A bibliometric and scientific knowledge map study of the drug therapies for asthma-related study from 1982 to 2021.

Objective: Asthma drug research has been increasing yearly, and its clinical application value has increasingly attracted attention. This study aimed to analyze the development status, research hotspots, research frontiers, and future development trends of the research works on drugs for patients with asthma, especially severe asthma. Methods: Asthma drug-related articles published between 1982 and 2021 were retrieved from the Web of Science Core Collection (WOSCC) database, and only articles published in English were included. CiteSpace and VOSviewer software were utilized to conduct collaborative network analysis of countries/regions, institutions, keywords, and co-citation analysis of references. Results: A total of 3,234 asthma drug-related eligible articles were included. The United States was in a leading position, and Karolinska Institute (Sweden) was the most active institution. The most prolific journal in this field was Journal of Asthma, and the most cited journal was Journal of Allergy and Clinical Immunology. Keyword co-occurrence studies suggested that the current hotspots and frontiers were as follows: ① asthma: fully revealing the potential of existing conventional asthma drugs, determining the best drug delivery system, and indicating the best combination. To continue to explore potential targets for severe asthma or other phenotypes. Inhaled glucocorticoids and budesonide are still one of the important aspects of current asthma drug research and ② severe asthma: the research and development of new drugs, especially monoclonal antibodies including omalizumab, mepolizumab, and benralizumab to improve asthma control and drug safety, have become a research hotspot in recent years, highlighting the importance of "target" selection. Conclusion: This study demonstrates the global research hotspots and trends of the research works on drugs for patients with asthma/severe asthma. It can help scholars quickly understand the current status and hotspots of research in this field.

Drug Therapies for COPD: A Bibliometric Review From 1980 to 2021.

Objective: To analyze all chronic obstructive pulmonary disease (COPD) drugs-related articles that were indexed in the Web of Science Core Collection (WOSCC) database until August 28, 2021 using bibliometric analysis, in order to provide a reliable reference for the treatment of COPD. Methods: A comprehensive search was conducted to analyze all COPD drugs-related articles using WOSCC database from inception to August 28, 2021. Abstracts and potentially eligible articles, which were retrieved during literature search, were screened by two reviewers. Besides, the CiteSpace (5.8.R1) software was utilized to analyze the overall structure of the network, the network clusters, the links between clusters, the key nodes or pivot points, and the pathways. Results: A total of 2552 COPD-drugs related articles were retrieved. From the perspective of categorization of published articles based on country, the United States is the country with the largest number of published articles and completed clinical trials, highlighting the important role of this country in the treatment of COPD. However, in terms of the proportion of ongoing clinical trials, China has the highest proportion, suggesting that China will play a more pivotal role in the medication of COPD in the future. From the perspective of cooperation among countries, the cooperation among European countries was closer than that among Asian countries. In the recent three decades, the top 20 institutions, with a particular concentration on the treatment of COPD, were from North America and Europe. The co-citation analysis showed that, among 2,552 articles, 53154 citations were recorded, and the co-citation network indicated that 24 clusters could be achieved. Conclusion: The administration of bronchodilators and pulmonary drug delivery systems, as well as consideration of elderly COPD patients remained the hotspots, while triple therapy and comorbidity of COPD, as well as the prevention and treatment of elderly COPD patients had been frontiers in recent years.

Traditional Chinese medicine tonifying kidney therapy (Bu shen) for stable chronic obstructive pulmonary disease: Protocol for a systematic review and meta-analysis.

BACKGROUND: Traditional Chinese medicine (TCM) is commonly used to combine with pharmacotherapy for stable chronic obstructive pulmonary disease (COPD) in China and other Asian countries such as South Korea and Japan. The objective of this systematic review is to evaluate the efficacy and safety of tonifying kidney therapy (Bushen, TK) for stable COPD. METHODS: Randomized controlled trials (RCTs) of TK for stable COPD were searched from 4 databases including Pubmed, the Cochrane library, CBM (China Biology Medicine disc, CBMdisc), CNKI (China National Knowledge Infrastructure) from inception to December 2017. Two reviewers independently screened the literature, extracted the data and assessed the risk of bias in included studies. RevMan 5.3 software was used for meta-analysis. The primary outcomes analyzed in this meta-analysis were effectiveness, TCM Syndrome Score, dyspnea (modified Medical Research Council questionnaire [mMRC]), COPD health status (COPD Assessment Test [CAT]), exercise capacity (6-min walk distance in meters [6mWD]), and respiratory-specific quality of life (St George's Respiratory Questionnaire [SGRQ]). Second outcomes analyzed for this meta-analysis were lung function (forced expiratory volume in 1 second [FEV1], FEV1%, forced vital capacity [FVC], FEV1/FVC), the frequency of acute exacerbation, T-lymphocyte subsets (CD4, CD8, CD4/CD8), and immunoglobulin (IgA, IgG, and IgM). The summary results will be pooled using the random-effects model or fixed-effects model according to the heterogeneity of the included studies. RESULT: This systematic review will provide an evidence of TK for stable COPD, and will submit to a peer-reviewed journal for publication. CONCLUSION: The conclusion of this systematic review will provide evidence to judge whether TK is an effective intervention for stable COPD patients. PROSPERO REGISTRATION NUMBER: PROSPERO CRD 42018090328.

Inhibitory effect of paeoniflorin on inflammatory chemokines and their receptor in a mouse model of asthma / 中国实验动物学报

Objective To study the effect of paeoniflorin on inflammatory chemokines and their receptor in a rat model of ovalbumin-induced asthma.Methods Sixty 6-week old SPF female BALB/c mice were used in this study.To es-tablish a mouse model of asthma by sensitizing and challenging with ovalbumin.ELISA was used to analyze the serum IL-6 and TNF-α, and the specific IgE against ovalbumin ( OVA-IgE ) , CCL19 and CCL21 in bronchoalveolar lavage fluid (BALF).RT-PCR was performed to determine CCR7mRNA and protein expression of chemokine receptor CCR7, and the level of NF-κB was tested by Western blot.ResultsIn In the paeoniflorin groups, the serum IL-6 and TNF-αlevels were significantly lower, and the OVA-IgE, CCL19 and CCL21 levels in BALF were significantly reduced, compared with that in the control group.CCR7mRNA and protein expression of chemokine receptor CCR7 and NF-κB in the lung were significant-ly reduced by paeoniflorin.Conclusions Paeoniflorin has a remarkably inhibitory effect on the airway inflammatory chemo-kines CCL19/CCL21 and the receptor CCR7 in the mouse model of asthma.

Interventional effect of cisplatin combined with fluoxetine on mice bearing Lewis lung cancer with depression / 中国实验动物学报

Objective To observe if fluoxetine has a potency to inhibit the progression of Lewis lung cancer by combining the fluoxetine and cisplatin to treat the mice bearing Lewis lung cancer with depression .Methods We devel-oped a mouse model of Lewis lung cancer with depression which was intervened with cisplatin and fluoxetine , and the indi-cators related to cancer and depression were tested .Social interaction test was used to measure the behavioral changes of the depressed model mice .The serum cortisol and IL-6, BDNF mRNA in the hippocampus , and NF-κB and VEGF in the tumor tissue were selected for investigation and comparison .Results The mice which were induced by social defeat exhib-ited social avoidance behavior in the social interaction test .The cortisol and IL-6 level in both combination groups was de-creased compared with that in the model group (P0.05).Conclusions Fluoxetine has antidepres-sant effect by decreasing the high level of serum cortisol and promoting the BDNF mRNA expression in the hippocampus . However , fluoxetine is not found to have the potency to inhibit the expression of NF -κB related with the progression of tumor.

Comparison of effect of granules and herbs of Bu-Shen-Yi-Qi-Tang on airway inflammation in asthmatic mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bu-Shen-Yi-Qi-Tang (BSYQT), which is prescribed on the basis of clinical experience, is commonly used in clinics of traditional Chinese medicine (TCM) for asthma treatment. The components of BSYQT include Radix Astragali (RA), Herba Epimedii (HE) and Radix Rehmanniae (RR). The aim of this study was to compare the effect of granules and herbs of BSYQT on airway inflammation in asthmatic mice.</p><p><b>METHODS</b>Sixty female BALB/c mice were randomly divided into the normal control (NC) group, asthmatic group (A), decoction of granules of BSYQT treatment group (GD), decoction of herbs of BSYQT treatment group (HD), and dexamethasone treatment group (DEX). The mouse asthmatic model was induced by ovalbumin (OVA) sensitization and challenge. GD and HD of BSYQT as well as DEX were prepared and administered by intragastric infusion. Airway hyperresponsiveness (AHR) to methacholine (Mch), lung histopathology analysis, inflammatory mediators in serum (IL-4, IL-5, IL-17A, IFN-γ, and eotaxin) and in lung (IL-4, IL-5, IFN-γ, and eotaxin) were selected for investigation and comparison.</p><p><b>RESULTS</b>Both GD and HD treatment could decrease airway resistance (RL) and increase dynamic compliance (Cdyn) to Mch compared with the A group (P < 0.05). HD treatment was more effective in RL reduction than Mch at doses of 3.125 and 6.25 mg/ml (P < 0.05) and in Cdyn increase at Mch doses of 6.25 and 12.5 mg/ml (P < 0.05). There were no marked differences in RL reduction and Cdyn improvement between mice in HD and DEX groups (P > 0.05). Both GD and HD treatment markedly attenuated lung inflammation (P < 0.05), and HD treatment demonstrated more significant therapeutic function in alleviating lung inflammation than that of GD and DEX treatment (P < 0.05). Both GD and HD treatment resulted in a significant reduction in IL-4 and IL-17A levels and an increase in the IFN-γ level in serum compared with the A group (P < 0.05). The effect of HD in lowering the IL-4 and IL-17A level was significantly greater than that of GD (P < 0.05), and was not significantly different from DEX (P > 0.05). HD treatment significantly reduced the serum level of IL-5 and eotaxin compared with the A group (P < 0.05), however, mice in the GD treatment group did not demonstrate this effect. GD and HD treatment significantly reduced IL-4 and eotaxin mRNA expression compared with the A group (P < 0.05). HD treatment significantly reduced IL-5 mRNA expression compared with the A group (P < 0.05). There was a significant difference between the GD and HD treatment groups in reducing IL-5 and eotaxin mRNA expression (P < 0.05). HD treatment was more effective in down-regulation of IL-5 in serum and eotaxin level both in serum and lung than DEX (P < 0.05). Compared with the A group, an obvious increase in mRNA expression of IFN-γ was observed in both the GD and HD treatment groups (P < 0.05). However, the effect of HD treatment on increase of IFN-γ mRNA expression was more apparent than GD and DEX treatment (P < 0.05).</p><p><b>CONCLUSIONS</b>Both GD and HD treatment could decrease AHR, attenuate lung inflammation, reduce IL-4, IL-5, IL-17A, and eotaxin levels and increase IFN-γ levels in asthmatic mice. HD treatment manifests more remarkable inhibitory effects on asthmatic inflammation than GD treatment, which could provide a guide for further research on the screening of the material basis of the best anti-inflammatory effect of BSYQT.</p>

The role of oxidative stress induced histone modification in chronic obstructive pulmonary disease / 医学研究生学报

Chronic obstructive pulmonary disease ( COPD) is a prevalent disease which is the fourth leading cause of death worldwide and will be the major economic burden of diseases according to the World Bank /World Health Organization .However , the pathogenesis of COPD is inadequately understood , oxidative stress and chronic inflammation are considered to be two independent path -ogenetic factors , but the epigenetic put them together because of changes of the environment lead to gene abnormal expression .This ar-ticle summarizes the relationship between histone modifications of genes induced by oxidative stress and the inflammation , antioxidant response, apoptosis, autophagy and the differentiation of T cell subsets in the pathogenesis of COPD .The work will provide more choices for clinical treatment of COPD .

Clinical research of individualized therapy in advanced non-small cell lung cancer guiding by & nbsp;detection of ERCC1 protein / 中国癌症杂志

10.3969/j.issn.1007-3969.2013.05.002

Baicalin attenuates inflammation by inhibiting NF-kappaB activation in cigarette smoke induced inflammatory models.

Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) is a key player in the inflammatory response. Baicalin is an extract from roots of the plant scutellaria baicalensis. Many studies show that baicalin has anti-inflammatory, anti-bacterial and antiviral activities. Here we investigated the influence of baicalin on COPD inflammation and the mechanism of anti-inflammatory effect in vivo and in vitro. In vivo, COPD rat model was established by cigarette smoke (CS) exposure. Thirty-six Sprague-Dawley (SD) rats were randomly assigned to six experimental groups: control, CS, dexamethasone (DXM), and baicalin (20 mg/kg, 40 mg/kg, 80 mg/kg). The lung pathology was observed and leukocytes in bronchoalveolar lavage fluid (BALF) were counted by Optical microscope. Pulmonary function was measured by using an animal plethysmograph. The production of cytokines was measured by ELISA and the expression levels of NF-kappaB p65 protein were detected by immunohistochemistry. The results in vivo show CS exposure significantly increased the expression of IL-8, IL-6 and TNF-alpha in plasma and BALF and enhanced NF-kappaB p65 expression in the lungs. Baicalin treatment markedly attenuated the inflammatory effects of CS. In vitro, cell model was established by using cigarette smoke extract (CSE) to stimulate type II pneumocytes. Type II pneumocytes were also divided into six groups: control, CSE, pyrrolidine dithiocarbamate (PDTC), and baicalin (5 mumol, 10 mumol, 20 mumol). Cytokines levels were measured by ELISA. Expression of IkappaB and p65 phosphorylation was detected by western blotting. NF-kappaB DNA-binding activity was detected by EMSA. The results show that CSE resulted in increasing IL-8, IL-6 and TNF-alpha expression and activation of NF-kappaB. The proinflammatory effects of CSE were inhibited by treatment of baicalin in a dose-dependent manner. It can be concluded that baicalin has significant anti-inflammatory effects on CS induced COPD rat models and CSE-induced cell models, and the effectiveness increases with increasing baicalin dosage. The anti-inflammatory effect is likely achieved by inhibiting the NF-kappaB pathway.

Optimal combination of baicalin, icariin and Astragalus saponin I from a Chinese herbal compound Biminne / 中西医结合学报

Objective: To study the optimal combined ratio of baicalin, icariin and Astragalus saponin I from a Chinese herbal compound Biminne. Methods: Firstly, a mouse model of allergic rhinitis was established by intraperitoneal injection of ovalbumin (OVA) and aluminum hydroxide gel suspension, and the effective dose range of baicalin, icariin and Astragalus saponin I was detected by 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt method. Secondly, 10 groups of combinations of baicalin, icariin and Astragalus saponin I assembled by U*(10)(10(8)) form were employed to determine the optimal combination by means of analyzing of the inhibitory effect on the splenocyte proliferation. Finally, the effects of each effective ingredient and the optimal combination were compared by observing the splenocyte proliferation, the contents of interleukin-4 (IL-4), IL-5, interferon-gamma (IFN-gamma) in supernatant of the splenocyte cultures and the ratio of IL-4 to IFN-gamma in order to verify the result. Results: Baicalin or icariin at concentrations ranging from 2 to 10 mumol/L, and Astragalus saponin I from 1 to 10 mumol/L effectively suppressed the splenocyte proliferation. When the proportion of baicalin, icariin and Astragalus saponin I was 1:2.14:2.65, the inhibitory effect was most remarkable. Further research confirmed the rationality of the optimal combination. Conclusion: An optimal combination of the major effective ingredients from Chinese herbal compound Biminne most effectively suppresses the proliferation of splenocytes from sensitized mice and regulates the cytokine secreting.

Effect of Ad-Gax transfection on apoptosis of human lung adenocarcinoma A549 cells and its mechanism / 中国肺癌杂志

<p><b>BACKGROUND</b>Apoptosis is closely related to development of lung cancer. It is a strategy of lung cancer therapy to induce apoptosis. The aim of this study is to explore the effects of growth arrest-specific homeobox (Gax) transfection on apoptosis and expression of Bcl-2 and Bax proteins of human lung adenocarcinoma A549 cells.</p><p><b>METHODS</b>A549 cells were transfected with Gax gene by a replication-deficient adenovirus expressing the hemagglutinin-tagged Gax cDNA (Ad-Gax). Apoptosis of A549 cells was observed by transmission electronic microscope and terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) positive staining. Apoptotic rate of A549 cells was evaluated by flow cytometry. Expressions of Bcl-2 and Bax proteins in A549 cells were detected by immunocytochemistry.</p><p><b>RESULTS</b>Before Ad-Gax transfection, none or few of TUNEL-positive A549 cells were detected. After Ad-Gax transfection, a marked increase in TUNEL-positive staining occurred, especially at 24 h later. The ratio of apoptosis of A549 cellsin non-transfection group and transfection groups at 12 h, 24 h, 48 h were 0.25%, 12.57%, 17.29%, 15.03%, respectively. Compared with non-transfection group, the apoptotic rates of transfection groups increased significantly (Chi-square value was 7.357, 11.126 and 9.943 respectively, P < 0.01). The average optical density (AOD) of Bcl-2 protein in A549 cells in non-transfection group and transfection groups at 12 h, 24 h, 48 h were 2.02±0.07, 1.79±0.02, 1.25±0.51 and 1.21±0.24 respectively. Compared with non-transfection group, AOD of Bcl-2 protein in A549 cells in transfection groups decreased significantly (t value was 6.651, 7.089 and 7.438 respectively, P < 0.01). On the other hand, Bax protein expression in transfection groups increased, the AODs of Bax were 4.49±0.61, 4.24±0.37 and 3.95±0.43, respectively. Compared with non-transfection group (3.12±0.42), AOD of Bax protein in A549 celle in transfection groups increased significantly (t value was 7.469, 7.287 and 6.473 respectively, P < 0.01). In the Ad-Gax transfection groups the lower Bcl-2/Bax ratio was, the higher the apoptotic rate of A549 cells was (r=-0.49, P < 0.01).</p><p><b>CONCLUSIONS</b>Ad-Gax transfection can induce A549 cells apoptosis. Possible mechanism is that Gax can downregulate Bcl-2 protein expression and upregulate Bax protein expression, and A549 cells apoptosis is related to the Bcl-2/Bax ratio.</p>