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.

Distribution characteristics of traditional Chinese medicine syndromes in 4 367 adult influenza patients: a Meta-analysis / 中华危重病急救医学

Objective:To systematically evaluate the distribution characteristics of traditional Chinese medicine (TCM) syndromes in adult influenza patients and to provide a basis for the TCM syndrome differentiation of influenza.Methods:The CNKI, CBM, Wanfang, VIP, PubMed, Embase, Cochrane Library databases were searched to collect cross -sectional studies on the distribution pattern of TCM syndromes in adult patients with influenza. The risk of bias assessment tool for cross -sectional studies developed by the Joanna Briggs Institute (JBI) evidence -based health care center was used to evaluate the literature quality, and the Stata 15.1 software was used to conduct a Meta -analysis of the pooled effect sizes of the included studies. Results:A total of 11 studies with 4 367 influenza patients were included. Quality assessment results of JBI showed that the risk bias was higher in the sample size calculation, and the description of sampling modalities and response rate was unclear. There were 17 influenza syndromes after specification, and a single group rate Meta -analysis was performed of the syndromes with ≥ 50 incident cases showed that there were 9 syndromes with an incidence ≥ 10% and statistical significance, the top 5 syndromes were syndrome of wind and heat invading the defense [ n = 1 583, RATE = 34.3%, 95% confidence interval (95% CI) was 22.2%-46.3%], syndrome of exterior cold and interior heat ( n = 1 122, RATE = 36.1%, 95% CI was 21.2%-51.1%), syndrome of wind -cold fettering the exterior ( n = 860, RATE = 19.4%, 95% CI was 10.7%-28.0%), syndrome of heat and toxin in the lung ( n = 217, RATE = 17.1%, 95% CI was 9.1%-25.0%), and syndrome of disease involving both defense phase and qi phase ( n = 184, RATE = 38.8%, 95% CI was 14.2%-63.5%). The results of the subgroup analysis in different geographical regions showed that the frequency of distribution of syndrome of wind and heat invading the defense and heat and toxin in the lung was higher in the South (RATE: 36.5%, 18.6%) than in the North (RATE: 30.9%, 15.4%), and the frequency of distribution of syndrome of wind -cold fettering the exterior and exterior cold and interior heat in the North (RATE: 23.8%, 40.1%) was higher than that in the South (RATE: 15.7%, 32.3%). Conclusions:There are 9 common TCM syndromes of influenza, including wind and heat invading the defense syndrome, exterior cold and interior heat syndrome, wind -cold fettering the exterior syndrome, heat and toxin in the lung syndrome, disease involving both defense phase and qi phase syndrome, wind and heat complicated by dampnessinvading the surface syndrome, wind and cold complicated by dampnessinvading the surface syndrome, defense phase syndrome and dampness and heatinvading the surface syndrome, which can provide a reference for the TCM syndrome differentiation and treatment of influenza.

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.

Interaction Between Intestinal Flora and Chronic Renal Failure and Traditional Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

Chronic renal failure （CRF）， a common outcome of various chronic kidney diseases， is characterized by retention of metabolites and toxins， water-electrolyte imbalance， acid-base disturbance， and various symptoms in diverse systems. The incidence and progression of this disease are influenced by many factors， particularly the change of intestinal flora. Previous research shows that the intestinal flora interacts with CRF. For CRF patients， the metabolic waste fails to be cleared in time due to the gradual decline of renal function and thus accumulates in vivo. Moreover， CRF changes the composition of intestinal flora， damages intestinal barrier， and accelerates the synthesis of intestinal uremic toxins and the accumulation in blood. As a result， the renal injury is aggravated. The imbalance of intestinal flora can induce acute kidney injury， increase cardiovascular complications， stimulate immune inflammatory responses， and thus aggravate the progression of CRF. Microbiota-targeted therapy for CRF has become the research focus. According to traditional Chinese medicine， kidney disease is related to the intestine and kidney disease should be treated from the intestine. Spleen and kidney are in the closest relationship with the pathogenesis of CRF and the intestinal flora. Chinese medicine， which features multiple targets， multiple effects， and multiple components， acts on the "gut-kidney axis". It is thus superior in the clinical treatment of CRF and the regulation of intestinal flora. To be specific， it intervenes in intestinal flora to delay the process of CRF. In this paper， based on the correlation of traditional Chinese medicine theory with intestinal flora and CRF， this paper reviewed the interaction between intestinal flora and CRF and traditional Chinese medicine intervention in the intestinal flora for the treatment of CRF， which is expected to serve as a reference for the clinical treatment of this disease and the drug development.

Role of Autophagy in Renal Interstitial Fibrosis and Intervention of Chinese Medicine： A Review / 中国实验方剂学杂志

Renal interstitial fibrosis（RIF）is a common pathway for the progression of chronic kidney disease to renal failure，and its pathogenesis is mainly related to renal inflammatory damage，oxidative stress，apoptosis，and excessive extracellular matrix（ECM） deposition. Transforming growth factor-β1（TGF-β1） signaling pathway，mammalian target of rapamycin（mTOR） signaling pathway and other signaling pathways mediate the occurrence and development of RIF. Because of the complicated mechanism of RIF，there have been no specific prevention and treatment measures in clinical practice. Autophagy is a non-damaging response produced by eukaryotic cells. It maintains the balance of tissue homeostasis through degradation and reabsorption. At present， Chinese medicine has achieved desirable clinical effects with its unique advantages of multiple components，multiple effects，and multiple targets in the treatment of chronic kidney disease to delay the process of RIF. Scholars have found that autophagy is consistent with the Yin-Yang theory and the theory of abdominal mass in traditional Chinese medicine （TCM） to a certain extent，and it is involved in many aspects of RIF. The progression of RIF is closely related to autophagy. The targeted therapy of RIF by intervention in autophagy has become the frontier of research. However，little is known about the role of autophagy in RIF and the regulation of autophagy by Chinese medicine in the treatment of RIF. Therefore，it is necessary to further elucidate the relationship between autophagy and RIF in order to clarify the mechanism of autophagy in RIF and the mechanism of Chinese medicine regulating autophagy in targeted therapy of RIF. This article focused on the correlation between autophagy and RIF based on TCM theory，and systematically summarized the role of autophagy in RIF and the intervention of Chinese medicine by combining the effects of autophagy on inflammation damage，oxidative stress，apoptosis，and excessive ECM deposition in RIF， and the regulation mechanism of autophagy in TGF-β1 and mTOR signaling pathways in RIF. This study was expected to provide a certain reference for the clinical treatment of RIF and the development of new drugs.

Role of Autophagy in Renal Interstitial Fibrosis and Intervention of Chinese Medicine： A Review / 中国实验方剂学杂志

Renal interstitial fibrosis（RIF）is a common pathway for the progression of chronic kidney disease to renal failure，and its pathogenesis is mainly related to renal inflammatory damage，oxidative stress，apoptosis，and excessive extracellular matrix（ECM） deposition. Transforming growth factor-β1（TGF-β1） signaling pathway，mammalian target of rapamycin（mTOR） signaling pathway and other signaling pathways mediate the occurrence and development of RIF. Because of the complicated mechanism of RIF，there have been no specific prevention and treatment measures in clinical practice. Autophagy is a non-damaging response produced by eukaryotic cells. It maintains the balance of tissue homeostasis through degradation and reabsorption. At present， Chinese medicine has achieved desirable clinical effects with its unique advantages of multiple components，multiple effects，and multiple targets in the treatment of chronic kidney disease to delay the process of RIF. Scholars have found that autophagy is consistent with the Yin-Yang theory and the theory of abdominal mass in traditional Chinese medicine （TCM） to a certain extent，and it is involved in many aspects of RIF. The progression of RIF is closely related to autophagy. The targeted therapy of RIF by intervention in autophagy has become the frontier of research. However，little is known about the role of autophagy in RIF and the regulation of autophagy by Chinese medicine in the treatment of RIF. Therefore，it is necessary to further elucidate the relationship between autophagy and RIF in order to clarify the mechanism of autophagy in RIF and the mechanism of Chinese medicine regulating autophagy in targeted therapy of RIF. This article focused on the correlation between autophagy and RIF based on TCM theory，and systematically summarized the role of autophagy in RIF and the intervention of Chinese medicine by combining the effects of autophagy on inflammation damage，oxidative stress，apoptosis，and excessive ECM deposition in RIF， and the regulation mechanism of autophagy in TGF-β1 and mTOR signaling pathways in RIF. This study was expected to provide a certain reference for the clinical treatment of RIF and the development of new drugs.

A single arm clinical study of 86 patients with common type of coronavirus disease 2019 treated by integrated traditional Chinese and Western medicine: multicenter case observation from 7 designated hospitals in Henan Province / 中华危重病急救医学

Objective:To evaluate the clinical effect of integrated traditional Chinese and Western medicine on common type of coronavirus disease 2019 (COVID -19) in Henan Province. Methods:A prospective single arm clinical study was performed. Patients with common type of COVID -19 admitted to seven designated hospitals for COVID -19 in Henan Province from January 25th to February 26th, 2020 were enrolled, and treated with integrated traditional Chinese and Western medicine. The negative transformation of 2019 novel coronavirus (2019 -nCoV) nucleic acid, disease outcome, hospital stay, clinical symptoms and signs scores, and chest imaging performance were observed. Results:Totally 86 cases were included in the analysis, including 48 males (55.8%), aged 43.5 (35.0, 53.3) years old, 24 patients (27.9%) with previous medical history. Fifty-eight patients were primarily diagnosed COVID -19 and 28 patients were transferred. The 2019 -nCoV nucleic acid of 86 cases (100%) turned negative, and the median time of turning negative was 10 (7, 14) days. Eighty-six cases (100%) were discharged from hospital, and none turned into the severe type; the average length of hospital stay was (13.8±5.6) days. The scores of fever, cough, chest tightness, shortness of breath, and fatigue decreased with the treatment time, and the scores of 7 days and 14 days after treatment were significantly lower than those before treatment [fever (points): 0 (0, 0), 0 (0, 0) vs. 1 (0, 1); cough (points): 1 (0, 1), 0 (0, 1) vs. 1 (0, 2); chest tightness (points): 0 (0, 0), 0 (0, 0) vs. 0 (0, 1); shortness of breath (points): 0 (0, 0), 0 (0, 0) vs. 0 (0, 1); fatigue (points): 0 (0, 1), 0 (0, 1) vs. 1 (0, 1); all P < 0.05]. The improvement rate of X ray and CT image was 42.9% (12/28) and 81.0% (64/79), respectively. Conclusions:The treatment with integrated traditional Chinese and Western medicine has good curative effect on common type of COVID -19 in 7 designated hospitals of Henan Province. It can improve the clinical symptoms, promote the absorption of pulmonary inflammation, and to some extent control the progress of disease and shorten the time of turning negative of virus nucleic acid and hospital stay.

Meta-analysis of single-group rate of the distribution of traditional Chinese medicine syndromes in 2 139 patients with coronavirus disease 2019 / 中华危重病急救医学

Objective:To systematically evaluate the incidence of coronavirus disease 2019 (COVID-19) syndrome in traditional Chinese medicine (TCM), and to provide a basis for the standard of COVID-19 syndrome differentiation.Methods:CNKI, China Medical Journal Network, PubMed and Embase databases were searched by computer, and TCM syndrome data of COVID-19 cross-sectional surveys and case series were collected from the establishment of the database to March 31st in 2020. Two researchers independently screened the literature, extracted relevant data such as TCM syndromes, and evaluated the quality of the literature according to the quality assessment tool recommended by the JBI Evidence-Based Health Care Center. Stata 14.0 software was used to perform a single-group Meta-analysis of TCM syndromes.Results:Thirteen cross-sectional studies and 5 case series studies were included, with a total of 2 139 patients. The analysis of the cross-sectional studies showed that the risk bias was higher in the identification, control and accuracy of the confounding factors, and the description of the reliability and validity of the outcome indicators was unclear. The analysis of the case series studies showed that the overall risk bias was small, but there was a lack of a comprehensive description of the assessment when selecting patients. A total of 33 TCM syndromes of COVID-19 were sorted out by combining the TCM syndromes with the same disease position and pathogenic syndrome in the included 18 literatures, and there were 10 types of TCM syndromes of which the number of occurrences was ≥50, the incidence rate was ≥10%, and had statistical significance [indicated that 95% confidence interval (95% CI) didn't cross the meaningless line 0], including cold dampness syndrome (469 cases, incidence rate was 28.2%, 95% CI was 5.9%-50.6%), damp heat syndrome (247 cases, incidence rate was 32.1%, 95% CI was 10.7%-53.6%), epidemic closed lung syndrome (228 cases, incidence rate was 28.9%, 95% CI was 12.5%-45.2%), pulmonary and spleen Qi deficiency syndrome (202 cases, incidence rate was 22.1%, 95% CI was 9.5%-34.7%), dampness stagnation lung syndrome (180 cases, incidence rate was 41.2%, 95% CI was 18.4%-64.1%), dampness obstructing lung and spleen syndrome (81 cases, incidence rate was 56.3%, 95% CI was 48.1%-64.4%), evil heat syndrome lung syndrome (76 cases, incidence rate was 31.1%, 95% CI was 25.3%-36.9%), dampness-blocking lung and stomach syndrome (70 cases, incidence rate was 13.4%, 95% CI was 10.4%-16.3%), heat poisoning lung closure syndrome (55 cases, incidence rate was 16.9%, 95% CI was 8.3%-25.5%), and Qi-Yin deficiency syndrome (53 cases, incidence rate was 13.7%, 95% CI was 2.7%-24.8%). Subgroup analysis showed that there were 6 types of TCM syndromes that met the above conditions in cross-sectional studies, namely cold and damp lung syndrome (200 cases, incidence rate was 20.9%, 95% CI was 12.6%-29.2%), damp heat syndrome (221 cases, incidence rate was 41.8%, 95% CI was 9.4%-74.2%), dampness-disease lung syndrome (120 cases, incidence rate was 41.4%, 95% CI was 8.6%-74.3%), lung and spleen Qi deficiency syndrome (115 cases, incidence rate was 19.2%, 95% CI was 6.8%-31.7%), heat-fever lung syndrome (76 cases, incidence rate was 31.1%, 95% CI was 25.3%-36.9%) and Qi-Yin deficiency syndrome (53 cases, incidence rate was 13.7%, 95% CI was 2.7%-24.8%). There were 3 kinds of TCM syndromes in case series studies, which were virus closed lung syndrome (133 cases, incidence rate was 44.0%, 95% CI was 24.5%-63.4%), lung and spleen Qi deficiency syndrome (87 cases, incidence rate was 38.7%, 95% CI was 32.3%-45.0%), and dampness and depression lung syndrome (60 cases, incidence rate was 40.6%, 95% CI was 29.3%-52.0%). Conclusions:The TCM syndromes of COVID-19 syndrome were widely distributed and complex. The main TCM syndromes were cold dampness syndrome, damp heat syndrome, epidemic closed lung syndrome, pulmonary and spleen Qi deficiency syndrome, dampness stagnation lung syndrome, dampness obstructing lung and spleen syndrome, evil heat syndrome lung syndrome, dampness-blocking lung and stomach syndrome, heat poisoning lung closure syndrome, Qi-Yin deficiency syndrome, which can provide reference for the standard of TCM syndrome differentiation of COVID-19.

Study on traditional Chinese medicine common syndrome characteristic of coronavirus disease 2019 based on latent structure combined with system clustering analysis / 中华危重病急救医学

Objective:To investigate traditional Chinese medicine (TCM) common syndrome characteristic of coronavirus disease 2019 (COVID-19), thus providing evidence for clinical differentiation.Methods:The COVID-19 TCM treatment plan and syndrome related literature published before February 24, 2020 was searched and a database was established. TCM common syndrome characteristics of COVID-19 were analyzed by the method of latent structure and system clustering combined with frequency and constituent ratio, which were conducted by Lantern 5.0 and SPSS 20.0.Results:Forty-two literatures about treatment plans, and 212 syndromes records were enrolled. Latent structure model was established based on 53 symptoms with frequency over 10, and 14 latent variables and 7 syndromes were concluded by comprehensive clustering, including syndrome of pathogenic heat invading lung, internal block and outward desertion, syndrome of dampness heat accumulating lung, syndrome of Qi and Yin deficiency, syndrome of epidemic virus closing lung, syndrome of cold dampness closing lung and syndrome of Qi deficiency of lung and spleen. Factor analysis was conducted for 53 symptoms, which were reported more than 10 times, and 14 common factors were obtained. Symptoms with load coefficient over 0.3 were clustered and 6 syndromes were obtained, including syndrome of epidemic virus closing lung, syndrome of pathogenic heat invading lung, syndrome of Qi and Yin deficiency, internal block and outward desertion, syndrome of cold dampness closing lung, and syndrome of dampness heat accumulating lung. The literatures included 25 syndromes, and the syndromes with constituent ratio over 5% were internal block and outward desertion (14.62%), syndrome of epidemic virus closing lung (13.68%), syndrome of dampness heat accumulating lung (12.74%), syndrome of Qi deficiency of lung (10.85%), spleen and syndrome of cold dampness closing lung (8.50%), syndrome of Qi and Yin deficiency (8.50%), syndrome of pathogenic heat invading lung (8.02%) and syndrome of dampness repressing defensive Qi of lung (5.66%). Eighty-seven symptoms whose cumulative frequency was 2 838 were referred, including greasy fur (5.25%), fever (4.83%), red tongue (4.37%), rapid pulse (3.74%) and fatigue (3.46%). According to the results above, the common syndromes and their symptoms of COVID-19 were: ① syndrome of pathogenic heat invading lung: fever, cough, throat-drying, headache, all of the body distressed and constipation, etc.; ② syndrome of cold dampness closing lung: aversion to cold, all of the body distressed, nausea and vomiting, abdominal distention and loose stool, etc.; ③ syndrome of dampness heat accumulating lung: cough, sticky phlegm, anorexia, thirst without desire to drink and constipation, etc.; ④ syndrome of epidemic virus closing lung: fever, cough, yellow phlegm, wheezing, suffocation and purple lips, etc.; ⑤ internal block and outward desertion: coma, feel fidgety, suffocation, sweating and feel cold and purple lips, etc.; ⑥ syndrome of Qi and Yin deficiency: dry cough, sweating, fatigue, thirsty, feverish feeling in palms and soles and loose stool, etc.; ⑦ syndrome of Qi deficiency of lung and spleen: cough, wheezing, sweating, fatigue, nausea and vomiting, and loose stool, et al.Conclusions:The common syndromes of COVID-19 were syndrome of pathogenic heat invading lung, syndrome of cold dampness closing lung, syndrome of dampness heat accumulating lung, syndrome of epidemic virus closing lung, internal block and outward desertion, syndrome of Qi and Yin deficiency and syndrome of Qi deficiency of lung and spleen. This study could provide reference for clinical differentiation.

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.

Effects of therapies for regulating and reinforcing lung and kidney on osteoporosis in rats with chronic obstructive pulmonary disease.

OBJECTIVE: To evaluate the efficacy and long-term effects of the three therapies for regulating and reinforcing lung and kidney (reinforcing lung and invigorating spleen, reinforcing lung and replenishing kidney, and supplementing Qi and nourishing kidney) in Traditional Chinese Medicine (TCM) on osteoporosis in rats with chronic obstructive pulmonary disease. METHODS: Totally 120 rats were randomly divided into control, model, Bufeijianpi, Bufeiyishen, Yiqizishen, aminophyline groups. Repeated smoke inhalations and bacterial infections were used to duplicate the stable Chronic obstructive pulmonary disease rat model. Normal saline was given to the air control and model groups, while Bufeijianpi granule, Bufeiyishen granule, and Yiqizishen granule, and aminophylline were administrated to rats in the Bufeijianpi, Bufeiyishen, Yiqizishen, and aminophylline groups respectively from weeks 9 through 20. Another 12 weeks without medicines to observe the long-term effect. Rats were sacrificed at week 20 and week 32. Bone mass density (BMD), bone mineral content (BMC), morphology of the femoral head, lung function, and levels of serum interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α were detected. RESULTS: At weeks 20 and 32, tidal volume, peak expiratory flow and expiratory flow at 50% tidal volume in the three TCM-treated groups were higher than those in the model group (P < 0.05). Femur weight, BMD, and BMC were significantly higher in the three TCM-treated groups and the aminophylline-treated group compared with the model group (P < 0.01), except for BMC in the Yiqizishen-treated group at week 20. CONCLUSION: Bufeijianpi, Bufeiyishen, and Yiqizishen granules show good effects in the prevention and treatment of osteoporosis, which can alleviate airflow limitations and inflammation, improve BMD and BMC of the femur, and have favorable long-term effects.

Study on Relationship between Atrophic Lung Disease and Modern Medicine Diseases on Experience of Famous Veteran Doctors of Traditional Chinese Medicine / 世界科学技术-中医药现代化

This study was aimed to explore the relationship between atrophic lung disease and modern medicine diseases through the study of experiences of modern famous doctors of traditional Chinese medicine (TCM) in the treatment of atrophic lung disease. Literatures which met the inclusion criteria were retrieved from the existing Lung Disease Database of Modern Famous Doctors of Chinese Medicineand Lung Disease Database of Journals for the establishment ofLiterature Research Database of Experience of Modern Famous Doctors of Chinese Medicine in Treating Atrophic Lung Disease. The SPSS 19.0 software was used in the statistical analysis. The results showed that atrophic lung disease can be interstitial lung disease, atelectasis, pneumonia, primary bronchogenic carcinoma, bronchiectasis, tuberculosis, chronic bronchitis and pneumothorax in modern medicine. Among them, interstitial lung disease was the most common one. It was concluded that atrophic lung disease can be the outcome of many types of lung diseases. The relationship between atrophic lung disease and modern medicine diseases should require further studies by experts to confirm.

Study of anti-cancer traditional Chinese medicine using systems biology technology / 中国肿瘤临床

This article focuses on the research of molecular mechanism of brain tumor treatment using the Jinlong capsule via system biology technology. Methods:Human Genome U133 Plus 2.0 gene chip was used to detect the genes of samples, in-cluding the brain tumor tissues of nude mice after Jinlong capsule intervention and those of blank control group mice. Differentially ex-pressed genes were identified based on fold change between the two groups. To identify the upstream regulators of the response signa-tures, the differentially expressed genes were subjected to interactome analysis by one-step overconnectivity test and multi-step hidden node algorithm. A set of genes preferentially connected to differentially expressed genes via direct interactions and pathways (called to-pologically significant genes) was generated. Concurrent pathway enrichment analysis on key pathways, processes, and functional units of both differentially expressed genes and topologically significant genes was performed to identify the most likely signaling pathways connecting regulators and effector genes. Finally, condition-specific networks (called causal network) were built to model molecular events by using a set of manually annotated protein interactions, pathways, and proteins and a toolkit of algorithms and filters on Meta-Core platform. Results:A total of 37 differentially expressed genes have been identified between Jinlong capsule-treated sample and ve-hicle sample with fold change of 2. Connection analysis identified 106 topologically significant genes. The main feature of the causal network is stimulation of neural cell specific genes that regulate normal cell physiology, particularly developmental processes and apop-tosis. Another important effect of the Jinlong capsule is its inhibition of the gene markers of interferon response, suggesting signaling in-hibition, followed by de-activation of immune response. Conclusion:Jinlong capsule exerts an anti-neoplastic effect by inducing stimu-lation of neural cell and by inhibiting interferon signal transduction.

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.

Influence on Glycolipid Metabolism, Neuron and Microvascular by Chinese Medicine Dai-Xie-An Granules among Aging Rats of Metabolic Syndrome / 世界科学技术-中医药现代化

This article was aimed to study the therapeutic effect of Chinese medicine Dai-Xie-A n (DXA) granules a-mong aging rats of metabolic syndrome (MS) in order to evaluate relative indicators and the pathophysiological role in neurons and microvascular injury among aging MS rats. Aging MS rat model was established by feeding high-fat diet and the established model was evaluated. Under the guidance of traditional Chinese medicine (TCM) theory, metabol-ic indexes, such as general state of health, glycolipid metabolism, insulin sensitivity, were explored in order to ob-serve effects on brain neurons and microvascular injury among aging MS rats. The results showed that DXA granules can improve glycolipid metabolism among aging MS rats, decrease TC, TG, TC/HDL, decrease the level of blood sug-ar and serum insulin, improve insulin resistance, decrease abdominal fat accumulation, reduce neuronal apoptosis, and increase microvascular angiogenesis. These effects are similar to rosiglitazone. It was concluded that DXA gran-ules can ameliorate glycolipid disorders, protect brain neurons and microvascular injury of aging MS rats.

Thinking on Key Technical Steps of Establishing on Curative Effect Evaluation Indexes for Traditional Chinese Medicine Syndromes under Disease-syndrome Combination Mode / 世界科学技术-中医药现代化

This paper was aimed to establish the curative effect evaluation indexes scientifically , which is the key technical step for the study of traditional Chinese medicine ( TCM ) effect evaluation methods under the mode of disease-syndrome combination. However, there is still a lack of generally accepted methods. In this paper , several key technical steps in the research process for establishing the curative effect evaluation indexes were put forward , namely , the framework of scientific and reasonable formation on the evaluation indexes is the premise; target selection of evaluation indexes is the core link; the evaluation and verification of evaluation in-dexes are key points , which provide the methodology reference for similar research in this field .

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.

Long-term effects of Tiaobu Feishen therapies on systemic and local inflammation responses in rats with stable chronic obstructive pulmonary disease / 中西医结合学报

To evaluate the influence and long-term effects on systemic and local inflammation responses in rat with stable chronic obstructive pulmonary disease (COPD) treated with traditional Chinese medicine (TCM) for regulating and invigorating the lung and kidney, including invigorating the lung and spleen (Bufei Jianpi) therapy, supplementing the lung and kidney (Bufei Yishen) therapy, and nourishing qi and kidney (Yiqi Zishen) therapy.