Serum metabolomics analysis of patients with chronic obstructive pulmonary disease and 'frequent exacerbator' phenotype.

Chronic obstructive pulmonary disease (COPD) exacerbations accelerate loss of lung function and increased mortality. The complex nature of COPD presents challenges in accurately predicting and understanding frequent exacerbations. The present study aimed to assess the metabolic characteristics of the frequent exacerbation of COPD (COPD­FE) phenotype, identify potential metabolic biomarkers associated with COPD­FE risk and evaluate the underlying pathogenic mechanisms. An internal cohort of 30 stable patients with COPD was recruited. A widely targeted metabolomics approach was used to detect and compare serum metabolite expression profiles between patients with COPD­FE and patients with non­frequent exacerbation of COPD (COPD­NE). Bioinformatics analysis was used for pathway enrichment analysis of the identified metabolites. Spearman's correlation analysis assessed the associations between metabolites and clinical indicators, while receiver operating characteristic (ROC) analysis evaluated the ability of metabolites to distinguish between two groups. An external cohort of 20 patients with COPD validated findings from the internal cohort. Out of the 484 detected metabolites, 25 exhibited significant differences between COPD­FE and COPD­NE. Metabolomic analysis revealed differences in lipid, energy, amino acid and immunity pathways. Spearman's correlation analysis demonstrated associations between metabolites and clinical indicators of acute exacerbation risk. ROC analysis demonstrated that the area under the curve (AUC) values for D­fructose 1,6­bisphosphate (AUC=0.871), arginine (AUC=0.836), L­2­hydroxyglutarate (L­2HG; AUC=0.849), diacylglycerol (DG) (16:0/20:5) (AUC=0.827), DG (16:0/20:4) (AUC=0.818) and carnitine­C18:2 (AUC=0.804) were >0.8, highlighting their discriminative capacity between the two groups. External validation results demonstrated that DG (16:0/20:5), DG (16:0/20:4), carnitine­C18:2 and L­2HG were significantly different between patients with COPD­FE and those with COPD­NE. In conclusion, the present study offers insights into early identification, mechanistic understanding and personalized management of the COPD­FE phenotype.

Correlation of Coagulation Dysfunction with Infection and Hypercapnia in Acute Exacerbation of COPD Patients.

Background: This study aims to explore the factors influencing the coagulation function of patients with chronic obstructive pulmonary disease (COPD) and its effects on thrombosis. Methods: A total of 155 COPD patients, including 118 patients with acute exacerbation of COPD (AECOPD) and 37 patients with stable COPD (SCOPD), were enrolled in this study. Meanwhile, 50 patients with gastrointestinal polyps found during physical examination and treated with surgery in the same period were enrolled as the control group. The basic data, routine blood tests, C-reactive protein (CRP), procalcitonin (PCT), and coagulation indexes of the three groups were collected, as well as arterial blood gas indexes of AECOPD patients. Results: The differences in erythrocyte count and hemoglobin among groups were not statistically significant. Compared with the SCOPD group and control group, white blood cell (WBC), neutrophil percentage, PCT, CRP, prothrombin time (PT), and fibrinogen (FIB) in the AECOPD group increased significantly, while the international normalized ratio (INR) decreased (P < 0.05). The differences in activated partial thromboplastin time (APTT) and D-dimer among groups were not statistically significant (P > 0.05). Thrombin time (TT) in the AECOPD group was shorter than that of the control group, and PT was longer than that of the SCOPD group (P < 0.05). Five patients with AECOPD and one patient with SCOPD had venous thrombosis. Conclusion: The abnormal coagulation function in AECOPD patients is related to the degree of infection and hypercapnia, which may be a risk factor for thrombosis.

[Comparative study on serum transitional components of Huatan Jiangqi Capsules in rats under pathological and physiological status].

The differences of transitional components and metabolic processes of Huatan Jiangqi Capsules(HTJQ) in rats under normal physiological and pathological conditions of COPD were analyzed by UPLC-Q-TOF-MS. The rat COPD model was established by passive smoking and intratracheal instillation of lipopolysaccharide. After the normal and COPD model rats were douched with HTJQ, the blood was collected from hepatic portal vein and the drug-containing serum samples were prepared by methanol precipitation of protein. Then, 10 batches of drug-containing serum samples of HTJQ were prepared and analyzed by UPLC serum fingerprint to evaluate the quality and stability of drug-containing serum samples. UPLC-Q-TOF-MS was used to collect the mass spectrometric information of the transitional components. Twenty-eight transitional components of HTJQ in normal rats and 25 transitional components of HTJQ in COPD model rats were identified by UPLC-Q-TOF-MS. Under pathological and physiological conditions, there were not only the same transitional components in rat serum, but also corresponding differences. Further studies showed that there were also differences in the metabolic process of transitional components between the two conditions. In normal rats, most of the metabolic types of transitional components were phase I reactions. In COPD model rats, phase Ⅰ reactions decreased and phase Ⅱ reactions increased correspondingly. With UPLC-Q-TOF-MS technology, the differences of transitional components and the metabolism process of HTJQ in rats under normal physiological and pathological conditions were analyzed. The results showed that types of transitional components and the activity of some metabolic enzymes would be changed in COPD pathological state, which would affect the metabolic process of bioactive components in vivo. It laid a foundation for further elucidating the metabolic process and pharmacodynamic substance basis of HTJQ.

Allyl isothiocyanate upregulates MRP1 expression through Notch1 signaling in human bronchial epithelial cells.

Multidrug resistance associated protein-1 (MRP1) and Notch signaling are closely related and both play a critical role in chronic obstructive pulmonary disease (COPD) establishment and progression. The aim of our work was to test whether Notch1 is involved in allyl isothiocyanate (AITC) induced MRP1 expression. We used cigarette smoke extract (CSE) to simulate the smoking microenvironment in vitro. The results demonstrated that CSE led to apoptosis as well as reduced the expression of Notch1, Hes1, and MRP1, while AITC significantly reversed this downregulation. Transfected with Notch1 siRNA downregulated MRP1 expression and activity, aggravated the suppression effect by CSE, and abolished the AITC-induced Notch1, Hes1, and MRP1 expression. Validation of the correlation between Notch1 and MRP1 was implemented by gel-shift assays (electrophoretic mobility shift assay). The result revealed an interaction between a specific promoter region of MRP1 and the intracellular domain of Notch1. In conclusion, Notch1 signaling positively regulated MRP1 in 16HBE cells and AITC induced MRP1 expression and function may be attributed to Notch1 signaling. These findings show that Notch1 and MRP1 might have a potential protective effect in the COPD process and become a new therapeutic target for COPD or other lung diseases. It also provides a theoretical basis for the therapeutic effects of AITC.

Effect of Liuweibuqi capsules on CD4+CD25+Foxp3+ regulatory T cells, helper T cells and lung function in patients with stable chronic obstructive pulmonary disease complicated with lung Qi deficiency.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is predicted to become the fifth leading cause of disability and the third leading cause of death around the world by 2020. Though it is potentially treatable and preventable, evidence of brain structural alterations in COPD remains sparse and conflicting. We aim to investigate the effect of Liuweibuqi capsules on CD4+CD25+ Forkhead box protein 3+ (Foxp3+) regulatory T cells (Tregs), helper T cells (Th) and lung function in patients with stable COPD complicated with lung Qi deficiency. METHODS: COPD patients with lung Qi deficiency [458] were assigned into non-smoking COPD (NS-COPD), non-smoking control (NS-control), smoking COPD (S-COPD) and smoking control (S-control) groups, and healthy volunteers [245] into the non-smoking healthy (NSH) and smoking healthy (SH) groups. Levels of inflammatory cytokines were detected by Enzyme-linked immunoassay (ELISA). Contents of inflammatory cells, inflammatory marker, and CD4+CD25+Fox3+Tregs were measured by flow cytometry. FEV1/FVC (%) and FEV1 (%) were detected by pulmonary function test apparatus. Correlation between FEV1 (%) and Th1, Th2, Th17, Th1/Th2 or CD4+CD25+Fox3+Tregs was analyzed by Spearman rank correlation test. The related factors affecting treatment efficacy was assessed by logistic analysis. RESULTS: COPD patients and smoking people showed higher level of INF-γ, IL-4, IL-17, Th1, Th2, Th17 and Th1/Th2 but lower level of CD4+CD25+Fox3+Tregs. Liuweibuqi capsules could decrease level of inflammatory cells, cytokines, and markers (especially Th17 and IL-17), and increase level of CD4+CD25+Fox3+Tregs. FEV1 (%) negatively correlated with Th1, Th2, Th17 and Th1/Th2 but positively correlated with CD4+CD25+Fox3+Tregs, and smoking may strengthen their correlation, but Liuweibuqi capsules may weaker their correlation. Levels of inflammatory cytokines, cells, marker, CD4+CD25+Fox3+Tregs, FEV1/FVC (%), FEV1 (%), smoking and Liuweibuqi capsules are factors affecting efficacy. CONCLUSIONS: Taken together, our data support the notion that smoking is an important factor to induce and aggravate COPD. Liuweibuqi capsules could stimulate proliferation of CD4+CD25+Fox3+Tregs and decrease Th17 expression to improve the lung function in stable COPD patients with lung Qi deficiency, and it had obvious efficacy for smoking COPD patients.

Qiyusanlong decoction suppresses lung cancer in mice via Wnt/ß-catenin pathway.

Lung cancer is one of the most fatal cancers due to its high metastatic rate. Traditional Chinese medicine has been used in cancer patients for decades to improve quality of life and prolong survival time. The present study used a novel Qiyusanlong (QYSL) decoction composed of 10 kinds of Chinese medicine including astragalus membranaceus (Huangqi), polygonatumod oratum (yuzu), scolopendra (tianlong), pberetima (dilong), solanum nigrum (longkui), herbahedyotis (baihushecao), semen coicis (yiyiren), euphorbia helioscopia (zeqi), curcuma longa (eshu) and tendril-leaved fritillary bulb (chuanbei). The effects and function of the QYSL decoction remain to be elucidated. The present study established a mouse xenograft model using Lewis lung carcinoma cell injection and administered different doses of QYSL decoction to the mice. It was demonstrated that the chemotherapy drug Cisplatin (DDP) and QYSL decoction repressed lung tumor growth, and the inhibitory effect of DDP was more significant. Furthermore, QYSL decoction and DDP modulated the expression of regulatory proteins in the Wnt/ß­catenin pathway, including Wnt1, Wnt2, Wnt5a and glycogen synthase kinase 3ß, detected by western blotting, and affected the signals of cluster of differentiation 44 variation 6 and Survivin in tumor tissues, examined via immunohistochemistry. The combination of QYSL decoction and DDP enhanced the inhibitory effect. These data demonstrated that the QYSL decoction repressed lung tumor development via the Wnt/ß­catenin pathway. The therapeutic effect of QYSL decoction alone was milder compared with DDP, however the combination of QYSL decoction and chemotherapy exhibited an increased the rapeutic effect compared with the treatments administered alone. These findings revealed the function of QYSL decoction as a lung cancer treatment and provided insight for a novel lung cancer therapy.

Comparative analysis of immune function, hemorheological alterations and prognosis in colorectal cancer patients with different traditional Chinese medicine syndromes.

OBJECTIVE: The present study investigates the differences in immune function, hemorheological alterations and prognostic evaluation in colorectal cancer (CRC) patients with different traditional Chinese medicine (TCM) syndromes. METHODS: A total of 128 patients, diagnosed as stage II and III of CRC, were recruited. They were assigned into three TCM syndromes: deficiency syndrome, excess syndrome, and syndrome of intermingled deficiency and excess, and another 53 healthy individuals were selected as the control. Flow cytometry was used to determine the peripheral blood lymphocyte subsets (the levels of CD+3, CD+4, CD+8, NK cells, and the ratios of CD+4/CD+8, Th1/Th2 and Tc1/Tc2). Whole blood viscosity (WBV), plasma viscosity (PV), hematocrit (Hct), erythrocyte sedimentation rate (ESR), plasma fibrinogen concentration (PFC) were measured using a fully-automatic blood rheological instrument. The univariate analysis and Cox regression analysis were conducted to evaluate the prognosis of CRC patients with different TCM syndromes. RESULTS: Compared with healthy individuals, CRC patients with three different syndromes had lower levels of CD+3, CD+4, NK cells, and ratios of CD+4/CD+8, Th1/Th2 and Tc1/Tc2, but higher level of CD+8, WBV, PV, Hct, ESR and PFC. Besides, patients with excess syndrome showed the highest levels of CD3+, CD4+ and NK cells, and ratios of CD+4/CD+8, Th1/Th2 and Tc1/Tc2, but the lowest level of CD+8 among three syndromes, and those with deficiency syndrome showed an opposite trend. Compared with patients with excess syndrome, those with deficiency syndrome showed decreased WBV, PV, Hct, ESR and PFC. The pathological type, surgical approach, tumor node metastasis (TNM) stage, liver metastasis, TCM treatment time and different TCM syndromes were independent factors of prognostic survival in CRC patients except perioperative blood transfusion volume. CONCLUSIONS: Taken together, we conclude that patients with TCM deficiency syndrome has lower immune function and poorer prognosis while patients with TCM excess syndrome has higher immune function and better prognosis of CRC.

[Effect of Qibai Pingfei capsule medicated serum on protein expressions of KATP channel in pulmonary arterial smooth muscle cells via nitric oxide].

To investigate the ATP-sensitive potassium channel (KATP channel) protein expressions during different periods under hypoxia condition and explore the effect of Qibai Pingfei capsule medicated serum (hereinafter referred to as QBPF) on the correlation between the protein expressions of KATP channel and nitric oxide in rat pulmonary arterial smooth muscle cells(PASMCs). Qibai Pingfei capsules were given to SD rats via continuous gavage for 10 days to obtain QBPF. Primary rats PASMCs were cultured by the direct adherent culture method. Western blot was applied to detect the protein expression levels of KATP channel (Kir6.1 and SUR2B) in PASMCs. Then the noncompetitive inhibitor of NO synthase--Nω-nitro-L-arginine methyl ester(L-NAME) and KATP channel inhibitor--glyburide(GLYB) were applied respectively to evaluate the effect of QBPF on the protein expressions of KATP channel. The protein expressions of Kir6.1 and SUR2B were increased after 6-hour hypoxia treament, peaked at the 24-hour hypoxia treament, and decreased in both 48-hour and 72-hour hypoxia groups. Especially, QBPF could further up-regulate the Kir6.1 and SUR2B protein expressions under 24-hour hypoxia condition; however, such up-regulation effect could be blocked by KATP channel inhibitor GLYB and NO specific inhibitor L-NAME, indicating that QBPF played the role of opening KATP channel. The regulatory mechanism was probably associated with up-regulating KATP channel protein expression via NO relative pathway, involving pulmonary vasodilation, and thus relieving the occurence and development of COPD.

Allyl isothiocyanate increases MRP1 function and expression in a human bronchial epithelial cell line.

Multidrug resistance-associated protein 1 (MRP1), a member of the ATP-binding cassette (ABC) superfamily of transporters, plays an important role in normal lung physiology by protecting cells against oxidative stress and toxic xenobiotics. The present study investigates the effects of allyl isothiocyanate (AITC) on MRP1 mRNA and MRP1 protein expression and transporter activity in the immortalised human bronchial epithelial cell line 16HBE14o-. MRP1 mRNA and MRP1 protein expression in 16HBE14o- cells that were treated with allyl isothiocyanate were analysed by real-time PCR assay and Western blotting. The transport of carboxyfluorescein, a known MRP1 substrate, was measured by functional flow cytometry to evaluate MRP1 activity. Treatment with AITC at concentrations of 5-40 µM increased MRP1 protein levels in a concentration-dependent manner. AITC treatments at concentrations of 1-40 µM caused concentration-dependent increases in MRP1 mRNA levels that were up to seven times greater than the levels found in control cells. Finally, AITC treatment at concentrations of 5-40 µM significantly increased MRP1-dependent efflux in 16HBE14o- cells. These results suggest that AITC can increase the expression and activity of MRP1 in 16HBE14o- cells in a concentration-dependent manner. The upregulation of MRP1 activity and expression by AITC could produce therapeutic effects in the treatment of lung disease.

[Regulation of Thl/Th2 cells by T cell-mediated transcription factor in rats with chronic obstructive pulmonary disease].

OBJECTIVE: To determine T box expressed in T cells (T bet), GATA binding protein-3 (GATA 3), and retinoid-related orphan nuclear receptor gammat (RORgammat) in rats with chronic obstructive pulmonary disease (COPD). METHODS: Thirty rats were randomly divided into a control and a COPD group. The COPD model was established through smoking and lipopolysaccharide (LPS) tracheal instillation. Pulmonary function of the rats was measured 28 d after the establishment of the COPD model by a spirometer. Enzyme linked immunosorbent assay was performed to detect serum γ interferon (IFN-γ), interleukin (IL)-4, and IL-17. The expressions of T-bet, GATA-3, and RORgammat protein in lung tissues were determined by Western blot. RESULTS: Compared with the controls, the COPD rats had decreased pulmonary function and expression of serum IL-4, and increased INF-γ, IL- 17, Th1/Th2, T-bet, T bet /GATA-3, and RORgammat protein (P<0. 05). Forced expiratory volume in 0. 3 seconds (FEV 0.3) was negatively correlated with INF γ and T-bet/GATA-3. Forced vital capacity (FVC) was positively correlated with IL 4. FEV0.3/FVC was negatively correlated with Thl/Th2, T-bet and T-bet/GATA-3. Peak expiratory flow (PEF) was negatively correlated with IL-17, T bet, and RORgammat (P<0. 05). Thl/Th2 was positively correlated with T bet/GATA-3. IL-17 was positively correlated with RORgammat. T bet/GATA-3 was positively correlated with RORgammat (P<0. 05). CONCLUSION: Imbalanced regulation of T bet / GATA 3 and RORgammat on Th1/Th2 and Th17 cells is associated with the occurrence of COPD.

[Changes of CD4 + CD25 + Foxp3 + Regulatory T Cells in Different Stages of COPD and Intervention of Qibai Pingfei Capsules].

OBJECTIVE: To observe the changes in proportion of CD4 + CD25 + Foxp3 + regulatory T cells (Treg) in peripheral blood of different stages of CPOD and intervention of Qibai Pingfei Capsules. METHODS: The rats were randomly divided into three groups,including normal group, COPD group and Qibai Pingfei Capsules(2. 88 g/kg)group. At the end of 7,14,21 and 28 days,eight rats were sacrificed in each group. CD4 + CD25 + Foxp3 + Treg cells in peripheral blood were measured by flow cytometry method. RESULTS: Compared with normal group, the percentages of CD4 + % in peripheral blood were not significantly different at the end of 7, 14, 21 and 28 days. However, CD4 + CD25 + % and CD4 + CD25 + Foxp3 +/CD4 + were significantly increased and CD4 + CD25 + Foxp3 + Treg% were significantly decreased at the end of 14,21 and 28 days. Compared with model group, CD4 + CD25 + %, CD4 + CD25 + Foxp3 +/CD4 + were significantly decreased, CD4 + CD25 + Foxp3 + Treg % were significantly increased at different stages of CODP. CONCLUSION: Immune disorders may exist in COPD, and Treg cells may be involved in the process of COPD. Meanwhile,the protective effect in COPD rats of Qibai Pingfei Capsules may be associated with improving the percentage of suppressive CD4 + CD25 + Foxp3 + Tregs.

Effectiveness of Bufei Yishen Granule combined with acupoint sticking therapy on quality of life in patients with stable chronic obstructive pulmonary disease.

OBJECTIVE: To evaluate the efficacy of Bufei Yishen Granule BFYSG) combined with Shufei Tie acupoint sticking therapy on quality of life of patients with stable chronic obstructive pulmonary disease (COPD). METHODS: A multi-center, double-blinded, double-dummy and randomized controlled method was adopted in this trial. A total of 244 patients were randomly assigned to a trial group and a control group according to the random number, each with 122 patients; treatment allocation occurred when the participants met the inclusion criteria and signed the informed consent form. In the trial group, patients were treated with BFYSG combined with "Shufei Tie" acupoint sticking therapy and sustained-release theophylline dummy, and in the control group patients were treated with oral sustained-release theophylline and BFYSG dummy combined with "Shufei Tie" acupoint sticking therapy dummy. The therapeutic course for two groups was 4 months and the follow-up was 6 months. The frequency and duration of acute exacerbation calculated by adding up each frequency and duration of acute exacerbation in treatment and follow-up time respectively, the quality of life measured by the World Health Organization Quality of Life (WHOQOL)-BREF scale and adult COPD quality of life (COPD-QOL) scale were observed. RESULTS: Among the 244 enrolled patients, 234 were screened for full analysis set (FAS); 221 were screened for per-protocol analysis set (PPS). After 4-month treatment and 6-month follow-up there were differences between the trial group and the control group in frequency of acute exacerbation (FAS: P=0.013; PPS: P=0.046); duration of acute exacerbation (FAS: P=0.005; PPS: P=0.006); scores of physiological, psychological and environment aspects of the WHOQOL-BREF questionnaire (FAS: P=0.002, P=0.006, P=0.000; PPS: P=0.00, P=0.001, P=0.000); scores of daily living ability, social activity, depression symptoms aspects of the COPD-QOL questionnaire (FAS: P=0.000, P=0.000, P=0.006; PPS: P=0.002, P=0.001, P=0.001). CONCLUSION: BFYSG combined with acupoint sticking therapy could improve the quality of life of patients with stable COPD.

Functional mechanism of pingchuanning decoction on adjustment of Clara cell secretory protein in airway remodeling of asthmatic rats.

OBJECTIVE: To study the functional mechanism of pingchuanning decoction in treatment of airway remodeling in asthmatic rats. METHODS: Eighty healthy Wistar male rats were randomized into eight groups (n=10 rats each): Normal group, asthma model group, dexamethasone group, guilong kechuanning group, xiaoqinglong decoction group, and pingchuanning decoction low-, middle-, and high-dose groups. The rats of all but the normal group were made into asthma models through intraperitoneal injection and aerosol inhalation of ovalbumin. All treatments were administered at the first stimulation of asthma onset (third week of modeling), and the rats were killed after stimulating asthma attacks for 4 weeks. The general conditions of rats and pathomorphological changes of the lung tissues were observed. The expression of nerve growth factor (NGF) of the lung tissues was measured with immunohistochemical methods, and the content of clara cell secretory protein (CCSP) mRNA was determined with RT-PCR. RESULTS: Compared with the normal group, the contents of NGF and CCSP mRNA in the lung tissues of the model group were significantly changed (P < 0.01). Compared with the model group, the indices of pingchuanning decoction and other treatment groups were improved to some extent (P < 0.05 or P < 0.01). CONCLUSIONS: Pathological changes of airway inflammation and remodeling were present in these rat asthma models. Pingchuanning decoction had an intervention effect on these experimental models. Its functional mechanism may be related to multiple factors, including alleviation of airway inflammation, relief of bronchial smooth muscle spasm, and inhibition of airway remodeling.

Bu-Fei Yi-Shen granule combined with acupoint sticking therapy in patients with stable chronic obstructive pulmonary disease: a randomized, double-blind, double-dummy, active-controlled, 4-center study.

ETHNOPHARMACOLOGICAL RELEVANCE: Bu-Fei Yi-Shen granule combined with acupoint sticking therapy has been used in the patients with stable chronic obstructive pulmonary disease (COPD) as major traditional interventions for the treatment of the disease. AIM OF THE STUDY: The objective of this study was to evaluate the efficacy and safety of traditional Chinese herbal medicine, the Bu-Fei Yi-Shen granule combined with acupoint sticking therapy in patients with stable COPD. METHODS: A 4-center, double-blinded, double-dummy and randomized controlled method was conducted. 244 patients who were divided into the trial group (n=122, treated with Bu-Fei Yi-Shen granule combined with Shu-Fei Tie acupoint sticking therapy and oral placebo sustained-release theophylline) and the control group (n=122, treated with oral sustained-release theophylline and placebo Bu-Fei Yi-Shen granule combined with placebo Shu-Fei Tie acupoint sticking therapy). The frequency and duration of acute exacerbation, lung function, clinical symptoms, six-minute walking distance, dyspnea grade and quality of life were observed during the 4-month treatment period, and for a further 6 months follow-up. RESULTS: Two hundred and twenty one patients fully completed the study, intent-to-treat (ITT) population was 234 and per-protocol (PP) population was 221. After treatment for 4 months and follow-up for 6 months, there were differences between the experimental and control group in frequency of acute exacerbation (ITT: P=0.007, P=0.013; PP: P=0.045, P=0.046); duration of acute exacerbation (ITT: P=0.030, P=0.005; PP: P=0.048, P=0.006); scores of symptoms (ITT: P=0.000, P=0.000; PP: P=0.000, P=0.000); six-minute walking distance (ITT: P=0.002, P=0.001; PP: P=0.002, P=0.001); dyspnea grade (ITT: P=0.014, P=0.009; PP: P=0.018, P=0.012); physiological aspects (ITT: P=0.003, P=0.000; PP: P=0.001, P=0.000); psychological aspects (ITT: P=0.007, P=0.001; PP: P=0.001, P=0.000) and environment aspects (ITT: P=0.003, P=0.000; PP: P=0.001, P=0.000) of the WHOQOL-BREF questionnaire. There were no differences between the experimental and control group in FVC, FEV1 and FEV1% and adverse events. CONCLUSIONS: Bu-Fei Yi-Shen granule combined with acupoint sticking therapy showed beneficial effects for patients with stable COPD in the measured parameters over the 4-month treatment period and 6 months follow-up, with no relevant between-group differences in adverse events.

[Plasma metabonomic studies on the stable phase chronic obstructive pulmonary disease patients of Fei-qi deficiency syndrome and the Chinese materia medica intervention].

OBJECTIVE: By using the metabonomics method, to study the plasma metabonomics of the stable phase chronic obstructive pulmonary disease (COPD) patients of Fei-qi deficiency syndrome (FQDS), and of Chinese materia medica (CMM) intervention, thus exploring possibly existent biomarkers. METHODS: Forty stable phase COPD patients of FQDS were recruited as Group A. Liuwei Buqi Capsule (LWBQC) was given to them as intervention. A healthy control group (Group B, 37 cases) was set up. The pulmonary function test was performed on patients in Group B and Group A before and after intervention. The plasma metabolites were detected using high performance liquid chromatography-mass spectrometry (HPLC-MS/MS). Statistical data were analyzed using principal component analysis (PCA) and partial least squares (PLS). The original spectrum and data of plasma metabonomics were compared between the two groups. The whole spectrum amino acid metabonomics tests were performed in the two groups. RESULTS: Compared with Group B, the pulmonary function significantly decreased before intervention in Group A (P < 0.05). The pulmonary function was more mildly improved after 30 days' treatment than before treatment, but still lower than it in Group B (P < 0.05). The metabolic spectrum before treatment in Group A was significantly different from Group B, but showing regressive trend to Group B after treatment. Fifteen possible disease markers were found in COPD patients of FQDS. Results of the whole spectrum of amino acid metabolomics showed different features. CONCLUSIONS: The changes of metabolic spectrum and amino acids could be found in the stable phase COPD patients of FQDS using plasma metabonomics, and potential markers could be detected. The intervention of the stable phase COPD patients of FQDS by Chinese medicine could brought positive changes in the metabolic profiling and amino acid metabolism.

[Preliminary study on differential expressed genes in T lymphocyte of chronic obstructive pulmonary disease patients with Fei-qi deficiency syndrome].

OBJECTIVE: To study T lymphocyte related genes with differential expression in patients with chronic obstructive pulmonary disease (COPD) of Fei-qi deficiency (FQD) syndrome type by gene chips. METHODS: Lymphocytes in peripheral blood were isolated by Ficoll technique from blood samples collected from COPD patients of FQD syndrome type, Fei-yin deficiency (FYD) syndrome type, and also from healthy subjects for control. They were sorted and purified by flow cytometry, and the different expressed genes were screened from them by gene chip technique. RESULTS: There were 15 genes with high differential expression between patients of FQD type and those of FYD syndrome type, and between patients of FQD type and healthy subjects. CONCLUSION: Gene chip technique could be used for studying the gene expression profiles of TCM syndrome, and the T-lymphocyte related genes with differential expression in COPD patients with FQD were screened preliminarily.

[Study on establishment of Alzheimer's disease animal model and intervening effect of zhinao capsule on it].

OBJECTIVE: To establish an experimental animal model of Alzheimer's disease (AD) with clinical and pathological specificity conformed to AD in human, and to observe the effect of Zhinao Capsule (ZNC) on learning, memory and patho-morphological parameters in the model. METHODS: The experimental AD model of rats was improved and established by combined injection of beta-amyloid protein (beta-AP) to lateral ventricle and transforming growth factor beta 1 (TGF beta 1) to brain. The learning and memory function of the model rats were tested by step-through test and water-maze test, and the number and cross area of beta-AP deposited macula in cerebral cortex and CA1 region of hippocampus were estimated quantitatively using immunohistochemical method and image pattern analysis. RESULTS: The improved AD animal model showed both the specificity of behavior (learning and memory impairments) and the typical pathological specificity (beta-AP deposited macula). ZNC could effectively improve the impairment of learning and memory and reduce the number and cross area of beta-AP deposited macula in cerebral cortex and hippocampus CA1 region in the AD model rats. CONCLUSION: The AD rat model induced by the combined injection of beta-AP and TGF beta 1 is a good animal model simulated to the clinical reality, which could be used to screen and evaluate the anti-dementia agents. ZNC could display anti-dementia effect of the AD model rats.