 cell conditioned medium stimulated for 24 hours was selected as the induction condition for follow-up experiments. Compared with the blank group, the level of IL-6 was significantly increased in 12.5% and 50% conditioned medium groups (ng/L: 2?438.95±64.89, 3?036.41±96.69 vs. 1?736.75±20.99, both P < 0.05), the level of TNF-α was significantly increased in 12.5% and 25% conditioned medium groups (ng/L: 174.08±11.09, 81.37±8.17 vs. 50.03±0.26, both P < 0.01), the levels of VEGF and ET-1 were significantly increased in 12.5%, 25% and 50% conditioned medium groups [VEGF (ng/L): 173.60±41.44, 192.49±12.38, 318.89±27.90 vs. 66.68±19.65; ET-1 (ng/L): 54.88±1.37, 36.69±0.29, 24.07±0.73 vs. 10.67±0.25, all P < 0.01]. Phalloidin staining showed that HUVEC induced by 25% A549 cells conditioned medium were irregular in shape, uneven in size, disordered in arrangement, widened in gap, dense and unclear in microfilament structure and serrated in cell membrane. Furthermore, the average fluorescence intensity of 25% conditioned medium group significantly increased compared to the blank group (67?205.60±3?430.40 vs. 56?272.67±7?650.95, P < 0.05). Western blotting showed that compared with the blank group, the expression of HUVEC cells phosphonated inhibitor α of NF-κB (p-IκBα) was significantly decreased in the 12.5%, 25%, and 50% conditioned medium groups (p-IκBα/IκBα: 0.38±0.08, 0.67±0.12, 0.31±0.07 vs. 1.00±0.00, all P < 0.01), the expressions of phosphonated-AKT (p-AKT) and VEGF were significantly increased (p-AKT/AKT: 1.50±0.18, 1.42±0.27, 1.61±0.14 vs. 1.00±0.00, VEGF/GAPDH: 1.37±0.10, 1.53±0.22, 1.40±0.12 vs. 1.00±0.00, all P < 0.05), the expression of phosphonated NF-κB p65 (p-P65) was significantly increased in the 25% conditioned medium group (p-P65/P65: 1.45±0.14 vs. 1.00±0.00, P < 0.05). Conclusion:LPS induced conditional culture medium of alveolar epithelial cells induced endothelial cell damage via activating AKT/NF-κB pathway.
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N6-methyladenosine (m6A) is one of the most common post-transcriptional modifications of eukaryotic mRNA. The m6A modification accelerates mRNA metabolism and translation, and plays an important role in cell differentiation, embryonic development and stress response. As a reversible epigenetic modification, m6A modification plays an important role in many physiological and pathological processes. The m6A modification is closely related to the occurrence and progression of respiratory diseases, and the m6A modification regulatory factor may be a potential target for regulating respiratory diseases. This article reviews the role of m6A modification in the development of respiratory diseases such as lung cancer, acute lung injury (ALI), asthma, pulmonary fibrosis, and chronic obstructive pulmonary disease (COPD). The purpose of m6A modification is to provide a reference for the pathogenesis of respiratory diseases and the study of targets.
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ObjectiveTo analyze the development status and quality of clinical practice guidelines for the treatment of dominant diseases with Chinese patent medicines （CPMs）. MethodsDatabases were searched from Jan. 2019 to Dec.2023 to collect the published clinical practice guidelines of CPMs for the treatment of dominant diseases. The information about the title， the participants， clinical problems， outcomes， evidence grade， recommendations， and recommendation strength in the included clinical practice guidelines were collected， for which the development status was analyzed， and the quality was evaluated with the Scientific， Transparent and Applicable Rankings （STAR） tool for clinical practice guidelines. ResultsTotally， 34 guidelines were included， involving 273 kinds of CPMs. One to ten （with the medium five） clinical problems were proposed from 29 clinical practice guidelines respectively. All the guidelines divided the evidence into four grades according to Grade of Recommendation Assessment， Deve-lopement an Evaluation. And 28 guidelines had five levels of recommendation strength. A total of 344 recommendations were extracted， including 86 strong-recommendations， 191 weak-recommendations （including 36 weak recommendations only based on expert consensus） and 67 recommendations with unclear recommendation strength. All guidelines had high scores in the three areas of “clinical questions （94.20%）”， “evidence （91.45%）” and “recommendations （89.06%）”， while the scores in the three areas of “registry （22.06%）”， “protocol （19.00%）” and “accessibility （31.51%）” were low. The STAR recommended stars of 8 guidelines were 5.0~4.0 stars， while that of 18 guidelines were 3.5~2.5 stars， and 8 guidelines were 2.0~1.0 stars. The three guidelines with the highest recommended stars were depressive disorder， community-acquired pneumonia， and influenza in adult. ConclusionThere is a certain gap in the quality of the published clinical practice guidelines of CPMs， and the quality of the guidelines could be further improved in registry， protocols， funds， and accessibility.
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Idiopathic pulmonary fibrosis (IPF) is a common chronic interstitial fibrotic disease. During the fibrosis process, myofibroblasts are abnormally activated, collagen is deposited in large quantities and the biomechanical characteristics of lung tissue are significantly altered. In this paper, a systematic review about the changes in lung tissues, cellular biomechanical properties and biomechanical signals during the process of IPF was presented, and the in vitro reproduction of biomechanical features and therapeutic strategies for targeting biomechanics wassummarized, so as to provide references for clinical prevention and treatment of IPF.
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Objective:To systematically evaluate the distribution characteristics of traditional Chinese medicine (TCM) syndromes in adult influenza patients and to provide a basis for the TCM syndrome differentiation of influenza.Methods:The CNKI, CBM, Wanfang, VIP, PubMed, Embase, Cochrane Library databases were searched to collect cross -sectional studies on the distribution pattern of TCM syndromes in adult patients with influenza. The risk of bias assessment tool for cross -sectional studies developed by the Joanna Briggs Institute (JBI) evidence -based health care center was used to evaluate the literature quality, and the Stata 15.1 software was used to conduct a Meta -analysis of the pooled effect sizes of the included studies. Results:A total of 11 studies with 4 367 influenza patients were included. Quality assessment results of JBI showed that the risk bias was higher in the sample size calculation, and the description of sampling modalities and response rate was unclear. There were 17 influenza syndromes after specification, and a single group rate Meta -analysis was performed of the syndromes with ≥ 50 incident cases showed that there were 9 syndromes with an incidence ≥ 10% and statistical significance, the top 5 syndromes were syndrome of wind and heat invading the defense [ n = 1 583, RATE = 34.3%, 95% confidence interval (95% CI) was 22.2%-46.3%], syndrome of exterior cold and interior heat ( n = 1 122, RATE = 36.1%, 95% CI was 21.2%-51.1%), syndrome of wind -cold fettering the exterior ( n = 860, RATE = 19.4%, 95% CI was 10.7%-28.0%), syndrome of heat and toxin in the lung ( n = 217, RATE = 17.1%, 95% CI was 9.1%-25.0%), and syndrome of disease involving both defense phase and qi phase ( n = 184, RATE = 38.8%, 95% CI was 14.2%-63.5%). The results of the subgroup analysis in different geographical regions showed that the frequency of distribution of syndrome of wind and heat invading the defense and heat and toxin in the lung was higher in the South (RATE: 36.5%, 18.6%) than in the North (RATE: 30.9%, 15.4%), and the frequency of distribution of syndrome of wind -cold fettering the exterior and exterior cold and interior heat in the North (RATE: 23.8%, 40.1%) was higher than that in the South (RATE: 15.7%, 32.3%). Conclusions:There are 9 common TCM syndromes of influenza, including wind and heat invading the defense syndrome, exterior cold and interior heat syndrome, wind -cold fettering the exterior syndrome, heat and toxin in the lung syndrome, disease involving both defense phase and qi phase syndrome, wind and heat complicated by dampnessinvading the surface syndrome, wind and cold complicated by dampnessinvading the surface syndrome, defense phase syndrome and dampness and heatinvading the surface syndrome, which can provide a reference for the TCM syndrome differentiation and treatment of influenza.
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After systematically reviewing the syndrome distribution， evolution， diagnostic criteria， effectiveness evaluation and genomics study on acute exacerbation of chronic obstructive pulmonary disease （AECOPD） in the past decade， we found that there are problems such as inconsistency in the nomenclature of syndrome， lack of quantitative diagnostic tools for syndrome， less developed evaluation tools for syndrome efficacy， and singularity of genomics technique. Based on this， it was proposed that we should pay attention to the standardisation of syndrome naming， strengthen the research on quantitative diagnostic methods， establish standardised and quantitative diagnostic tools， further improve the existing assessment tools of syndrome effectiveness， and integrate the existing genomics techniques to conduct research， so as to support the further research on AECOPD syndromes.
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Objective To explore the distribution of common syndromes in sepsis based on literature data mining.Methods The literature related to sepsis symptoms analysis included in China National Knowledge Infrastructure(CNKI),Chinese Biomedical Literature Database(CBM),VIP database(VIP)and Wanfang Data were searched by computer to extract relevant information and establish a database.Analysis of common syndromes and symptoms of sepsis by frequency statistics.Based on LTM-EAST algorithm of two-step hidden tree analysis,a symptom hidden structure model with frequency≥10 was constructed by Latern 5.0 software,and potential syndromes were inferred through comprehensive clustering.Symptoms with frequency＞5%were selected for factor analysis,common factors were extracted for further systematic cluster analysis,and potential syndromes were inferred according to the results.Based on the above results,the common syndromes and clinical characteristics of sepsis were analyzed.Results A total of 792 literatures and 961 syndromes records and 877 symptoms records were included,involving 48 syndromes after the regulation,with high frequency of pattern of blood stasis,pattern of yangming fu-organ excess,pattern of internal block of the heart orifices due to phlegm and heat,pattern of yang prostration,etc.The frequencies were 12.70%(122/961),9.68%(93/961),9.47%(91/961)and 7.80%(75/961).It involved 179 symptoms after the regulation,including high fever,red tongue,thirst,dysphoria,etc.The frequencies were 27.82%(244/877),27.36%(240/877),27.25%(239/877),25.54%(244/877).Forty-three hidden variables were obtained through implicit structure analysis,according to professional knowledge,12 potential syndromes were obtained by comprehensive clustering,including pattern of blood stasis,pattern of yangming fu-organ excess,pattern of phlegm and heat congesting in the lung,pattern of fire toxin entering the nutrient phase,pattern of Yin deficiency with exuberant heat,pattern of Yang prostration,pattern of Qi deficiency,pattern of Yang deficiency,pattern of turbid phlegm obstructing the lung,pattern of damp-heat encumbering the spleen,pattern of intense exuberant heat toxin,pattern of pathogenic factors repressing defensive Qi of lung.Twenty-five common factors were obtained by factor analysis,and 12 potential syndromes were inferred by systematic clustering,including pattern of heart-Yang deficiency,pattern of phlegm and heat congesting in the lung,pattern of yangming fu-organ excess,pattern of Yang prostration,pattern of intense exuberant heat toxin,pattern of Yang deficiency in spleen and kidney,pattern of Qi deficiency,pattern of phlegm and heat damaging Yin,pattern of Qi deficiency with blood stasis,pattern of Qi and Yin deficiency,pattern of pathogenic factors repressing defensive Qi of lung,and pattern of heat sinking into the pericardium.According to the standard of common traditional Chinese medicine(TCM)syndromes and their symptom characteristics,9 common syndromes of sepsis were finally obtained,including pattern of intense exuberant heat toxin,blood stasis,pattern of yangming fu-organ excess,pattern of phlegm and heat congesting in the lung,pattern of fire toxin entering,pattern of pathogenic factors repressing defensive Qi of lung,pattern of Qi and Yin deficiency,pattern of Qi deficiency,pattern of Yang prostration.Conclusion The symptoms and characteristics of common syndromes of sepsis are significant,which can provide evidence for the syndrome diagnosis standard of sepsis.
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Objective To explore the distribution of traditional Chinese medicine basic syndromes in sepsis,and to provide evidence for the establishment of diagnostic criteria of sepsis syndromes.Methods Literatures related to sepsis syndrome included in China National Knowledge Infrastructure(CNKI),Wanfang Data,VIP database(VIP)and Chinese Biomedical Literature Database(CBM)databases were searched from the establishment of the database to May 30,2020.Screen the literature and extract data,establish a database for statistical description and analysis of syndrome elements,basic syndromes and symptoms.Analyze the association rule of syndrome elements based on the Apriori algorithm.Based on the two-step hidden tree analysis LTM-EAST algorithm,a symptom latent structure model was constructed,and a comprehensive cluster analysis and model interpretation were performed.Results A total of 383 articles related to sepsis syndromes were included,involving 31 basic syndromes,146 symptoms and 29 syndromes elements.The basic syndromes with frequencies≥5%and cumulative composition ratios≥75%were heat and toxin syndrome,blood stasis syndrome,Yin deficiency syndrome,heat and closing syndrome,Qi deficiency syndrome,phlegm and heat syndrome,Yang prostration syndrome,Fu-organ excess syndrome,and Yang deficiency syndrome.Perform the association rule analysis on syndrome elements with a frequency＞5,obtaining 8 strong association rules,and inferring 7 basic syndromes,including Fu-organ excess syndrome,heat and toxin syndrome,heat and closing syndrome,phlegm clouding the heart syndrome,heat disturbing the heart spirit syndrome,phlegm and heat syndrome,phlegm block syndrome.The symptoms with frequency＞5 were analyzed by hidden structure,41 hidden variables and 82 hidden categories were obtained,and 11 comprehensive clustering models were obtained through comprehensive clustering.Eleven basic syndromes were inferred,including heat and toxin syndrome,blood stasis syndrome,Yin deficiency syndrome,heat and closing syndrome,Qi deficiency syndrome,phlegm and heat syndrome,Yang prostration syndrome,Fu-organ excess syndrome,Yang deficiency syndrome,Yingfen syndrome,and phlegm-dampness syndrome.Combined with all of methods above,9 basic syndromes,heat and toxin syndrome,blood stasis syndrome,Yin deficiency syndrome,heat and closing syndrome,Qi deficiency syndrome,phlegm and heat syndrome,Yang prostration syndrome,Fu-organ excess syndrome,and Yang deficiency syndrome were finally confirmed.Conclusion There are 9 common basic syndromes of sepsis,and the sufficient syndromes are mainly heat and toxin syndrome,blood stasis syndrome,heat and closing syndrome,phlegm and heat syndrome and Fu-organ excess syndrome,while the deficiency syndromes are mainly Yin deficiency syndrome,Qi deficiency syndrome,Yang prostration syndrome,and Yang deficiency syndrome,with each basic syndrome having certain symptom characteristics.
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Objective To exploring the mechanism of Jinshui Chenfei formula(JCF)in ameliorating silica(SiO2)-induced silicosis fibrosis based on endogenous metabolite changes.Methods A total of 32 SPF male Sprague-Dawley(SD)rats were divided into normal control group,model group,JCF group(9.72 g·kg-1·d-1),and Tetrandrine group(27 mg·kg-1·d-1)according to random number table method.The experimental silicosis model was established by intratracheal injection with SiO2 suspension(250 mg/kg)on day 1.From week 5-8,silicosis rats were treated with tetrandrine or JCF.On the end of week 8,the changes of pulmonary function index,including forced vital capacity(FVC),tidal volume(TV)and lung dynamic compliance(Cydn)were detected.The pathological changes of lung tissue were analyzed by hematoxyline-osin(HE)staining and Masson staining,the severity of focal alveolitis and fibrosis was also evaluated using the Szapiel scale and the Ashcroft scale,the positive staining of collagen Ⅰ(COL Ⅰ)and COL Ⅲ was detected using immunohistochemistry;the protein expression of transforming growth factor-β1(TGF-β1),fibronectin(FN),andα-smooth muscle actin(α-SMA)were measured by Western blotting.The rat serum samples were further screened for differential metabolites using ultra performance liquid chromatographytandem quadrupole time of flight mass spectrometr(UPLC-Q-TOF-MS)and pathway analysis was performed based on MetaboAnalyst 5.0.Results Compared with those in the normal control group,pathological changes such as alveolar structure destruction,the fibrous nodules encapsulated SiO2 particles were increased in lung tissues of rats in model group,alveolitis score and pulmonary fibrosis score were significantly higher(alveolitis score:2.62±0.27 vs.0.20±0.15,pulmonary fibrosis score:5.42±0.66 vs.0.50±0.84,both P<0.01);pulmonary function index including Cydn,FVC,and TV were significantly decreased[Cdyn(mL/cmH2O):0.26±0.03 vs.0.33±0.03,FVC(mL):8.09±0.47 vs.10.99±0.38,TV(mL):1.95±0.19 vs.2.53±0.26,all P<0.01];positive staining of COL Ⅰ,COL Ⅲ and ɑ-SMA,FN,TGF-β1 proteins expression showed higher in lung tissues[positive staining of COL Ⅰ(A value):13.47±1.76 vs.5.77±0.45;positive staining of COL Ⅲ(A value):10.39±0.47 vs.6.19±0.77,FN protein expression(FN/GAPDH):0.33±0.02 vs.0.21±0.07,α-SMA protein expression(α-SMA/GAPDH):1.78±0.16 vs.1.11±0.24,TGF-β1 protein expression(TGF-β1/GAPDH):0.52±0.10 vs.0.11±0.46,all P<0.01].Compared with the model group,the pathological changes of lung tissues were almost restored,alveolitis score and lung fibrosis score were significantly reduced in JCF and Tetrandrine groups(alveolitis score:1.10±0.15,1.33±0.31 vs.2.62±0.27,pulmonary fibrosis score:3.50±0.45,4.33±0.98 vs.5.42±0.66,all P<0.01);the pulmonary function index Cydn,FVC and TV were significantly increased[Cdyn(mL/cmH2O):0.32±0.05,0.31±0.04 vs.0.26±0.03,FVC(mL):9.41±0.85,8.70±0.92 vs.8.09±0.47,TV(mL):2.70±0.19,2.27±0.15 vs.1.95±0.19,all P<0.05];positive staining of COL Ⅰ,COL Ⅲ,and protein expression of FN,ɑ-SMA,and TGF-β1 in lung tissues was significantly decreased[COL Ⅰ(A value):7.09±0.67,8.13±0.64 vs.13.47±1.76,COL Ⅲ(A value):8.19±0.66,8.52±0.22 vs.10.39±0.47,FN protein expression(FN/GAPDH):0.19±0.06,0.24±0.03 vs.0.33±0.02,α-SMA protein expression(α-SMA/GAPDH):0.89±0.41,0.88±0.08 vs.1.78±0.16,TGF-β1 protein expression(TGF-β1/GAPDH):0.04±0.03,0.06±0.01 vs.0.52±0.10,all P<0.05].Metabolomics analysis showed that a total of 10 major differential metabolites were identified between normal control group,model group and JCF group,including arachidonic acid,palmitic acid,indole-3-acetic acid,propionylcarnitine,(S)-4-hydroxymandelonitrile,nalidixic acid,benzocaine,gramine,4-ethylphenol,N-benzylfor mamide.The differential metabolites in silicosis rats reversed by JCF treatment were mainly enriched,including unsaturated fatty acid biosynthesis,arachidonic acid metabolism,tryptophan metabolism,fatty acid elongation,fatty acid degradation and biosynthesis.Conclusion JCF could effectively improve the silicosis fibrosis,which is mainly related to biosynthesis of unsaturated fatty acids biosynthesis,arachidonic acid metabolism,tryptophan metabolism,fatty acid elongation,fatty acid degradation and biosynthesis.
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BACKGROUND: At present, there is short of effective treatment for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). The treatment of IPF with traditional Chinese medicine (TCM) has some advantages. However, the evidence is unclear whether TCM can be recommended as an effective therapy to treat AE-IPF. The purpose of the study is to explore the efficacy and safety of TCM for patients with AE-IPF. METHODS: A randomized, double-blind, placebo-controlled, exploratory clinical trial will be performed. A total of 80 patients diagnosed with AE-IPF will be randomized into the intervention or control group. In addition to conventional treatment, the intervention group will be treated with Kangxianhuanji granule, and the control group will be given a placebo granule. The administration frequency is 10 g each time and two times daily. After 4 weeks of treatment, the patients were followed up for 12 weeks. The primary outcomes are treatment failure rate and all-cause mortality. Secondary outcome measures will include the length of hospitalization, overall survival, acute exacerbation rate, intubation rate, Modified British Medical Research Council (mMRC) score, the St George's Respiratory Questionnaire idiopathic pulmonary fibrosis (SGRQ-I) score, and arterial blood gas analysis. DISCUSSION: TCM may be beneficial in IPF. However, it has never been evaluated in patients with AE-IPF, who are incredibly prone to respiratory failure and have a high mortality rate. It is the first clinical trial to explore the efficacy and safety of TCM in the treatment of AE-IPF. This result will provide a basis for further study, which provides a high-quality evidence for the treatment of AE-IPF with TCM. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900026289 . Registered on 29 September 2019.
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Idiopathic Pulmonary Fibrosis , Medicine, Chinese Traditional , Double-Blind Method , Humans , Idiopathic Pulmonary Fibrosis/diagnosis , Idiopathic Pulmonary Fibrosis/drug therapy , Medicine, Chinese Traditional/adverse effects , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
Objective:To construct the risk prediction model of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and verify its effectiveness based on deep learning and back propagation algorithm neural network (BP neural network).Methods:Based on the relevant data of 1 326 patients with chronic obstructive pulmonary disease (COPD) in the team's previous clinical study, the acute exacerbation, and its risk factors during the stable period and 6 months of follow-up were recorded and analyzed. Combined with previous clinical research data and expert questionnaire results, the independent risk factors of AECOPD after screening and optimization by multivariate Logistic regression including gender, body mass index (BMI) classification, number of acute exacerbation, duration of acute exacerbation and forced expiratory volume in one second (FEV1) were used to build the BP neural network by Python 3.6 programming language and Tensorflow 1.12 deep learning framework. The patients were randomly selected according to the ratio of 4∶1 to generate the training group and the test group, of which, the training group had 1 061 sample data while the test group had 265 pieces of sample data. The training group was used to establish the prediction model of neural network, and the test group was used for back-substitution test. When using the training group data to construct the neural network model, the training group was randomly divided into training set and verification set according to the ratio of 4∶1. There were 849 training samples in the training set and 212 verification samples in the verification set. The optimal model was screened by adjusting the parameters of the neural network and combining the area under the receiver operator characteristic curve (AUC), and the sample data of the test group was substituted into the model for verification.Results:The independent risk factors including gender, BMI classification, number of acute exacerbation, duration of acute exacerbation and FEV1 were collected from the team's previous clinical research, and the AECOPD risk prediction model was constructed based on deep learning and BP neural network. After 10 000 training sessions, the accuracy of the AECOPD risk prediction model in the validation set of the training group was 83.09%. When the number of training times reached 8 000, the accuracy basically tended to be stable and the prediction ability reached the upper limit. The AECOPD risk prediction model trained for 10 000 times was used to predict the risk of the validation set data, and the receiver operator characteristic curve (ROC curve) analysis showed that the AUC was 0.803. When using this model to predict the risk of the data of the test group, the accuracy rate was 81.69%.Conclusion:The risk prediction model based on deep learning and BP neural network has a medium level of prediction efficiency for acute exacerbation within 6 months in COPD patients, which can evaluate the risk of AECOPD and assist the clinic in making accurate treatment decisions.
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Objective:To compare the clinical efficacy of endoscopic resection and laparoscopic surgery in the treatment of gastric gastrointestinal stromal tumor (GIST) with a maximum diameter of 2 to 5 cm, and to analyze the influence of factors such as tumor surface, growth pattern and lesion origin on the choice of resection method, so as to provide a safer and more effective treatment for patients with gastric GIST.Methods:From January 2012 to November 2019, at the First Affiliated Hospital of Zhengzhou University, the clinical data of 301 patients with gastric GIST who underwent endoscopic resection (137 cases in the endoscopic resection group) or laparoscopic surgery (164 cases in the laparoscopic surgery group) were retrospectively analyzed, including age, gender, whether there was depression on the tumor surface (the local subsidence depth of the mucosa on the tumor surface was >5 mm), whether the tumor surface was irregular (non-hemispherical or non-elliptical tumor surface), whether there was combined ulcer, location, shape, origin of the lesion, growth pattern (intralumina growth or combined intraluminal and extraluminal growth), risk classification (very low risk, low risk, medium risk, high risk), whether the tumor was en bloc resection, operation time, whether bleeding or not, fasting time, indwelling time of gastric tube, time of hospitalization, time of postoperative hospital stay, postoperative complications and follow-up. Independent sample t test, chi-square test or Fisher′s exact test and Wilcoxon rank sum test were used for statistical analysis. Results:Among the 137 patients with gastric GIST in the endoscopic resection group, 85 cases (62.0%) underwent endoscopic submucosal dissection, 9 cases (6.6%) underwent endoscopic submucosal excavation, 42 cases (30.7%) underwent endoscopic full-thickness resection, and 1 case (0.7%) underwent submucosal tunnel endoscopic resection. There were no significant differences in gender, age, lesion location, tumor size, and risk classification between the endoscopic resection group and the laparoscopic surgery group (all P>0.05). The tumor surface was depressed, with ulcer or irregular in 1, 49, 26, and 2 cases of patients with gastric GIST of very low risk, low risk, medium risk and high risk, respectively. There was statistically significant difference in the proportion of depression, irregularity and ulcer on the tumor surface at different risk levels ( Z=-2.55, P=0.011). The complete tumor resection rate of the endoscopic resection group was lower than that of the laparoscopic surgery group (86.1%, 118/137 vs. 100.0%, 164/164), and the difference was statistically significant ( χ2=24.28, P<0.001). However the operation time, fasting time, the indwelling time of gastric tube, time of hospitalization, and the time of postoperative hospital stay of the endoscopic resection group were shorter than those of the laparoscopic surgery group, and the total hospitalization cost was lower than that of the laparoscopic surgery group (90.0 min (62.5 min, 150.0 min) vs. 119.5 min, (80.0 min, 154.2 min); 3 d (3 d, 4 d) vs. 5 d (4 d, 7 d); 3 d (2 d, 4 d) vs. 4 d (2 d, 6 d); 11 d (10 d, 14 d) vs. 16 d (12 d, 20 d); 7 d (6 d, 9 d) vs. 9 d (7 d, 11 d); (38 211.6±10 221.0) yuan vs. (59 926.1±17 786.1) yuan), and the differences were statistically significant ( Z=-2.46, -7.12, -4.44, -6.89 and -5.92, t=-13.24; all P<0.05). The incidence of postoperative abdominal pain and other severe postoperative complications (including shock, respiratory failure, pulmonary embolism, gastroparesis, etc.) of the endoscopic resection group were all lower than those of the laparoscopic surgery group (16.8%, 23/137 vs. 27.4%, 45/164; 0.7%, 1/137 vs. 4.9%, 8/164), and the differences were statistically significant ( χ2=4.84, Fisher′s exact test, P=0.028 and 0.043). There were no significant differences in the incidence of intraoperative bleeding, postoperative bleeding, fever and perforation between the two groups (all P>0.05). The incidence of operation-related complications of lesions with intraluminal growth and originating from muscularis propria in the endoscopic resection group were lower than those of the laparoscopic surgery group (19.5%, 25/128 vs. 32.6%, 45/138; 12.6%, 12/95 vs. 31.4%, 37/118), and the differences were statistically significant ( χ2=5.86 and 10.42, P=0.016 and 0.001). There was no significant difference in the postoperative tumor recurrent rate between the endoscopic resection group and the laparoscopic surgery group (0, 0/137 vs. 2.4%, 4/164; Fisher’s exact test, P=0.129). Conclusions:Endoscopic treatment is safe and effective for gastric GIST with a maximum diameter of 2 to 5 cm, which is superior to laparoscopic surgery. However, laparoscopic surgery is recommended for tumor with depressed, ulcerative, or irregular surface and combined intraluminal and extraluminal growth.
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Renal interstitial fibrosis（RIF）is a common pathway for the progression of chronic kidney disease to renal failure，and its pathogenesis is mainly related to renal inflammatory damage，oxidative stress，apoptosis，and excessive extracellular matrix（ECM） deposition. Transforming growth factor-β1（TGF-β1） signaling pathway，mammalian target of rapamycin（mTOR） signaling pathway and other signaling pathways mediate the occurrence and development of RIF. Because of the complicated mechanism of RIF，there have been no specific prevention and treatment measures in clinical practice. Autophagy is a non-damaging response produced by eukaryotic cells. It maintains the balance of tissue homeostasis through degradation and reabsorption. At present， Chinese medicine has achieved desirable clinical effects with its unique advantages of multiple components，multiple effects，and multiple targets in the treatment of chronic kidney disease to delay the process of RIF. Scholars have found that autophagy is consistent with the Yin-Yang theory and the theory of abdominal mass in traditional Chinese medicine （TCM） to a certain extent，and it is involved in many aspects of RIF. The progression of RIF is closely related to autophagy. The targeted therapy of RIF by intervention in autophagy has become the frontier of research. However，little is known about the role of autophagy in RIF and the regulation of autophagy by Chinese medicine in the treatment of RIF. Therefore，it is necessary to further elucidate the relationship between autophagy and RIF in order to clarify the mechanism of autophagy in RIF and the mechanism of Chinese medicine regulating autophagy in targeted therapy of RIF. This article focused on the correlation between autophagy and RIF based on TCM theory，and systematically summarized the role of autophagy in RIF and the intervention of Chinese medicine by combining the effects of autophagy on inflammation damage，oxidative stress，apoptosis，and excessive ECM deposition in RIF， and the regulation mechanism of autophagy in TGF-β1 and mTOR signaling pathways in RIF. This study was expected to provide a certain reference for the clinical treatment of RIF and the development of new drugs.
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Renal interstitial fibrosis（RIF）is a common pathway for the progression of chronic kidney disease to renal failure，and its pathogenesis is mainly related to renal inflammatory damage，oxidative stress，apoptosis，and excessive extracellular matrix（ECM） deposition. Transforming growth factor-β1（TGF-β1） signaling pathway，mammalian target of rapamycin（mTOR） signaling pathway and other signaling pathways mediate the occurrence and development of RIF. Because of the complicated mechanism of RIF，there have been no specific prevention and treatment measures in clinical practice. Autophagy is a non-damaging response produced by eukaryotic cells. It maintains the balance of tissue homeostasis through degradation and reabsorption. At present， Chinese medicine has achieved desirable clinical effects with its unique advantages of multiple components，multiple effects，and multiple targets in the treatment of chronic kidney disease to delay the process of RIF. Scholars have found that autophagy is consistent with the Yin-Yang theory and the theory of abdominal mass in traditional Chinese medicine （TCM） to a certain extent，and it is involved in many aspects of RIF. The progression of RIF is closely related to autophagy. The targeted therapy of RIF by intervention in autophagy has become the frontier of research. However，little is known about the role of autophagy in RIF and the regulation of autophagy by Chinese medicine in the treatment of RIF. Therefore，it is necessary to further elucidate the relationship between autophagy and RIF in order to clarify the mechanism of autophagy in RIF and the mechanism of Chinese medicine regulating autophagy in targeted therapy of RIF. This article focused on the correlation between autophagy and RIF based on TCM theory，and systematically summarized the role of autophagy in RIF and the intervention of Chinese medicine by combining the effects of autophagy on inflammation damage，oxidative stress，apoptosis，and excessive ECM deposition in RIF， and the regulation mechanism of autophagy in TGF-β1 and mTOR signaling pathways in RIF. This study was expected to provide a certain reference for the clinical treatment of RIF and the development of new drugs.
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Chronic renal failure （CRF）， a common outcome of various chronic kidney diseases， is characterized by retention of metabolites and toxins， water-electrolyte imbalance， acid-base disturbance， and various symptoms in diverse systems. The incidence and progression of this disease are influenced by many factors， particularly the change of intestinal flora. Previous research shows that the intestinal flora interacts with CRF. For CRF patients， the metabolic waste fails to be cleared in time due to the gradual decline of renal function and thus accumulates in vivo. Moreover， CRF changes the composition of intestinal flora， damages intestinal barrier， and accelerates the synthesis of intestinal uremic toxins and the accumulation in blood. As a result， the renal injury is aggravated. The imbalance of intestinal flora can induce acute kidney injury， increase cardiovascular complications， stimulate immune inflammatory responses， and thus aggravate the progression of CRF. Microbiota-targeted therapy for CRF has become the research focus. According to traditional Chinese medicine， kidney disease is related to the intestine and kidney disease should be treated from the intestine. Spleen and kidney are in the closest relationship with the pathogenesis of CRF and the intestinal flora. Chinese medicine， which features multiple targets， multiple effects， and multiple components， acts on the "gut-kidney axis". It is thus superior in the clinical treatment of CRF and the regulation of intestinal flora. To be specific， it intervenes in intestinal flora to delay the process of CRF. In this paper， based on the correlation of traditional Chinese medicine theory with intestinal flora and CRF， this paper reviewed the interaction between intestinal flora and CRF and traditional Chinese medicine intervention in the intestinal flora for the treatment of CRF， which is expected to serve as a reference for the clinical treatment of this disease and the drug development.
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Data of 55 cases of gastric neuroendocrine neoplasms (G-NENS) with diameter ≤12 mm in the First Affiliated Hospital of Zhengzhou University from August 2014 to August 2019 were retrospectively analyzed. According to the methods of endoscopic resection, the patients were divided into two groups: the endoscopic mucosal resection with a cap (EMR-C) group (35 cases) and the endoscopic submucosal dissection (ESD) group (20 cases). The results showed that the success rates of operation, the whole resection rates and the complete resection rates were all 100.0% in the two groups. Compared with the ESD group, the EMR-C group had a shorter median operation time (12.00 min VS 28.35 min, P<0.001), less mean hospitalization costs (21 165.19 yuan VS 28 400.35 yuan, P=0.004), and a similar overall incidence of complications [2.86% (1/35) VS 0, P=1.000]. By March 2020, the recurrence rate of EMR-C group and ESD group were 28.6% (10/35) and 15.0% (3/20), respectively, without significant difference ( P=0.418). It is suggested that for G-NENS with diameter ≤12 mm, without muscular invasion, lymph node metastasis or distant metastasis, EMR-C and ESD are both safe and effective, but EMR-C has more advantages in terms of operation time and hospitalization costs.
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Objective:To evaluate the compatibility laws of effective-component compatibility of Bufei Yishen formula Ⅲ (ECC-BYFⅢ) in regulating mucus hypersecretion of chronic obstructive pulmonary disease (COPD).Methods:According to the efficacy of the original Chinese medicine, the components of ECC-BYFⅢ were divided into four categories: Buqi (Ginsenoside Rh1+Astragaloside), Bushen (Icariin), Huatan (Nobiletin), and Huoxue (Paeonol). The four categories were divided into 14 groups based on the method of mathematical permutation. ① The rats were divided into control group, model group, ECC-BYFⅢ, and different components compatibility groups according to the random number table, totaling 17 groups. COPD rat model in stable phase was established by cigarette smoke exposure combined with repeated bacterial infections. The corresponding drugs were given by gavage at the 9th week of modeling, and the samples were collected at the end of the 16th week. The levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloproteinase 1 (TIMP-1) in serum and bronchoalveolar lavage fluid (BALF), and the levels of mucin (MUC) 5AC in lung tissue and BALF were detected by enzyme linked immunosorbent assay (ELISA). ② Human lung epithelial cells BEAS-2B were divided into blank group, model group, and different components compatibility groups. Hypoxia-induced mucus hypersecretion model of human lung epithelial cells BEAS-2B was established 4 hours after corresponding drug pretreatment. The mRNA expressions of MUC5AC, MUC5B, and MUC1 were detected by quantitative polymerase chain reaction (PCR). The mucus secretion indexes of rats and BEAS-2B cells were evaluated by Region (R) value comprehensive evaluation method.Results:① Compared with the control group, MMP-9 in serum and BALF from the model group were significantly increased, the level of TIMP-1 was significantly decreased, and MUC5AC in lung tissue and BALF were significantly increased. The results of R value comprehensive evaluation showed that except for the Buqi and Bushen groups, ECC-BYFⅢ and other components compatibility groups significantly corrected mucus hypersecretion in COPD rats, ECC-BYFⅢ, Bushen Quxie, Fuzheng Huatan, and Quxie groups were much better (R values were 2.15±0.42, 2.11±0.23, 2.16±0.23 and 2.16±0.55, respectively), compared with the model group (R value: 3.00±0.00), the differences were statistically significant (all P < 0.05). ② Compared with the blank group, the mRNA expressions of MUC5AC, MUC5B, and MUC1 increased in the model group. But different components compatibility groups had no significant effects on the mucus secretion of BEAS-2B cells. ③ The comprehensive evaluation results of R value about each in vivo and in vitro index showed that ECC-BYFⅢ, Huoxue, Quxie, Bushen Huoxue, Fuzheng Huatan, Buqi Quxie groups significantly corrected the mucus hypersecretion (R values were 2.30±0.43, 2.33±0.44, 2.12±0.68, 2.27±0.64, 2.24±0.27 and 2.29±0.47, respectively), compared with the model group (R value: 3.00±0.00), the difference was statistically significant (all P < 0.01). The order was: Quxie > Fuzheng Huatan > Bushen Huoxue > Buqi Quxie > ECC-BYFⅢ > Huoxue. Conclusions:Different components compatibility of ECC-BYFⅢ had different effects on COPD mucus secretion. The components containing Huatan (Nobiletin) or Huoxue (Paeonol) showed a better inhibitory effect on mucus secretion.
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Objective:To establish a risk prediction model for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) using regression analysis and verify the model.Methods:The risk factors and acute exacerbation of 1 326 patients with chronic obstructive pulmonary disease (COPD) who entered the stable phase and followed up for 6 months in the four completed multi-center large-sample randomized controlled trials were retrospectively analyzed. Using the conversion-random number generator, about 80% of the 1 326 cases were randomly selected as the model group ( n = 1 074), and about 20% were the verification group ( n = 252). The data from the model group were selected, and Logistic regression analysis was used to screen independent risk factors for AECOPD, and an AECOPD risk prediction model was established; the model group and validation group data were substituted into the model, respectively, and the receiver operating characteristic (ROC) curve was drawn to verify the effectiveness of the risk prediction model in predicting AECOPD. Results:There were no statistically significant differences in general information (gender, smoking status, comorbidities, education level, etc.), body mass index (BMI) classification, lung function [forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), etc.], disease status (the number and duration of acute exacerbation in the past year, duration of disease, etc.), quality of life scale [COPD assessment test (CAT), etc.] and clinical symptoms (cough, chest tightness, etc.) between the model group and the validation group. It showed that the two sets of data had good homogeneity, and the cases in the validation group could be used to verify the effectiveness of the risk prediction model established through the model group data to predict AECOPD. Logistic regression analysis showed that gender [odds ratio ( OR) = 1.679, 95% confidence interval (95% CI) was 1.221-2.308, P = 0.001], BMI classification ( OR = 0.576, 95% CI was 0.331-1.000, P = 0.050), FEV1 ( OR = 0.551, 95% CI was 0.352-0.863, P = 0.009), number of acute exacerbation ( OR = 1.344, 95% CI was 1.245-1.451, P = 0.000) and duration of acute exacerbation ( OR = 1.018, 95% CI was 1.002-1.034, P = 0.024) were independent risk factors for AECOPD. A risk prediction model for AECOPD was constructed based on the results of regression analysis: probability of acute exacerbation ( P) = 1/(1+ e- x), x = -3.274 + 0.518×gender-0.552×BMI classification + 0.296×number of acute exacerbation + 0.018×duration of acute exacerbation-0.596×FEV1. The ROC curve analysis verified that the area under ROC curve (AUC) of the model group was 0.740, the AUC of the verification group was 0.688; the maximum Youden index of the model was 0.371, the corresponding best cut-off value of prediction probability was 0.197, the sensitivity was 80.1%, and the specificity was 57.0%. Conclusion:The AECOPD risk prediction model based on the regression analysis method had a moderate predictive power for the acute exacerbation risk of COPD patients, and could assist clinical diagnosis and treatment decision in a certain degree.