Molecular mechanism of Jianpiyifei II granules in the treatment of chronic obstructive pulmonary disease: Network pharmacology analysis, molecular docking, and experimental assessment.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is defined by persistent airway and lung inflammation, excessive mucus production, remodeling of the airways, and damage to the alveolar tissue. Based on clinical experience, it has been observed that Jianpiyifei II (JPYF II) granules exhibit a significant therapeutic impact on individuals suffering from stable COPD. Nevertheless, the complete understanding of JPYF II's potential mode of action against COPD remains to be further clarified. PURPOSE: To further investigate the underlying mechanism of JPYF II for treating COPD and clarify the role of the IL-17 pathway in the treatment. METHODS: A variety of databases were utilized to acquire JPYF II's bioactive components, as well as related targets of JPYF II and COPD. Cytoscape was utilized to establish multiple interaction networks for the purpose of topological analyses and core-target screening. The Metascape was utilized to identify the function of target genes and crucial signaling pathways. To evaluate the interactions between bioactive ingredients and central target proteins, molecular docking simulations were conducted. Following that, a sequence of experiments was conducted both in the laboratory and in living organisms, which included analyzing the cell counts in bronchoalveolar lavage fluid (BALF), examining lung tissue for histopathological changes, conducting immunohistochemistry, RT‒qPCR, ELISA, and Western blotting. RESULTS: In JPYF II, 88 bioactive ingredients were predicted to have a total of 342 targets. After conducting Venn analysis, it was discovered that 284 potential targets of JPYF II were linked to the provision of defensive benefits against COPD. The PPI network yielded a total of twenty-four core targets. The findings from the analysis of enrichment and gene‒pathway network suggested that JPYF II targeted Hsp90, MAPKs, ERK, AP-1, TNF-α, IL-6, COX-2, CXCL8, and MMP-9 as crucial elements for COPD treatment through the IL-17 pathway. Additionally, JPYF II might modulate MAPK signaling pathways and the downstream transcription factor AP-1 via IL-17 regulation. According to the findings from molecular docking, it was observed that the 24 core target proteins exhibited robust binding affinities towards the top 10 bioactive compounds. Furthermore, the treatment of COPD through the regulation of MAPKs in the IL-17 pathway was significantly influenced by flavonoids and sterols found in JPYF II. In vitro, these observations were further confirmed. In vivo results demonstrated that JPYF II reduced inflammatory cell infiltration in pulmonary tissues and the quantity of inflammatory cells in BALF obtained from LPS- and CS-stimulated mice. Moreover, the administration of JPYF II resulted in the inhibition of IL-17 mRNA and protein levels, phosphorylation levels of MAPK proteins, and expression of phosphorylated AP-1 proteins. It also suppressed the expression of downstream effector genes and proteins associated with the IL-17/MAPK/AP-1 signaling axis in lung tissues and BALF. CONCLUSION: This research reveals that JPYF II improves COPD by controlling the IL-17/MAPK/AP-1 signaling axis within the IL-17 pathway for the first time. These findings offer potential approaches for the creation of novel medications that specifically target IL-17 and proteins involved in the IL-17 pathway to address COPD.

Efficacy and Safety of Chinese Medicine Resuscitation Pack for Enhanced Recovery after Bronchoscopy: A Randomized, Single-Blind, Placebo-Controlled Clinical Trial.

OBJECTIVE: To evaluate the efficacy and safety of a hospital-made resuscitation pack, a Chinese medicinal herbal compound formula designed to enhance recovery in post-bronchoscopy patients. METHODS: In this randomized, single-blind, placebo-controlled clinical trial, eligible patients were randomly assigned 1:1 to either the treatment or control groups. The patients in the treatment group applied the resuscitation pack, which contained aromatic compounded Chinese herbs. The patients in the control group applied a hospital-made, single herb placebo pack. Packs were placed on the Tiantu (CV 22) acupuncture point for 4 h as soon as the bronchoscopy finished. Efficacy indicators, such as recovery time, patients' symptoms including nausea and dizziness, and adverse events (AEs) were observed and compared. The outcome indices were evaluated at baseline, 1 and 24 h after the bronchoscopy. Subgroup analysis was further performed by patients' age and depth of sedation. RESULTS: When applying generalized estimating equations (GEE) to evaluate the intensity of post-bronchoscopy nausea and vomiting, the intensity was lower in the treatment group (163 cases) compared with the control group (162 cases; 95% CI: 0.004, 0.099, P=0.03]. Also, significantly lower intensity of nausea was observed in the 60-70 years of age subgroup (95% CI: 0.029, 0.169, P=0.006) and deep sedation subgroup (95% CI: 0.002, 0.124; P=0.04). There was no significant difference in dizziness between two groups by GEE (95% CI: -0.134, 0.297; P=0.459). In addition, no serious AEs were observed in either group. CONCLUSIONS: Our study found that the resuscitation pack markedly improved patients' symptoms by reducing nausea and vomiting after bronchoscopy without AEs, compared with placebo in the perioperative period. (Trial registration No. ChiCTR2000038299).

Effectiveness and safety of Xingbei Zhike granules in patients with postinfectious cough: A multicenter, randomized, double-blinded, placebo-controlled trial.

BACKGROUND: Postinfectious cough (PIC) is a common symptom following a respiratory tract infection. Xingbei Zhike (XBZK) granules, a Chinese patent medicine, has been widely used for PIC in clinics. However, there is a lack of evidence on the effectiveness. PURPOSE: To investigate whether treatment with XBZK granules is effective for PIC. STUDY DESIGN: A multicenter, randomized, double-blinded, placebo-controlled trial. METHODS: Eligible participants from fourteen hospitals were randomly assigned in 3:1 ratio to receive either XBZK granules or placebo for 14 days. The primary outcome was the area under the curve (AUC) of a visual analogue scale (VAS) for cough symptoms. Secondary outcomes included cough symptom score (CSS), time and probability of recovery from cough, traditional Chinese medicine (TCM) syndrome score, relief rates of individual symptoms, Leicester Cough Questionnaire (LCQ) score, and the use of reliever drug. RESULTS: A total of 235 patients (176 in XBZK and 59 in placebo groups) were included in the analysis. The AUC for cough VAS scores was lower in the XBZK than placebo group (-8.10, 95 % CI -14.12 to -2.07, p = 0.009), indicating superiority. XBZK decreased CSS (-0.68 points, 95 % CI -1.13 to -0.22, p = 0.01), shortened time to cough recovery (-2 days, hazard ratio [HR] 1.48, 95 % CI 1.03 to 2.13, p = 0.02), enhanced the probability of cough recovery (risk ratio [RR] 1.66, 95 % CI 1.07 to 2.58, p = 0.03), lowered TCM syndrome score (-0.99 points, 95 % CI -1.58 to -0.40, p = 0.004), increased the rate of daytime (RR 1.84, 95 % CI 1.07 to 3.15, p = 0.02) and nighttime (RR 2.07, 95 % CI 1.29 to 3.35, p = 0.004) cough recovery, and reduced the viscosity of sputum (RR 2.92, 95 % CI 1.66 to 5.13, p < 0.001) compared to placebo. There were no significant differences in LCQ scores and taking reliever drugs between groups. No severe adverse events were reported in either group. CONCLUSIONS: XBZK granules are a promising therapy against PIC, effective in lowering the overall severity of cough, shortening the time to cough recovery, and reducing the viscosity of sputum.

The Role of Acupoint Application of Herbal Medicine for Asthma: Meta-Analysis of Randomized Double-Blind Placebo-Controlled Trials.

Background: Acupoint application of herbal medicine (AAHM) has been widely used in China. At present, there is no systematic review of AAHM versus placebo in the treatment of asthma. This systematic review aims to assess the efficacy of AAHM for asthma. Methods: Searches were conducted in five English databases and four Chinese databases from their inceptions until December 2020. Randomized double-blind placebo-controlled trials were screened, and included studies evaluated routine pharmacotherapy (RP) plus AAHM versus RP plus placebo or AAHM versus placebo. The Cochrane risk of bias tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were performed to evaluate the methodological quality and quality of evidence separately. Results: Sixteen studies involving 1,730 participants were included in this review. Compared with placebo plus RP, participants receiving long-term AAHM plus RP showed improvement in asthma quality of life questionnaire (AQLQ) with moderate-quality evidence (MD 6.53 points, 95% CI 2.70 to 10.36). Low-quality evidence indicated that AAHM plus RP was associated with improved FEV1 (%) compared with placebo plus RP, whether long- or short-term use (MD 11.80%, 95% CI 2.84 to 20.76; MD 10.57%, 95% CI 8.40 to 12.74; respectively). Moderate-quality evidence showed that participants receiving short-term AAHM were associated with a higher AQLQ score (MD 6.57 points, 95% CI 3.76 to 9.38) and a lower frequency of acute exacerbations (MD -1.84, 95% CI -2.32 to -1.36) compared with placebo. Low-quality evidence also indicated that AAHM was associated with improved FEV1 (L) compared with placebo, whether long- or short-term use (MD 0.35 litres, 95% CI 0.03 to 0.67; MD 0.66 litres, 95% CI 0.59 to 0.73; respectively). Conclusions: Moderate-quality evidence is promising that AAHM can improve the quality of life and reduce acute exacerbations in patients with asthma. AAHM also shows a positive role in improving lung function, but the evidence is so indefinite due to low quality.

Treatment with JianPiYiFei II granules for patients with moderate to very severe chronic obstructive pulmonary disease: A 52-week randomised, double-blinded, placebo-controlled, multicentre trial.

BACKGROUND: Complementary and alternative therapy is widely used to treat chronic obstructive pulmonary disease (COPD). A Chinese herbal medicine, JianPiYiFei (JPYF) II granules, have been shown to improve COPD patients' quality of life, however long-term effectiveness has not been examined. PURPOSE: To investigate whether long-term treatment with JPYF II granules is effective and safe for patients with stable, moderate to very severe COPD. STUDY DESIGN AND METHODS: A multicentre, randomised, double-blinded, placebo-controlled trial was conducted. Eligible participants from six hospitals were randomly assigned 1:1 to receive either JPYF II granules or placebo for 52 weeks. The primary outcome was the change in St. George's Respiratory Questionnaire (SGRQ) score during treatment. Secondary outcomes included the frequency of acute exacerbations during treatment, COPD Assessment Test (CAT), 6-minute walking test (6MWT), lung function, body mass index, airflow obstruction, dyspnoea, exercise capacity (BODE) index, and peripheral capillary oxygen saturation (SpO2) at the end of treatment. RESULTS: A total of 276 patients (138 in each group) were included in the analysis. JPYF II granules led to a significantly greater reduction in SGRQ score (-7.33 points, 95% CI -10.59 to -4.07; p < 0.0001) which reflects improved quality of life. JPYF II granules improved CAT (-3.49 points, 95% CI -5.12 to -1.86; p < 0.0001) and 6MWT (45.61 metres, 95% CI 20.26 to 70.95; p = 0.0005), compared with placebo. Acute exacerbations were less frequent with JPYF II granules than with placebo (0.87 vs. 1.34 events per patient; p = 0.0043). There were no significant differences between the groups in lung function, BODE index and SpO2. JPYF II granules were well tolerated and no significant adverse effects were noted. CONCLUSIONS: Long-term treatment with JPYF II granules is effective in moderate to very severe COPD, improving quality of life and exercise capacity, decreasing the risk of acute exacerbation, and relieving symptoms.

Inhibition of Inflammation and Regulation of AQPs/ENaCs/Na+-K+-ATPase Mediated Alveolar Fluid Transport by Total Flavonoids Extracted From Nervilia fordii in Lipopolysaccharide-induced Acute Lung Injury.

Aims: The occurrence of vascular permeability pulmonary edema in acute lung injury (ALI) is related to the imbalance of alveolar fluid transport. Regulating the active transport of alveolar fluid by aquaporins (AQPs), epithelial sodium channels (ENaCs), and Na+-K+-ATPase can effectively reduce the edema fluid in the alveolar cavity and protect against ALI. We evaluated the therapeutic effects of total flavonoids, extracted from Nervilia fordii (TFENF), and investigated its potential mechanisms of alveolar fluid transport in a rat ALI model. Materials and methods: A model of lipopolysaccharide (LPS, 5 mg/kg)-induced ALI was established in Sprague-Dawley (SD) rats through the arteriae dorsalis penis. SD rats were divided into six groups, including the vehicle, LPS model, TFENF (6 mg/kg, 12 mg/kg, 24 mg/kg), and dexamethasone group (DEX group, 5 mg/kg). The wet-to-dry (W/D) lung weight ratio, oxygenation index, and histopathological observation were used to evaluate the therapeutic effect of TFENF. The mRNA expression of AQPs, ENaCs, and pro-inflammatory cytokines was determined using real-time polymerase chain reaction, whereas protein expression was determined using immunohistochemistry. The Na + -K + -ATPase activity was assessed using enzyme-linked immunosorbent assay. Results: LPS significantly stimulated the production of inflammatory mediators including tumor necrosis factor (TNF)-α and interleukin (IL)-1ß, and disrupted the water transport balance in the alveolar cavity by inhibiting AQPs/ENaCs/Na + -K + -ATPase. Pretreatment with TFENF reduced the pathological damage and W/D ratio of the lungs and ameliorated the arterial blood oxygen partial pressure (PaO2) and oxygenation index. TFENF further decreased the mRNA level of TNF-α and IL-1ß; increased the expression of AQP-1, AQP-5, αENaC, and ßENaC; and increased Na + -K + -ATPase activity. Moreover, the regulation of AQPs, ßENaC, and Na + -K + -ATPase and the inhibition of TNF-α and IL-1ß by TFENF were found to be dose dependent. Conclusion: TFENF protects against LPS-induced ALI, at least in part, through the suppression of inflammatory cytokines and regulation of the active transport capacity of AQPs/ENaCs/Na + -K + -ATPase. These findings suggest the therapeutic potential of TFENF as phytomedicine to treat inflammation and pulmonary edema in ALI.

Immunosuppression Induced by Glutamine Deprivation Occurs via Activating PD-L1 Transcription in Bladder Cancer.

Few studies have reported whether nutrients in the tumor microenvironment can regulate the expression of PD-L1. Since tumor cells are often situated in a low-glutamine environment, we investigated PD-L1 expression under glutamine deprivation in bladder cancer cells. PD-L1 expression and the activation of the EGFR/MEK/ERK/c-Jun signaling pathway under glutamine deprivation were investigated by qPCR, Western blot, and immunofluorescence analyses. C-Jun-mediated transcriptional regulation of the PD-L1 gene was assessed by ChIP. PD-L1 expression and activation of the EGFR/MEK/ERK/c-Jun signaling pathway were assessed in T24 cells, TCCSUP cells and BALB/c mice with or without glutamine supplementation. Additionally, the impact of PD-L1 expression under glutamine deprivation on the function of T cells was investigated by ELISA. The expression of PD-L1 and EGFR/MEK/ERK/c-Jun pathway activation were elevated by glutamine deprivation, and c-Jun was enriched in the enhancer region of PD-L1. The expression of PD-L1 was considerably impaired by inhibiting the EGFR/MEK/ERK/c-Jun pathway and was elevated by activating this signaling pathway. In addition, the elevated PD-L1 expression and MEK/ERK/c-Jun signaling pathway activation were reduced by glutamine supplementation in vitro and in vivo. PD-L1 upregulation by glutamine deprivation in bladder cancer cells could reduce IFN-γ production by T cells. The expression of PD-L1 was upregulated under glutamine deprivation through the EGFR/MEK/ERK/c-Jun pathway to impair T cell function.

The ethnopharmacology, phytochemistry, pharmacology and toxicology of the genus Erycibe (Convolvulaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Erycibe belongs to the Convolvulaceae family that contains approximately 70 species mainly distributed from tropical and subtropical Asia to north of Australia. Several Erycibe species are traditionally used in folk medicine for the treatment of various ailments, including rheumatic arthralgia, primary glaucoma, hepatopathies, and infectious and malignant diseases. AIM OF THE REVIEW: This review aims to summarize comprehensive and updated information on traditional medicinal uses, phytochemistry, pharmacology, and toxicology of Erycibe species to provide a reference for the further research and application of the Erycibe genus. MATERIALS AND METHODS: The scientific and extensive literatures between 1975 and 2020 were systematically gathered from scientific databases such as SciFinder Scholar, Science Direct, Web of Science, PubMed, Google Scholar, Scopus, Springer Link and China National Knowledge Infrastructure (CNKI), as well as Chinese herbal classic books, PhD and MSc theses, and several official websites. RESULTS: Erycibe species have been used for the treatment of various rheumatoid diseases, glaucoma, a variety of hepatic diseases, infectious diseases and various malignancies in the traditional and local medicine. Since the 1970s, 153 compounds, including coumarins, quinic acid derivatives, flavonoids, alkaloids, lignans, and others have been isolated from five species of the Erycibe genus. Pharmacological studies have shown that these extracts and compounds from the Erycibe genus have extensive activities consistent with the traditional and local applications, such as anti-glaucoma, anti-arthritic, hepatoprotective and anti-cancer activities, as well as anti-inflammatory, anti-respiratory syncytial virus (RSV), and neuroprotective properties. CONCLUSIONS: Although there are extensive data on the genus Erycibe, certain specific gaps still exist. For herbal preparations containing Erycibe species, clinical toxicological investigation is required for the safety of these herbal preparation therapies, as well as further investigations on pharmacokinetics and bioavailability for guideline for clinical application. Furthermore, more detailed pharmacological, toxicological and clinical researches are needed to assess the alternatives to Erycibe species. Systematic and comprehensive pre-clinical studies are similarly required to estimate the possibility of extracts and compounds from the genus Erycibe with bioactivity developing into new drugs.

Herbal Medicine for Adult Patients with Cough Variant Asthma: A Systematic Review and Meta-Analysis.

INTRODUCTION: Herbal medicine is commonly used by patients with chronic cough, but the role of herbal medicine for cough variant asthma (CVA) has not yet been clearly defined. For the first time, we performed a meta-analysis to integrate the current evidence of randomized controlled trials (RCTs) on this topic and assess the efficacy of herbal medicine in adults with CVA. METHODS: A comprehensive search was conducted in electronic databases to identify RCTs of herbal medicine for adult CVA. Cochrane systematic review methods were followed, and the Grading of Recommendations Assessment, Development, and Evaluation was performed to evaluate the quality of evidence. RESULTS: Twenty-eight RCTs were included. Compared with placebo, moderate-quality evidence from two studies showed that herbal medicine was associated with reduced cough symptom score (CSS) (MD -1.15 points; 95% CI, -1.67 to -0.63) and visual analogue scale (VAS) (MD -1.76 points; 95% CI, -2.66 to -0.86). Compared with montelukast, low- to moderate-quality evidence from 11 studies indicated that herbal medicine was associated with improved Leicester Cough Questionnaire (LCQ) (MD 2.38 points; 95% CI, 1.32 to 3.44), reduced CSS (SMD -0.81 points; 95% CI, -1.09 to -0.53), and VAS (MD -1.34 points; 95% CI, -1.82 to -0.86). There were no significant differences between herbal medicine and ICS plus bronchodilator. CONCLUSIONS: In adults with CVA, herbal medicine may result in improved quality of life and reduced cough frequency and severity scores compared with placebo or montelukast. Herbal medicine was not better than ICS plus a bronchodilator but the evidence is very uncertain.

Clinical practice guideline on treating influenza in adult patients with Chinese patent medicines

Influenza is a major public health problem worldwide. Mutations and resistance development make the use of antiviral therapy challenging. Chinese patent medicines are often used to treat influenza in China and well tolerable. However, the misuse of Chinese patent medicines is common. We therefore aimed to develop an evidence-based guideline on treating influenza with Chinese patent medicines in adults to guide clinical practice. We formed a steering committee, a consensus panel, a consultants' group and an evidence synthesis team to guide the development of the guideline. We formulated the clinical questions through two rounds of survey, and finally selected five questions. We then systematically searched the related evidence and conducted meta-analyses, evidence summaries and GRADE decision tables to draft the recommendations, which the consensus panel then voted on using the Delphi method. Finally, we formulated six recommendations based on the evidence synthesis and experts' consensus. For treating mild influenza, we suggest either Lianhua Qingwen capsule, Jinhua Qinggan granule, Banlangen granule, Shufeng Jiedu capsule, or Jinfang Baidu pill, depending on the manifestations. For severe influenza, or mild influenza in patients at high risk of developing severe influenza, we suggest Lianhua Qingwen capsule in combination with antiviral medications and supportive therapy. The strength of all recommendations was weak. Traditional Chinese medicine has great potential to help in the fight against influenza worldwide, but more high-quality studies are still needed to strengthen the evidence.

Clinical practice guideline on treating influenza in adult patients with Chinese patent medicines.

Influenza is a major public health problem worldwide. Mutations and resistance development make the use of antiviral therapy challenging. Chinese patent medicines are often used to treat influenza in China and well tolerable. However, the misuse of Chinese patent medicines is common. We therefore aimed to develop an evidence-based guideline on treating influenza with Chinese patent medicines in adults to guide clinical practice. We formed a steering committee, a consensus panel, a consultants' group and an evidence synthesis team to guide the development of the guideline. We formulated the clinical questions through two rounds of survey, and finally selected five questions. We then systematically searched the related evidence and conducted meta-analyses, evidence summaries and GRADE decision tables to draft the recommendations, which the consensus panel then voted on using the Delphi method. Finally, we formulated six recommendations based on the evidence synthesis and experts' consensus. For treating mild influenza, we suggest either Lianhua Qingwen capsule, Jinhua Qinggan granule, Banlangen granule, Shufeng Jiedu capsule, or Jinfang Baidu pill, depending on the manifestations. For severe influenza, or mild influenza in patients at high risk of developing severe influenza, we suggest Lianhua Qingwen capsule in combination with antiviral medications and supportive therapy. The strength of all recommendations was weak. Traditional Chinese medicine has great potential to help in the fight against influenza worldwide, but more high-quality studies are still needed to strengthen the evidence.

Effect of Panax Ginseng (G115) Capsules versus Placebo on Acute Exacerbations in Patients with Moderate to Very Severe COPD: A Randomized Controlled Trial.

Purpose: Herbal medicines are commonly used by people with chronic obstructive pulmonary disease (COPD) but high quality randomized controlled trials are limited. This study evaluated the therapeutic value of ginseng capsules in reducing acute exacerbations and improving the quality of life in people with COPD. Patients and Methods: This randomized, double-blind and placebo-controlled trial assessed ginseng's effects on 200 patients with moderate to very severe COPD. Ginseng capsules (200 mg, twice per day) were compared to placebo over 24 weeks. Patients were followed up for a further 24 weeks after the treatment period. The primary outcome measure was acute COPD exacerbation rate over 12 months. Secondary outcome measures were health-related quality of life, including the St George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT) and the Short Form 36 Health Survey (SF-36). We also assessed lung function, walking distance and use of relief medication. Results: Baseline characteristics were balanced between groups. The rate of COPD exacerbations was not statistically significant between groups after 1 year (62 participants in the ginseng group and 63 in the placebo group). Secondary outcome measures showed improvements after ginseng and placebo but results were not clinically significant. The incidence of adverse events in the two groups was similar and events were unrelated to the intervention. Conclusion: Compared with placebo, ginseng did not reduce the rate of acute COPD exacerbations over 12 months. It was safe and well tolerated by people with moderate to very severe COPD.

Is Chinese Medicine Injection Applicable for Treating Acute Lung Injury and Acute Respiratory Distress Syndrome? A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To assess the efficacy and safety of Chinese medicine injection (CMI) for treating acute lung injury/acute respiratory distress syndrome (ALI/ARDS). METHODS: Randomized controlled trials (RCTs) were identified by searching 3 English databases and 4 Chinese databases from their inceptions until February 2019. The Cochrane Handbook was used to evaluate risk of bias in the included studies. Data analysis was conducted using RevMan 5.3.3 software. RESULTS: A total of 19 eligible RCTs involving 1,334 participants was included in this systematic review and meta-analysis. The main meta-analysis showed that CMI combined with conventional therapy (CT) was more effective than CT alone in reducing the acute physiology and chronic health evaluation (APACHE) H score [mean difference (MD): -1.74 points, 95% confidence interval (CI): -2.77 to -0.71, I2=0] and increasing the total effective rate [relative risk (RR): 1.35, 95% CI: 1.17 to 1.56, I2=37%]. Compared with CT, CMI combined with CT showed improvements in the arterial partial pressure of oxygen (PaO2, MD: 9.25 mm Hg, 95% CI: 0.87 to 17.63, I2=98%) and oxygenation index [arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2), MD: 50.75 mm Hg, 95% CI: 35.18 to 66.31, I2=94%]. CMI plus CT was superior to CT in reducing the systemic inflammatory response syndrome (SIRS) score (MD: -0.84 points, 95% CI: -1.26 to -0.42, I2=65%), length of hospital stay (MD: -4.22 days, 95% CI: -6.49 to -1.95, I2=92%), and duration of mechanical ventilation (MD: -2.94 days, 95% CI: -4.68 to -1.21, I2=89%). Only 1 study reported adverse events. CONCLUSIONS: CMI as an adjuvant therapy showed great potential benefits for the treatment of ALI/ARDS. However, we could not make a definite conclusion due to low quality of included studies and uncertain security. Future studies should focus on improving research design, especially in blindness and placebo. The reporting of adverse events was also needed.

Glutamine affects T24 bladder cancer cell proliferation by activating STAT3 through ROS and glutaminolysis.

Changes in metabolism are common phenomena in tumors. Glutamine (Gln) has been documented to play a critical role in tumor growth. In this study, we aimed to to explore the mechanisms through which bladder cancer cells utilize Gln to fulfill their biosynthetic needs during proliferation. In addition, the roles of Gln in the tricarboxylic acid (TCA) cycle, reactive oxygen species (ROS) regulation, and signal transducer and activator of transcription 3 (STAT3) expression were examined in vitro in the T24 bladder cancer cell line. The results revealed that the T24 cell line was markedly Gln­dependent and that Gln supplementation promoted T24 proliferation through the actions of Gln as a ROS moderator and as a metabolic fuel in the TCA cycle. Importantly, extracellular Gln deprivation deregulated the production of the transcription factor, STAT3. Additionally, STAT3 expression was affected by the degree of Gln metabolism, as regulated by Gln intermediates and ROS. Thus, on the whole, the findings of this study demonstrate that Gln promotes the proliferation of the Gln­dependent bladder cancer cell line, T24, by supplementing adenosine triphosphate (ATP) production and neutralizing ROS to activate the STAT3 pathway.

Effectiveness and Safety of Oral Cordyceps sinensis on Stable COPD of GOLD Stages 2-3: Systematic Review and Meta-Analysis.

Cordyceps sinensis (CS) is a complementary medicine used for Chronic Obstructive Pulmonary Disease (COPD) of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 2-3. Many randomized controlled trials have been conducted to evaluate the effect of CS alone or in combination with other herbs on stable COPD. To provide a synthesis of the evidence, we searched nine major electronic databases for randomized controlled trials on CS published before 21st December 2016. Fifteen interventional studies, including 1,238 participants, met the inclusion criteria. Meta-analysis showed that both CS preparations and CS formulae showed the potential benefits in lung function, exercise endurance, life quality, and improvement of symptoms. No serious adverse events were reported. So CS may be a promising treatment for patients with stable COPD of GOLD stages 2-3. No studies were placebo-controlled or of high methodological quality, which limits the conclusions.

12-month randomised controlled trial of ginseng extract for moderate COPD.

BACKGROUND: Panax ginseng (ginseng) is a therapeutic herb which might be beneficial in COPD. The study investigated if ginseng, compared with placebo, is effective and safe for people with moderate COPD. METHODS: This multicentre, randomised, double-blind, placebo-controlled trial compared 24 weeks of ginseng capsules (100 mg twice daily) with placebo. Participants were followed up for a further 24 weeks. Participants were aged 40 years and over and had airflow limitation in the moderate (Global Initiative for Chronic Obstructive Lung Disease 2) COPD range. The coprimary endpoints were the St George's Respiratory Questionnaire, the COPD Assessment Test and the Short Form Health Survey. Secondary outcomes included lung function, exacerbation rate and use of relief medication. FINDINGS: 168 participants were randomised 1:1 from five centres in Australia and China. Baseline characteristics were balanced between groups. There were no significant differences between ginseng and placebo, with overall results improving in both groups. Ginseng seemed safe for, and well tolerated by, people with COPD. INTERPRETATION: There was no significant difference in improvement in health-related quality of life (primary outcome) between the ginseng and placebo groups. TRIAL REGISTRATION NUMBER: ACTRN12610000768099.

Protective Effect of Jianpiyifei II Granule against Chronic Obstructive Pulmonary Disease via NF-κB Signaling Pathway.

Jianpiyifei II granule (JPYF II) is an oriental herbal formula used clinically in China to treat chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the anti-inflammatory and antioxidative activities of JPYF II in a mouse model of COPD induced by lipopolysaccharide (LPS) and cigarette smoke (CS) and in RAW264.7 cells stimulated with cigarette smoke extract (CSE). Mice were given LPS via intratracheal instillation on days 1 and 15 and exposed to CS generated from 4 cigarettes/day for 28 days. The mice were treated with 0.75, 1.5, or 3 g/kg/d JPYF II by intragastric administration in low, middle, and high dose groups, respectively, for two weeks. RAW264.7 cells were stimulated by CSE and treated with JPYF II at doses of 12.5, 25, or 50 µg/mL. In the mouse model of LPS and CS-induced COPD, JPYF II decreased inflammatory cell counts in broncho alveolar lavage fluid (BALF), in addition to mRNA expression of proinflammatory cytokines and metalloproteinases (MMPs) in lung tissues. In addition, JPYF II elevated catalase (CAT) and glutathione peroxidase (GSH-Px) activities and reduced the levels of malondialdehyde (MDA) and IκBα and p65 phosphorylation and inflammatory cell infiltration in the lung tissues. In RAW264.7 cells stimulated with CSE, JPYF II inhibited the mRNA levels of inflammatory mediators and the phosphorylation of IκBα and p65. Our results suggest that JPYF II enhanced anti-inflammatory and antioxidative activities in a mouse model of COPD induced by LPS and CS and in RAW264.7 cells stimulated with CSE via inhibition of the NF-κB pathway.

N-Acetyl-Glucosamine Sensitizes Non-Small Cell Lung Cancer Cells to TRAIL-Induced Apoptosis by Activating Death Receptor 5.

BACKGROUND/AIMS: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity. However, many human non-small cell lung cancer (NSCLC) cells are partially resistant to TRAIL, thereby limiting its clinical application. Therefore, there is a need for the development of novel adjuvant therapeutic agents to be used in combination with TRAIL. METHODS: In this study, the effect of N-acetyl-glucosamine (GlcNAc), a type of monosaccharide derived from chitosan, combined with TRAIL was evaluated in vitro and in vivo. Thirty NSCLC clinical samples were used to detect the expression of death receptor (DR) 4 and 5. After GlcNAc and TRAIL co-treatment, DR expression was determined by real-time PCR and western blotting. Cycloheximide was used to detect the protein half-life to further understand the correlation between GlcNAc and the metabolic rate of DR. Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to detect receptor clustering, and the localization of DR was visualized by immunofluorescence under a confocal microscope. Furthermore, a co-immunoprecipitation assay was performed to analyze the formation of death-inducing signaling complex (DISC). O-linked glycan expression levels were evaluated following DR5 overexpression and RNA interference mediated knockdown. RESULTS: We found that the clinical samples expressed higher levels of DR5 than DR4, and GlcNAc co-treatment improved the effect of TRAIL-induced apoptosis by activating DR5 accumulation and clustering, which in turn recruited the apoptosis-initiating protease caspase-8 to form DISC, and initiated apoptosis. Furthermore, GlcNAc promoted DR5 clustering by improving its O-glycosylation. CONCLUSION: These results uncovered the molecular mechanism by which GlcNAc sensitizes cancer cells to TRAIL-induced apoptosis, thereby highlighting a novel effective agent for TRAIL-mediated NSCLC-targeted therapy.

A systematic review and meta-analysis of the herbal formula Buzhong Yiqi Tang for stable chronic obstructive pulmonary disease.

OBJECTIVE: To systematically evaluate the efficacy and safety of Buzhong Yiqi Tang (BZYQT) for stable chronic obstructive pulmonary disease (COPD). METHODS: Three electronic English databases (PubMed, EMBASE and CENTRAL) and four Chinese databases (CBM, CNKI, CQVIP and WFMO) were searched from their inceptions until 30th June 2016. Participants were diagnosed with COPD according to the Chinese Medical Association's COPD diagnosis and treatment guidelines or Global Initiative for Chronic Obstructive Lung Disease (GOLD), and were in stable stage. Randomized controlled trials (RCTs) of oral BZYQT, alone or combined with conventional treatment, compared with conventional treatment alone or plus placebo were included in the review. Clinical improvement and the six-minute walking test (6MWT) were the primary outcome measures. The secondary outcome measures were defined as forced expiratory volume in one second (FEV1), forced vital capacity (FVC), respiratory muscle strength index with maximum inspiratory pressure (MIP), COPD Assessment Test (CAT), and frequency of acute exacerbations. To assess risk of bias the Cochrane, Risk of Bias tool was used, and statistical analysis was performed using RevMan 5.3.0 software. RESULTS: Sixteen studies (1400 participants) were included. The results of meta-analysis indicated patients receiving BZYQT alone or BZYQT in combination with conventional treatment showed a significant increase in clinical improvement (RR 1.25, 95% CI 1.18 to 1.33, I2=0%), enhanced exercise capacity 6MWT (MD 51.22m, 95% CI 45.56 to 56.89, I2=44%), improved lung function FVC (L) (MD 0.26 liters, 95% CI 0.18 to 0.33, I2=37%), reduced respiratory muscle fatigue MIP (MD 0.46 liters, 95% CI 0.11 to 0.80, I2=0%), and improved quality of life CAT (MD -2.56 points, 95% CI -3.40 to -1.72, I2=0%) when compared with conventional treatment alone, or plus placebo. BZYQT also showed small but significant improvements in FEV1% and decreased acute exacerbations of COPD. Four studies reported that no adverse events occurred, other studies did not mention adverse events. The finding should be considered with caution because the included studies had methodological shortfalls. CONCLUSIONS: BZYQT improves clinically important outcomes for patients with stable COPD, such as improved clinical symptoms, exercise capacity, lung function and quality of life. Moreover, it has an excellent safety profile. However further evaluation is needed to validate these preliminary findings in high quality RCTs.

Panax ginseng therapy for chronic obstructive pulmonary disease: a clinical trial protocol and pilot study.

BACKGROUND: Panax ginseng (Ren shen) has been used to treat chronic obstructive pulmonary disease (COPD). This article aims to present a study protocol and pilot trial comparing P. ginseng with placebo for treating moderate to very severe COPD. METHODS: COPD was diagnosed spirometrically, with participants having a forced expiratory volume in one second (FEV1) of between 20% and 79% and FEV1 to forced vital capacity (FVC) ratio of less than 70%. Outcome measures included exacerbation rate, St. Georges Respiratory Questionnaire, COPD Assessment Test and Short-form Health Survey (SF-36). Other outcome measures included the six-minute walk test, FEV1, FVC, relief medication use, use of COPD-specific medical resources, and adverse events. The study is a randomized, double-blind, placebo controlled clinical trial. The method of this pilot trial was based on a planned full-scale trial except that participants were enrolled for ten weeks compared to 52 weeks. In the pilot trial, 14 participants (57-73 years old) with moderate to very severe COPD were recruited from a community health program at a public Chinese medicine hospital in Guangdong Province, China. After a 2-week run-in period, 10 participants were eligible for the study and were randomly assigned to either P. ginseng group (n = 5) (200 mg twice daily for four weeks) or placebo group (n = 5), and then followed-up for an additional 4 weeks for a total of 10 weeks. RESULTS: Nine participants completed the trial and one dropped out. The exacerbation rate could not be evaluated because there were no exacerbations. One participant in P. ginseng group reported events of sore throat, cough and fever. Trial investigators did not consider these events as COPD exacerbations or adverse events. CONCLUSIONS: Participant recruitment, study design, data collection and outcome measurement have been tested in a pilot trial. A full-scale trial is warranted.