[Effect of Modified Zhisou Powder on the lung function of chronic obstructive pulmonary disease model rats of northwest China cold dryness syndrome].

OBJECTIVE: To observe Modified Zhisou Powder (MZP) on the lung function of chronic obstructive pulmonary disease (COPD) model rats of northwest China cold dryness syndrome (NCCDS). METHODS: Totally 90 male Wistar rats were randomly divided into three groups, i.e., the normal control group (n =20), the COPD model group (n =35), and the COPD of NCCDS group (n =35). The COPD model was established by tracheal dripping porcine pancreatic elastase (PEE) in combination with fumigation for 90 days. The COPD of NCCDS model was set up by tracheal dripping PEE +fumigation + cold and dry environmental stress for 90 days. Then rats in the COPD of NCCDS were randomly divided into the MZP intervention group (n =11 )and the normal saline intervention group (n =10).All intervention lasted for 15 successive days. The lung function was detected using Small Animal Lung Function Device at day 90 and day 105. And the lung pathology was also observed. RESULTS: Little amount of sputum sound could be heard in the airway of the COPD model group and the COPD of NCCDS group. Pathological section showed alveolar ectasia, narrowed and broken alveolar septa, forming larger capsular space with infiltration of inflammatory cells. Rats in the COPD of NCCDS group showed chills, increased amount of drinking water, and loose stool. MZP could improve their symptoms. As for lung function test, compared with the normal control group, Te increased in the COPD model group (P <0.01), and EF50 decreased (P<0.05). PEF and EF50 decreased (P <0.01), Ti and Te increased (P <0.01, P <0.05) in the COPD of NCCDS group. Compared with the normal saline intervention group, PEF and EF50 increased (P < 0.01), Ti and Te decreased (P <0.01) in the MZP intervention group. CONCLUSION: MZP could improve the symptoms of COPD rats of NCCDS, and delay the velocity of decreased lung function.

[The anti-apoptotic effect of cytoplasmic alpha-fetoprotein in hepatoma cells induced by all-trans retinoic acid involves activation of the PI3K/AKT signaling pathway].

OBJECTIVE: To explore the effect of alpha-fetoprotein (AFP) on transduction of the PI3K/ AKT signal in hepatocellular carcinoma cells and the role played by AFP in resistance to cytotoxicity of all-trans retinoic acid (ATRA). METHODS: The effects of ATRA of human liver cancer cells was assessed using the BEL-7402 cell line with the MTT assay (to evaluate proliferation), microscopy (to evaluate morphology), flow cytometry (to evaluate apoptosis), laser confocal microscopy and coimmunoprecipitation (co-IP; to evaluate co-localization and interaction of AFP with PTEN), Western blotting (to evaluate expression of phosphorylated-protein kinase B (pAKT) and Src, and RNA interference (RNAi)-mediated knockdown of AFP. Finally, application of the PI3K-specific inhibitor Ly294002 was used to monitor the influence of AFP in transduction of the PI3K signal pathway. RESULTS: The human hepatoma cell line BEL-7402 were resistant to ATRA cytotoxicity. PTEN and AFP co-localized in the cytoplasm, and co-IP indicated that AFP interacts with PTEN in BEL-7402 cells.RNAi knockdown of AFP expression led to reduced growth of BEL-7402 cells.BEL-7402 cells transfected with AFP-short interfering (si)RNA vectors showed enhanced sensitivity to ATRA and reduced expression of pAKT(Ser473) and Src; Ly294002 reduced the role of AFP in stimulating expression of pAKT(Ser473) and Src. CONCLUSION: AFP can activate transduction of the PI3K/AKT signal, and expression of AFP in hepatoma cells is a pivotal event for resisting ATRA-induced apoptosis.

Yiqigubiao pill treatment regulates Sirtuin 5 expression and mitochondrial function in chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous group of pathophysiological bases of airway inflammation and its anti-inflammatory response. Aberrant mitochondrial signaling and mitochondrial dysfunction underlie the pathomechanisms leading to COPD. This study aims to investigate the effects of the Yiqigubiao (YQGB) pill, a traditional Chinese medicine (TCM), on Sirtuin 5 (SIRT5) and mitochondrial function in patients with COPD. Methods: Thirty-four patients with COPD were randomized into oral YQGB or placebo groups concurrent with a 24-week routine treatment. The pulmonary function was assessed by examining the levels of forced expiratory volume in one second (FEV1)/forced vital capacity (FVC), FEV1, and FVC. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect SIRT5 expression in mitochondria isolated from peripheral blood. Flow cytometry was used to detect changes in mitochondrial membrane potential and reactive oxygen species (ROS) in peripheral blood lymphocytes. Human bronchial epithelial (HBE) cells stimulated by cigarette smoke extract (CSE) were treated with YQGB. After SIRT5 was knocked down in cells, the changes in mitochondrial membrane potential, levels of adenosine triphosphate (ATP), and ROS were detected. Results: YQGB treatment significantly improved lung function in patients with COPD. The expression of SIRT5 and the mitochondrial membrane potential significantly increased and ROS decreased in patients with COPD after YQGB treatment. The CSE decreased cell proliferation and SIRT5 expression, which was alleviated after YQGB treatment. Furthermore, SIRT5 was knocked down in CSE-stimulated HBE cells, and its expression was elevated upon YQGB treatment. The knockdown of SIRT5 significantly altered the CSE-stimulation-induced dysregulation of mitochondrial membrane potential, ATP levels, and ROS. This was also restored after YQGB treatment. Conclusions: YQGB treatment can elevate SIRT5 expression, restore mitochondrial function in COPD, and exert protective effects.

Inflammatory responses of the rat lungs in cold-dryness syndrome in the northwest of China.

OBJECTIVE: To examine changes in body weight and the lung inflammation factors interleukin-1beta (IL-1beta), interleukin-8 (IL-8), IL-10 and tumor necrosis factor-alpha (TNF-alpha) in a rat model of cold-dryness syndrome in Northwest (Xinjiang) China to provide a reference for treating chronic obstructive pulmonary disease (COPD) with local peculiarities. METHODS: The rat COPD model was established by intratracheal instillation of porcine pancreatic elastase (PPE) in combination with cigarette smoking (CS). The rat model of cold-dryness syndrome of COPD in the northwest of China was set up by intratracheal instillation of PPE in combination with CS and environmental cold-dryness stress. The level of IL-1beta, IL-8, IL-10 and TNF-alpha in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). The data were analyzed using the software SPSS 11.5. RESULTS: (1) Body weight was less in the two model groups than that of control group (P < 0.01), PPE plus CS cold-dryness group was less than that of PPE plus CS group (P < 0.01). (2) IL-1beta in BALF significantly increased in PPE plus CS and cold-dryness group than that of control group (P < 0.01). (3) IL-8 and TNF-alpha in BALF significantly increased in PPE plus CS and cold-dryness group and PPE plus CS group than that of control group (P < 0.01). CONCLUSION: Body weight in COPD model rats was reduced compared with controls. Cold-dryness may aggravate such a condition lung inflammation in the model was mainly manifested by an increase in IL-1beta, IL-8 and TNF-alpha levels, with no change in IL-10 levels. Cold-dryness may aggravate lung inflammation of COPD.

[The expressions of TNF-alpha and MMP-9 in serum and MMP-1 mRNA in the bone tissue in chronic obstructive pulmonary disease patients of cold dryness syndrome in northwest China].

OBJECTIVE: To observe the expressions of tumor necrosis factor a (TNF-alpha) and matrix metalloproteinase (MMP-9) in serum and matrix metalloproteinase 1 (MMP-1) mRNA in the bone tissue in chronic obstructive pulmonary disease (COPD) patients of cold dryness syndrome (CDS) in northwest China, thus providing reference for wholism treating COPD of CDS. METHODS: Twenty-one male Wistar rats were randomly divided into three groups, i.e., the normal control group, the COPD model group, and the COPD of CDS group, 7 in each group. The COPD model was established by dripping porcine pancreatic elastase (PEE) in trachea combination with cigarette smoking, and the COPD of CDS model was also set up by dripping PEE in trachea in combination with cigarette smoking and cold-dry environmental stress. Serum contents of TNF-alpha and MMP-9 were determined using ELISA. The MMP-1 mRNA expression in rats' bone tissue was detected using fluorescent quantitative PCR. RESULTS: Compared with the normal control group, the serum MMP-9 level obviously increased in the COPD of CDS group (P < 0.05). The MMP-1 mRNA expression level in the bone tissue of the COPD of CDS group and the COPD model group also obviously increased (P < 0.01, P < 0.05). The MMP-1 mRNA expression level was obviously higher in the COPD of CDS group than in the COPD model group (P < 0.01). There was no statistical difference in the serum TNF-alpha level among the three groups (P > 0.05). CONCLUSION: CDS could increase the serum MMP-9 level and the MMP-1 mRNA expression in the bone tissue, which might be one of reasons for the fact that cold and dry environment causes more bone resorption and bone degradation in COPD.

A study of the law of herbal administration in treating lung-distension by TCM physicians through history using cluster analysis.

OBJECTIVE: To review the herbal drugs used most often for treating lung-distension by determining those used by physicians throughout history; to study their property, taste, and channel tropism; and to explore their compatibility. METHODS: Historical prescriptions for treating lung-distension were collected and sorted. Property, taste and channel tropism were determined, and the law of herbal administration was determined by cluster analysis. RESULTS: One hundred and ninety five prescriptions were found, involving 166 herbal drugs, with a total appearance frequency of 1296 drugs. The herbs involved 8 properties (total appearance frequency, 1296), 7 forms of taste (total appearance frequency, 1991) and involved all 12 regular channels (total appearance frequency, 3382). Sixteen herbal drugs were used most often and formed 4 cluster prescriptions: C1: Xing Ren (Semen Armeniacae Amarum), Gan Cao (Radix Glycyrrhizae), and Ban Xia (Rhizoma Pinelliae); C2: Gui Zhi (Ramulus Cinnamomi), Wu Wei Zi (Fructus Schisandrae), and Sheng Jiang (Rhizoma Zingiberis Recens); C3: Da Zao (Fructus Jujubae), Ma Huang (Herba Ephedrae), and Shi Gao (Gypsum Fibrosum); and C4: Chen Pi (Pericarpium Citri Reticulatae), Jie Geng (Radix Platycodi), Fu Ling (Poria), Sang Bai Pi (Cortex Mori), Xi Xin (Herba Asari), Gan Jiang (Rhizoma Zingiberis), and Bai Shao (Radix Paeoniae Alba). CONCLUSION: In treating lung-distension, phlegm retention has been traditionally considered the underlying pathology, emphasizing regulation of the lung and spleen as key and stressing patient nourishment and mental improvement. Prescriptions for lung-distension should be made with reference to the property, taste, channel tropism, and effectiveness of the chosen herbal drugs.

Development and Assessment of Prediction Models for the Development of COPD in a Typical Rural Area in Northwest China.

OBJECTIVE: This study aimed to construct and evaluate a clinical predictive model for the development of COPD in northwest China's rural areas. METHODS: A cross-sectional study of a natural population was performed in rural northwest China. After assessing demographic and disease characteristics, a clinical prediction model was developed. First, we used the least absolute shrinkage and selection operator regression model to screen possible factors influencing COPD. Then construct a logistic regression model and draw a nomogram. The discriminability of the model was further evaluated by the calibration diagram, C-index and ROC curve system. Clinical benefit was analyzed using the decision curve. Finally, the 1000 bootstrap resamples and Harrell's C-index was used for internal verification of the nomogram. RESULTS: Among 3249 patients in the local rural natural population, 394 (12.13%) were diagnosed with COPD. The LASSO regression model was used to find the optimal combination of parameters, and the screened influencing factors included age, gender, barbeque, smoking, passive smoking, energy type, ventilation system and Post-Bronchodilator FEV1. These predictors are used to construct a nomogram. C index is 0.81 (95% confidence interval:0.79-0.83). The combination of the calibration curve and ROC curve indicates that the model has high discriminability. The decision curve shows benefits in clinical practice when the threshold probability is >6% and <58%, respectively. The internal verification results using Harrell's C-Index were 0.80 (95% confidence interval: 0.78-0.83). CONCLUSION: Combining information such as age, sex, barbeque, smoking, passive smoking, type of energy, ventilation systems, and Post-Bronchodilator FEV1 can be easily used to predict the risk of COPD in local rural areas.

Differences in key genes in human alveolar macrophages between phenotypically normal smokers and nonsmokers: diagnostic and prognostic value in lung cancer.

OBJECTIVE: To explore the effect of smoking on gene expression in human alveolar macrophages and the value of identified key genes in the early diagnosis and prognosis of lung cancers. METHODS: We downloaded three data sets (GSE8823, GSE2125, and GSE3212) from the Gene Expression Omnibus (GEO) database, including 31 non-smoking and 33 smoking human alveolar macrophage samples. We identified common differentially expressed genes (DEGs), from which we obtained module genes and hub genes by using STRING and Cytoscape. Then we analyzed the protein-protein interaction (PPI) network of DEGs, hub genes, and module genes and used David online analysis tool to carry out functional enrichment analysis of DEGs and module genes. RESULTS: A total of 85 differentially expressed genes was obtained, including 42 up-regulated genes and 43 down-regulated genes. The Human Protein Atlas and Survival analysis showed that GBP1, ITGAM, CSF1, SPP1, COL1A1, LAMB1 and THBS1 may be closely associated with the carcinogenesis and prognosis of lung cancer. CONCLUSION: DEGs, module, and hub genes identified in the present study help explain the effects of smoking on human alveolar macrophages and provide candidate targets for diagnosis and treatment of smoking-related lung cancer.

Integrated Analysis of a Gene Correlation Network Identifies Critical Regulation of Fibrosis by lncRNAs and TFs in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF), the most frequent form of irreversible interstitial pneumonia with unknown etiology, is characterized by massive remodeling of lung architecture and followed by progressive loss of lung function. However, the key regulatory genes and the specific signaling pathways involved in the onset and progression of IPF still remain unclear. The present study is aimed at investigating the key role of long noncoding RNAs (lncRNAs) and transcription factors (TFs) involved in the pathogenesis of IPF through the integrated analysis of three gene expression profiles from the GEO dataset (GSE2052, GSE44723, and GSE24206). A total of 8483 differentially expressed genes (DEGs) including 988 upregulated and 7495 downregulated genes were filtered. Subsequently, following the intersection of these DEGs, 29 overlapping genes were identified and further analyzed using a bioinformatics approach. Furthermore, the protein-protein interaction (PPI) network was used to obtain 18 modules of related genes. The hub genes were identified through hypergeometric testing, which were closely associated with ubiquitin-mediated proteolysis, the spliceosome, and the cell cycle. The significant difference was observed in the expression of these key genes, such as lncRNA MALAT1, E2F1, and YBX1, in the peripheral blood of IPF patients when compared with those normal control subjects by real-time polymerase chain reaction (RT-PCR) analysis. This study indicated that lncRNA MALAT1, E2F1, and YBX1 may be key regulators for the pathogenesis of IPF.

Prognostic role of C-reactive protein to albumin ratio in colorectal cancer: A meta analysis.

OBJECTIVE: This meta-analysis evaluates the prognosis value of C-reactive protein to albumin ratio (CAR) in colorectal cancer. METHODS: Embase, PubMed, and Web of Science were searched. Pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were used as effective values. RESULTS: A total of 6 studies with 1942 patients were included in this study. Pooled results revealed that elevated pretreatment CAR was related with poorer overall survival (OS) (HR: 2.09, 95%CI: 1.78-2.45, P < .001) in colorectal cancer. CONCLUSION: Elevated CAR was associated with poor prognosis in colorectal cancer. Thus CAR might be used as a prognostic system and classification of colorectal patients in clinical potential.

[Mahuang Zhisou Capsule in treatment of acute upper respiratory tract infection of external wind-cold syndrome: a multi-center, randomized controlled, and double-blind trial].

OBJECTIVE: To evaluate the efficacy and safety of Mahuang Zhisou Capsule (MHZSC), a compound traditional Chinese herbal medicine, in treatment of acute upper respiratory tract infection of wind-cold syndrome. METHODS: A multi-center, double-blind, double dummy, randomized controlled trial was conducted. A total of 240 patients were randomized into treatment group (120 cases, treated with MHZSC) and control group (120 cases, treated with Mahuang Zhisou Pill). The therapeutic course was 3 days. RESULTS: Seven cases were excluded and three cases lost to follow-up. Two hundred and thirty-three cases entered intention-to-treat (ITT) analysis and 230 cases fitted in per-protocol population set (PPS) analysis. After treatment, the therapeutic effect of upper respiratory tract infection was calculated by ITT and PPS analysis respectively. The significant response rate and total response rate in the treatment group were 78.07% and 98.25% (ITT and PPS), while the significant response rates in the control group were 70.59% (ITT) and 70.69%(PPS), and the total response rates were 95.80% (ITT) and 95.69% (PPS) respectively. There were no significant differences in clinical efficacy between the two groups (P>0.05). CONCLUSION: MHZSC is effective and safe in treatment of acute upper respiratory tract infection of external wind-cold syndrome.

An evaluation of activity tolerance, patient-reported outcomes and satisfaction with the effectiveness of pulmonary daoyin on patients with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Pulmonary Daoyin (PD) (evolved from ancient Chinese daoyin skills), is a rehabilitation technology that combines specially designed movements of the arms and body and controlled breathing exercises, to improve the physiological and psychological status of patients with chronic respiratory disease. Pulmonary rehabilitation is effective for patients with chronic obstructive pulmonary disease (COPD), and the efficacy of PD is unknown. The aim of this study is to investigate the effect of a PD program in enhancing activity tolerance, patient-reported outcomes and satisfaction with the effectiveness on patients with COPD. MATERIALS AND METHODS: The multi-center, randomized controlled trial was conducted from November 2011 to June 2012 in local communities in cities of the 11 research centers in China. It included COPD patients (moderate to very severe) who were recruited from an outpatient clinic. A randomized controlled study included 464 COPD patients who were randomly allocated either to the PD group, participating in a 3-month, ten times-weekly supervised PD-based pulmonary rehabilitation program, or to a control group continuing with regular medical treatment alone. Data were gathered using the 6-minute walking distance (6MWD) test, COPD patient-reported outcomes (COPD-PRO) and Effectiveness Satisfaction Questionnaire for COPD (ESQ-COPD), which was filled out at baseline and 3 months post-intervention. SAS 9.2 was used for statistical analysis. RESULTS: Of the 464 patients in the study, 461 were included in the full analysis set (FAS); 429 were in the per-protocol analysis set (PPS). After 3-month intervention, there was a significant difference between the two groups in 6MWD (FAS; P=0.049; PPS; P=0.041), total score and all domains of COPD-PRO (FAS; P=0.014; PPS; P=0.003) and ESQ-COPD (FAS; P=0.038; PPS; P<0.001). CONCLUSIONS: The PD program was able to improve the activity tolerance level and satisfaction of COPD patients because of its effectiveness.

Inhibition of Asthma in OVA Sensitized Mice Model by a Traditional Uygur Herb Nepeta bracteata Benth.

Asthma is a chronic lung inflammation which affects many people. As current therapies for asthma mainly rely on administration of glucocorticoids and have many side effects, new therapy is needed. In this study, we investigated Nepeta bracteata Benth., a traditional Uygur Herb, for its therapeutics effect in OVA induced asthmatic mice model. Treatment of OVA sensitized asthma mice with extract from Nepeta bracteata Benth. demonstrated improved lung pathology, as well as reduced infiltration of eosinophil and neutrophil. Nepeta bracteata Benth. extract also contributed to the rebalance of Th17/Treg cell via decreasing the Th17 cell and increasing the Treg, which was corresponding with the inhibited Th17 cytokine response and increased IL-10 level. Moreover, the reduced TGF-ß level and Smad2/3 protein level also suggested that Nepeta bracteata Benth. extract could inhibit TGF-ß mediated airway remodelling as well. Taken together, these data suggested that Nepeta bracteata Benth. may be a novel candidate for future antiasthma drug development.

Randomized, double-blind, placebo-controlled superiority trial of the Yiqigubiao pill for the treatment of patients with chronic obstructive pulmonary disease at a stable stage.

In traditional Chinese medicine (TCM), the Yiqigubiao pill is commonly used to enhance physical fitness. The current clinical trial was designed to evaluate the efficacy and safety of the Yiqigubiao pill as an adjuvant therapy for patients with stable chronic obstructive pulmonary disease (COPD). The current trial was a randomized, double-blind, placebo-controlled superiority trial. The participants were recruited from outpatients at the Traditional Chinese Medicine Hospital affiliated with Xinjiang Medical University (Ürümqi, China) between February and September 2012. All participants were patients with stable COPD that were randomized to the Yiqigubiao pill (YQGB; n=84) or placebo (Pb; n=87) groups. The occurrences of acute exacerbation (AE) of COPD during the trial were recorded. Lung function value assessments, scoring of life quality and exercise endurance, arterial blood gas analysis and serum inflammatory cytokines level determination were performed prior to and throughout the study. A total of 139 participants completed the intervention and 132 participants completed the study. The interval between the initial intervention and the first AECOPD was greater in the YQGB group compared with the Pb group (P<0.01). The incidence rate of AECOPD was lower in the YQGB group than in the Pb group (P<0.01). Subsequent to the intervention or at the end of the study, the 6-min walking distance difference was longer in the YQGB group compared with the Pb group (P<0.01). The scores reflecting life quality decline became lower in the YQGB group (P<0.01). The serum levels of proinflammatory factors were downregulated to a greater extent in the YQGB group compared with the Pb group. Thus, the Yiqigubiao pill is an efficient and safe adjuvant therapy for the treatment of stable patients with COPD.

Expression of aquaporins in the lungs of mice with acute injury caused by LPS treatment.

The aim of the present study was to investigate the expression of aquaporin 1 (AQP1) and AQP5 in the lungs of mice with acute injury induced by LPS treatment. In the study, the concentrations of cytokines were all significantly increased in the BALF of mice received LPS at 12h and 24h (P<0.001). The lung wet/dry weight ratios (W/D) and total protein content in BALF were also increased in the mice treated with LPS (P<0.001). Interestingly the expression of AQP1 and AQP5 was significantly decreased (P<0.05) compared with these in the control mice, while TUNEL positive cells were increased. However, the AQP5 expression was significantly higher at 24h that it at 12h in the control mice. Our results showed that decreased AQP expression was associated with the increased inflammatory factors, as well as apoptotic cells. The increased expression of AQP5 at 24h in control mice might be due to its regulation in transcellular water reabsorption.

Chinese herbs in treatment of influenza: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To investigate the efficacy and safety of Antiwei, a traditional Chinese prescription, in the treatment of influenza. METHODS: In a multi-center, randomized, double-blind, placebo-controlled trial, we recruited 480 adults aged 18 to 65 years within 36 h of onset of influenza-like symptoms. There were 225 patients with confirmed influenza. Eligible patients were randomly assigned 6 g of Antiwei (n = 360) or placebo (n = 120) twice daily for three days. All patients recorded their temperature and symptoms on diary cards during treatment. Analyses were performed in both the influenza-like population and the influenza-confirmed population. RESULTS: Antiwei increased patients' recovery by 17% (P < 0.001), and reduced the severity of illness measured by the median symptom score by 50% (P < 0.001) in both the influenza-like and the influenza-confirmed populations, compared to placebo. The influenza-confirmed patients reported reductions in the severity of fever (P = 0.002), cough (P = 0.023) and expectoration (P = 0.004) after one-day of treatment with Antiwei, compared to placebo. The adverse event profiles were similar for Antiwei and placebo. CONCLUSION: Antiwei was effective and well tolerated in treatment of natural influenza infection in adults. Antiwei represents a clinically valuable intervention in the management of influenza.