Exploration of biomarkers for efficacy evaluation of traditional Chinese medicine syndromes of acute exacerbation of chronic obstructive pulmonary disease based on metabolomics.

Background: Traditional Chinese medicine (TCM) is effective for the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD); however, there is no objective index for the evaluation of TCM syndrome efficacy. This study aimed to screen biomarkers related to the efficacy of TCM syndrome using metabolomics. Methods: We recruited AECOPD patients with phlegm-heat congesting lung (PH)/phlegm-damp amassing lung (PD) syndrome and treated them with Chinese herbal medicine (Qingre Huatan or Zaoshi Huatan granules) in addition to conventional medicine for 7 days. Data on clinical symptoms and sign scores, modified British Medical Research Council (mMRC), COPD assessment test (CAT), and inflammation indicators, including white blood cell (WBC) count, percentage of neutrophil count (NEU%), and C-reactive protein (CRP), were collected before and after treatment to evaluate the therapeutic effect. Serum samples were collected before and after treatment for metabolomic analysis to screen differential metabolites. Results: A total of 69 patients with AECOPD were enrolled, including 41 and 28 patients in the PH and PD groups, respectively. The clinical symptoms and sign scores, CAT, mMRC, NEU%, and CRP levels after treatment were lower than those before treatment in both groups (p < 0.05). Serum metabolomics analysis showed that there were 13 differential metabolites in the PH group and 16 differential metabolites in the PD group before and after treatment (p < 0.05, variable importance projection (VIP) ≥ 1.00). In the PH group, lysophosphatidylcholine (LPC) (16:0), LPC (17:1), LPC (18:3), LPC (18:2), and LPC (17:0) negatively correlated with clinical symptoms and sign scores (p < 0.05); LPC (16:0), LPC (17:1), LPC (16:1), and LPC (17:0) negatively correlated with WBC (p < 0.05) and NEU% (p < 0.05); and LPC (16:0) negatively correlated with CRP levels. In the PD group, L-phenylalanine positively correlated with CRP levels (p < 0.05), and 2-methylbutyroylcarnitine positively correlated with clinical symptoms and sign (p < 0.05) and CAT scores (p < 0.05). DL-carnitine positively correlated with clinical symptoms and sign scores (p < 0.05). Conclusion: Serum metabolites may be potential indicators to objectively evaluate the efficacy of TCM syndromes; however, further large controlled trials are required to verify these findings.

Efficacy and safety of traditional Chinese medicine in patients with acute exacerbation of idiopathic pulmonary fibrosis: study protocol for randomized, controlled, exploratory clinical trial.

BACKGROUND: At present, there is short of effective treatment for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). The treatment of IPF with traditional Chinese medicine (TCM) has some advantages. However, the evidence is unclear whether TCM can be recommended as an effective therapy to treat AE-IPF. The purpose of the study is to explore the efficacy and safety of TCM for patients with AE-IPF. METHODS: A randomized, double-blind, placebo-controlled, exploratory clinical trial will be performed. A total of 80 patients diagnosed with AE-IPF will be randomized into the intervention or control group. In addition to conventional treatment, the intervention group will be treated with Kangxianhuanji granule, and the control group will be given a placebo granule. The administration frequency is 10 g each time and two times daily. After 4 weeks of treatment, the patients were followed up for 12 weeks. The primary outcomes are treatment failure rate and all-cause mortality. Secondary outcome measures will include the length of hospitalization, overall survival, acute exacerbation rate, intubation rate, Modified British Medical Research Council (mMRC) score, the St George's Respiratory Questionnaire idiopathic pulmonary fibrosis (SGRQ-I) score, and arterial blood gas analysis. DISCUSSION: TCM may be beneficial in IPF. However, it has never been evaluated in patients with AE-IPF, who are incredibly prone to respiratory failure and have a high mortality rate. It is the first clinical trial to explore the efficacy and safety of TCM in the treatment of AE-IPF. This result will provide a basis for further study, which provides a high-quality evidence for the treatment of AE-IPF with TCM. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900026289 . Registered on 29 September 2019.

Effect of sequential treatment with TCM syndrome differentiation on acute exacerbation of chronic obstructive pulmonary disease and AECOPD risk window.

OBJECTIVE: To evaluate the efficacy and safety of the comprehensive interventions based on three Traditional Chinese medicine (TCM) patterns therapy in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and AECOPD risk window. METHODS: A prospective, multi-center, single-blinded, double-dummy and randomized controlled clinical trial is being conducted to test the therapeutic effects of a sequential two stage treatment. A total of 364 patients were enrolled into this study with 182 in each treatment group (TCM and conventional). Patients received medication (or control) according to their assigned group. TCM treatment according to syndrome differentiation for AECOPD were administered twice daily to patients with AECOPD over 7-21days, followed by TCM for AECOPD risk window (RW) over 28days. All patients were followed up for 6 months. Exacerbations were used as the primary outcome measures. Forced expiratory volume in the first second (FEV1) and the modified medical research council dyspnea (MMRC) scale, quality of life and mortality rate were used as secondary outcome measures. RESULTS: Of 364 randomized patients, 353 were included in the intention-to-treat analysis and 290 in the per-protocol analysis. In the TCM group, 16 patients (10.4%) reached the primary end point; 24 (17.7%) in the conventional group (RR 0.59, 95% CI 0.33-1.06; p=0.074). Among patients with a re-exacerbation, the median time to event was 107.5days (interquartile range [IQR], 39.5-129.0) in the TCM and 50days (IQR, 31-130.5) in the conventional group (P=0.011). After exacerbation therapy and a further 180-days follow-up, patients in the TCM group had significant improvements in dyspnea, as measured by MMRC (P=0.003), Patients in the TCM group also had improvements in health-related quality of life (P=0.002), as measured COPD Assessment Test (CAT). There was no difference between groups in death, and recovery of lung function. There were no differences between the TCM and conventional treatment group in adverse events. CONCLUSIONS: In patients presenting to the respiratory department with acute exacerbations of COPD, TCM treatments with syndrome differentiation will have beneficial effects with regard to re-exacerbation, relieving symptoms, improving quality of life for COPD patients.

Effectiveness and safety of traditional Chinese medicine on stable chronic obstructive pulmonary disease: A systematic review and meta-analysis.

OBJECTIVE: This study was intended to evaluate the efficacy and safety of Traditional Chinese Medicine (TCM) on stable chronic obstructive pulmonary disease (COPD). METHOD: A systematic review was conducted of clinical trials that compared TCM plus conventional medicine treatment versus conventional medicine treatment alone. Randomized controlled trials (RCTs) of clinical therapeutic studies on COPD by TCM were included. Searches were applied to the following electronic databases: The PubMed、 the Cochrane Library、CNKI、CBM and VIP. No blinding and language restriction was used. All trials included were analyzed according to the criteria of the Cochrane Handbook. Review Manager 5.2 software was used for data analysis. RESULT: 37 randomized clinical trials enrolling 3212 patients were included. Follow-up duration ranged from 4 weeks to 1.5 years. Compared to conventional medicine treatment alone, TCM plus conventional medicine treatment showed improvement in forced expiratory volume in one second (FEV1) (MD 0.12 L; 95% CI 0.08 to 0.16), and less exacerbation (OR -0.86; 95% CI -1.13 to -0.60). TCM treatment also led to a statistically improvement in SGRQ score compared to placebo (MD -4.36; 95% CI -7.12 to -1.59). There was statistically significant difference in six-minute walk distance (MD 36.66 meters, 95% CI 24.57 to 48.74) found with TCM compared to placebo. CONCLUSION: Among patients with stable COPD, TCM plus conventional medical treatment therapy might be associated with reduction risk of exacerbation, improvement of lung function, better quality of life and higher exercise capacity. The results were limited by the methodological flaws of the studies. High quality studies are needed to provide clear evidence for the future use of TCM.

Clinical Investigation on Distribution of Syndrome in AECOPD-RW / 世界科学技术-中医药现代化

This article was aimed to explain the distribution of syndrome and study the change of pathogenesis in patients of acute exacerbation of chronic obstructive pulmonary disease risk-window (AECOPD-RW) based on clini-cal investigation. The data of the traditional Chinese medicine (TCM) syndrome of patients diagnosed as AECOPD into AECOPD-RW were collected from 8 hospitals. The database was established. Data was analyzed with SPSS 13.0 software. The results showed that among 15 basic syndromes, the syndrome of lung-qi deficiency was with the high-est frequency, which was followed by the syndrome of kidney-qi deficiency and syndrome of phlegm-dampness. A-mong 14 combined syndromes, the syndrome of lung-kidney qi deficiency and the syndrome of phlegm-dampness ac-cumulated in the lung were with the highest frequency. The common syndromes of AECOPD-RW were the syndrome of lung-kidney qi deficiency combined with the syndrome of phlegm-dampness accumulated in the lung, the syn-drome of lung-kidney qi deficiency, the syndrome of lung-spleen qi deficiency combined with the syndrome of phlegm-dampness accumulated in the lung, the syndrome of lung-spleen qi deficiency, the syndrome of lung-kidney qi-yin deficiency combined with the syndrome of phlegm-dampness accumulated in the lung, the syndrome of lung-kidney qi-yin deficiency, the syndrome of lung-kidney qi deficiency combined with the syndrome of phlegm-stasis accumulated in the lung, and the syndrome of lung-kidney qi-yin deficiency combined with the syndrome of phlegm-stasis accumulated in the lung. It was concluded that the main common syndromes of AECOPD-RW was the mixture of deficiency and excess. There was relatively less pure deficiency and excess syndrome.

Therapeutic Effect Assessment Indexes of Randomized Controlled Trials on Traditional Chinese Medicine Syndrome Differentiation and Treatment of Chronic Obstructive Pulmonary Disease：A Systematic Review / 世界科学技术-中医药现代化

This study was aimed to review of the selection and use of the therapeutic effect assessment indexes of randomized controlled trials ( RCTs ) on traditional Chinese medicine ( TCM ) syndrome differentiation and treatment of chronic obstructive pulmonary disease ( COPD ) based on clinical efficacy . Published studies were searched in the CBM , CNKI , VIP , Wanfang database , Cochrane Library , PubMed and Embase to identity all RCTS on TCM treatment of COPD . Two researchers selected studies and extracted data independently using a designed extraction form . The Cochrane collaboration software RevMan 5 . 1 was used for meta-analysis . The re-sults showed that a total of 40 RCTs were included . Meta-analyses showed that TCM syndrome differentiation and treatment of COPD can improve the pulmonary function and life quality , improve the clinical effect and TCM syndrome effect , reduce the number of acute exacerbation of COPD and improve clinical symptoms . Some therapeutic effect assessment indexes , such as pulmonary function , life quality , clinical comprehensive effect , the number of acute exacerbation of COPD, clinical symptoms and signs, syndrome effect and the integral of syndrome were used more frequent . Other indexes such as 6-min walk distance , BODE Index and health eco-nomic evaluation were used less frequently . It was concluded that TCM syndrome differentiation and treatment of COPD had certain therapeutic efficacy. A large number of strictly-designed, multicenter, high-quality RCTs are required because of the low quality of the included studies. The selection of therapeutic effect assessment indexes is still not standardized . The therapeutic effect assessment indexes should be selected based on differ-ent purposes of clinical studies with the clinical characteristics of TCM .

Effect of sequential treatment with syndrome differentiation on acute exacerbation of chronic obstructive pulmonary disease and "AECOPD Risk-Window": study protocol for a randomized placebo-controlled trial.

BACKGROUND: Frequent chronic obstructive pulmonary disease (COPD) exacerbation is a major cause of hospital admission and mortality. It has been reported that Traditional Chinese Medicine (TCM) may relieve COPD symptoms and reduce the incidence of COPD exacerbations, thus improving life quality of COPD patients. The acute exacerbation of COPD risk-window (AECOPD-RW) is the period after an exacerbation and before the patient returns to baseline. In the AECOPD-RW, patients are usually at increased risk of a second exacerbation, which may lead to hospital admission and high mortality. It may be beneficial for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients to receive interventions during AECOPD-RW. During exacerbations the treatment principle is to eliminate exogenous pathogens, whereas the AECOPD-RW treatment principle focuses on enhancing body resistance. METHODS/DESIGN: A prospective, multi-center, single-blinded, double-dummy and randomized controlled clinical trial is being conducted to test the therapeutic effects of a sequential two stage treatment, which includes eliminating pathogen and strengthening vital qi with syndrome differentiation. A total of 364 patients will be enrolled in this study with 182 in each treatment group (TCM and control). Patients received medication (or control) according to their assigned group. TCM for AECOPD were administered twice daily to patients with AECOPD over 7 to 21 days, followed by TCM for AECOPD-RW over 28 days. All patients were followed for six months. The clinical symptoms, the modified medical research council dyspnea (MMRC) scale and exacerbations were used as the primary outcome measures. Pulmonary function, quality of life and mortality rate were used as secondary outcome measures. DISCUSSION: It is hypothesized that sequentially eliminating pathogens and strengthening vital qi treatments with syndrome differentiation will have beneficial effects on reducing the frequency and duration of acute exacerbation, relieving symptoms and improving quality of life for COPD patients. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov, ChiCTR-TRC-11001460.

Protective effect of quercetin on in vitro cardiomyocyte injury induced by hydrogen peroxide / 中国组织工程研究

BACKGROUND: Cerebral infarction is commonly associated with blood stasis syndrome. Abnormal alternation of blood rheology is generally manifested as increased blood viscosity and hematocrit (HCT). In isometric hemodilution, a certain amount of red blood cell (RBC) is shifted by bleeding and simultaneously, isometric diluter is supplemented to reduce whole blood viscosity.OBJECTIVE: To observe the improvement of astragalus injection, the Chinese herb for qi tonification and isometric hemodilution on blood rheology in blood stasis syndrome of cerebral infarction.DESIGN: Randomized controlled experiment and case-control analysis were designed.SETTING: Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology. PARTICIPANTS: In cerebral infarction group (infarction group), 64 inpatients of senile ischemic cerebral vascular disease were collected from Union Hospital Affiliated to Huazhong University of Science and Technology from March 2002 to March 2004. Al l of cases were aged over 60 years and were in conformity with the diagnostic criteria on blood stasis syndrome. According to random number table, routine treatment group (routine group) and the group of integrative therapy of Chinese and western medicine (experimental group) were divided, 32 cases in each one. 47 healthy people of similar age and diagnosed with routine physical examination were selected in normal control. METHODS: In routine group, cerebral infarction was treated with routine therapy, including extending capacity, reducing viscosity, resisting coagulation, blocking aggregation of platelet and dehydration and general symp tomatic supporting treatment. In experimental group, on basis of routine treatment, isometric hemodilution and astragalus injection, the Chinese herb for qi tonification were used. 10% of total blood amount (about 450-650 mL) was collected from vein, and colloid solution of same volume was injected intravenously. The treatment was applied once every 5 days, continuously for 3 times. Astragalus injection 50 mL mixed with physical saline 250 mL was intravenous dropped, once per day, continuously for 3 weeks. MAIN OUTCOME MEASURES: ① Comparison of indexes in bloodrheology before and after treatment in routine group and experimental group. ② Comparison of indexes in blood rheology between normal control and infarction group. RESULTS: According to intention management, 64 patients and 47 normal persons all entered result analysis. ① Comparison between infarction group and normal control: RVB, HCT and PFC (fibrinogen) were higher than normal control [(3.90±0.73), (3.40±0.28) mPa·s; (46.39±6.03) %,(42.61±2.91)%; (3.25±0.75), (3.08±0.46) g/L, P < 0.01, 0.05], MTIE (de formity index of RBC) was lower than normal control (0.958±0.006, 0.961 Shen H,Lu YD.Study on quantitative messurement of immunohistochemical ±0.004, P < 0.05). ② Comparison between routine group and experimental group: Difference in some indexes presented before the treatment. After treatment, RVB, HCT and PFC in experimental grou p were all lower than routine group [(3.90±0.52), (4.21±0.68) mPa·s; (43.80±3.29)%, (48.47±4.50)%; (3.31±0.60), (3.68±0.67) g/L, P < 0.01, 0.05]. CONCLUSION: Isometric hemodilution therapy and astragalus injection reduces blood viscosity, improves blood rheology and alleviates clinical svmptoms of blood stasis syndrome in senile cerebral infarction.