[Analysis of animal models of stable chronic obstructive pulmonary disease based on clinical features of traditional Chinese medicine and western medicine].

This study analyzed the advantages and disadvantages of existing animal models in China and abroad and their goodness of fit based on the clinical characteristics and diagnostic criteria of stable chronic obstructive pulmonary disease(COPD) in traditional Chinese medicine(TCM) and western medicine, followed by the collation and summarization of model evaluation methodologies. The results showed that the existing animal models of stable COPD were mainly modeled via smoke exposure or the combination of multiple methods like smoke exposure plus lipopolysaccharide or protease or bacterial infection. These animal models generally failed to simulate the clinical characteristics of TCM, and their goodness of fit in western medicine was higher than that in TCM. There is a lack of research on the animal models of stable COPD and the disease-syndrome combination models. Although the modeling is guided by the pathogenesis or mechanism of diseased humans, the established models were still not identical with the actual clinical situations. In-depth research is needed to develop quantitative standards for stable COPD models.

Wentong decoction cures allergic bronchial asthma by regulating the apoptosis imbalance of EOS.

BACKGROUND: Eosinophils (EOS) is one of the most important cells involved in the pathogenesis of chronic airway inflammation in asthma, and its apoptosis is part of the mechanisms of asthma. Therefore, this study aimed to observe the effect of Chinese medicine Wentong decoction (WTD) in EOS apoptosis in asthmatic rats. This work also explored the mechanism of WTD regulation in EOS apoptosis and provided a new target for clinical treatment of asthma. METHODS: Asthmatic rats induced by ovalbumin were treated with WTD. Lung function of rats in each group was detected, and lung tissue pathology, EOS counts in blood and bronchoalveolar lavage fluid were observed. The degree of the EOS apoptosis in rats was detected. The expression content of interleukin (IL)-5, IL-10, chemokine (C-C motif) ligand 5 (CCL5), granulocyte-macrophage colony-stimulating factor (GM-CSF), transforming growth factor beta 1 (TGF-ß1), interferon (IFN)-γ, and other cytokines in rat serum and the genes of Eotaxin mRNA, Fas mRNA, FasL mRNA, Fas/FasL and Bcl-2 mRNA in the lung tissues were determined. RESULTS: WTD can reduced airway resistance in rat models and improved airway compliance. The pathological changes of lung tissue in WTD group were significantly alleviated, at the same time, WTD could reduce the EOS count in the blood and BALF smears of the asthmatic model rats. Compared with the model group, the apoptosis degree of EOS significantly increased in rats in the WTD group. The expression of IL-5, CCL5, and GM-CSF in the serum and the expression of Eotaxin mRNA, Bcl-2 mRNA in the lung tissues in rats in the WTD group rats decreased. Moreover, the expression of IL-10, TGF-ß1, and IFN-γ in the serum and the expression of Fas mRNA, FasL mRNA in the lung tissues in rats in the WTD group rats increased compared with that in rats in the model group. CONCLUSIONS: Wentong decoction may accelerate EOS apoptosis, reduce asthma inflammation, and alleviate the disease through regulating and controlling the factors related to the anti-apoptosis and pro-apoptosis.

Structural Modulation of Gut Microbiota in Rats with Allergic Bronchial Asthma Treated with Recuperating Lung Decoction.

OBJECTIVE: To investigate whether recuperating lung decoction (RLD) can modulate the composition of gut microbiota in rats during asthma treatment. METHODS: Fifteen Sprague-Dawley rats were divided randomly and equally into control group, model group, dexamethasone (DEX) group, RLD medium-dose group, and RLD high-dose group. The asthma model was established in all groups, except for the control group. The rats in the DEX and RLD groups were treated orally with DEX and RLD, respectively. The rats in the control and model groups were treated orally with 0.9% saline. The intestinal bacterial communities were compared among groups using 16S rRNA gene amplification and 454 pyrosequencing. RESULTS: The microbial flora differed between the control and model groups, but the flora in the RLD groups was similar to that in the control group. No significant differences were observed between the RLD high-dose and medium-dose groups. RLD treatment resulted in an increase in the level beneficial bacteria in the gut, such as Lactobacillus and Bifidobacterium spp. CONCLUSION: Oral administration of RLD increased the number of intestinal lactic acid-producing bacteria, such as Lactobacillus and Bifidobacterium, in asthma model rats.

Flax seed oil inhibits metastatic melanoma and reduces lung tumor formation in mice.

PURPOSE: Cancer is one of the leading causes of mortality worldwide. Tumor cells circulating in the blood evidence the migration of tumor from the site of origin to another site leading to the formation of new metastatic lesion and establishment of metastatic tumors. In the present study, cultured metastatic tumor cells were injected into the C57BL/6 mice through tail-vein injection (TVI) and the anti-metastatic properties of flax seed oil (FSO) were evaluated. METHODS: Pre-administration of FSO in a dose of 0.3 ml/mice/day was performed for 15 days. On 16th and 21st day, mice were challenged with 2x105 /100 µl murine B10 melanoma (YAC-1 suspended in sterile PBS) cells and continued with FSO administration until the end of the experimental period (40 days) to assess the effect on lung metastasis. At the end of experimental period, mice were sacrificed for plasma and lung tissue samples for biochemical and marker studies. Activities of marker enzymes (AST and ALT), enzymic antioxidants (superoxide dismutase/SOD and catalase/CAT), levels of non/enzymic antioxidants (glutathione), oxidation/stress marker (malondialdehyde/MDA) and cytokines (TNF-alpha, IL-2, IFN-gamma and MMP-9) were assessed. RESULTS: Elevated marker enzyme activities in serum and altered enzymic and non-enzymic antioxidants were recovered during FSO treatment. Altered metastatic markers levels favoring the formation of metastatic lesions were observed in the disease group. FSO administration re-altered the levels of these markers in the treatment group contributing to better control of metastasis development. CONCLUSION: These results support the protective role of FSO against lung cancer metastasis.

Studies of the microbial metabolism of flavonoids extracted from the leaves of Diospyros kaki by intestinal bacteria.

Flavonoid glycosides are metabolized by intestinal bacteria, giving rise to a wide range of phenolic acids that may exert systemic effects in the body. The microbial metabolism of flavonoids extracted from the leaves of Diospyros kaki (FLDK) by intestinal bacteria was investigated in vitro. High-performance liquid chromatography/linear trap quadrupole orbitrap mass spectrometry was performed to analyze the metabolites of flavonoids in vivo using Xcalibur2.1 software. The results showed that the levels of flavonoid glycosides and flavonoid aglycones decreased rapidly in the process of microbial metabolism by intestinal bacteria in vitro, and the metabolic rate may be related to the concentration of intestinal bacteria in the culture solution. In vivo metabolites of FLDK were detected in rat plasma and urine after oral administration of FLDK. Eight flavonoids were identified in the urine, and three were identified in the plasma; however, flavonoid aglycones were not found in the plasma.

[Development of a patient-reported outcome scale for stable chronic obstructive pulmonary disease and its clinical applicability].

OBJECTIVE: To develop a patient-reported outcome (PRO) scale for patients with stable chronic obstructive pulmonary disease (sCOPD) and to study its clinical applicability in traditional Chinese medicine (TCM). METHODS: According to standardized procedures, the test version of PRO scale for sCOPD (sCOPD-PRO scale) was developed based on the theory of "unity of body and spirit" and was used to test 324 patients selected from six clinical centers. Five methods were used to analyze the items; the reliability, validity and responsiveness of the remaining items of the scale were evaluated. RESULTS: (1) sCOPD-PRO consisted of 23 items after item analysis, and according to the content of each item, these items could be grouped into four domains, namely, lung and kidney deficiency symptom, spleen deficiency symptom, functional activities and emotional impact. (2) Cronbach's alpha coefficient for sCOPD-PRO scale was more than 0.75 in four domains and total scores. (3) sCOPD-PRO scale and St. George's Respiratory Questionnaire (SGRQ) were moderately correlated or highly correlated in corresponding domains: the correlation coefficient between the total score of sCOPD-PRO scale and the total score of SGRQ was 0.72 (P<0.01), the correlation coefficient between functional activities domain of sCOPD-PRO scale and activity domain of SGRQ was 0.77 (P<0.01), and the correlation coefficient between emotional impact domain of sCOPD-PRO scale and impact domain of SGRQ was 0.51 (P<0.01). Factor analysis revealed that four factors could explain 65.06% of the total variance. (4) The four domains and total scores of sCOPD-PRO scale were significantly different before and after intervention in TCM group and Western medicine group (P<0.01); moreover, the effect size and standardized response mean of two groups were more than 0.4. CONCLUSION: The development process and method of sCOPD-PRO scale, which is based on the theories of "unity of body and spirit", are standard, and the reliability, validity and responsiveness of the scale are sound and can be relied upon for sCOPD clinical efficacy evaluation of TCM.

[Diagnostic significance of multi-slice computed tomography imaging in congenital inner ear malformations].

OBJECTIVE: To evaluate the feasibility and usability of multi-slice computed tomography (MSCT) in congenital inner ear malformations. METHODS: Fourty-four patients with sensorineural hearing loss (SNHL) were examined by a Somatom Sensation 16 (siemens, Germany) CT scanner with following parameters: 120 kV, 100 mAs, 0.75 mm collimation, 1 mm reconstruction increment, a pitch factor of 1 and a field of view of 100 mm. The axial images of interested ears were reconstructed with 0.1 mm reconstruction increment, and a field of view of 50 mm. The 3D reconstructions were done with volume rendering technique (VRT) on the workstation (3D Virtuoso and Wizard,siemens). RESULTS: Twenty-five patients were normal and 19 patients (36 ears) were congenital inner ear malformations among 44 patients scanned with MSCT. Of the malformations, all the axial, MPR and VRT images can display the site and degree in 33 ears. VRT images were superior to the axial images in displaying the malformations in 3 ears with the small lateral semicircular canal malformations. The malformations were Michel deformity (1 ear), common cavity deformity (3 ears), incomplete partition I (3 ears), incomplete partition II (Mondini deformity, 5 ears), vestibular and semicircular canal malformations( 14 ears), vestibular aqueduct dilate( 16 ears, of which 6 ears accompanied by other malformations), the internal auditory canal malformation(8 ears, all accompanied by other malformations). CONCLUSION: MSCT allows a comprehensively assessing various congenital ear malformations through high quality MPR and VRT reconstructions. VRT images can display the site and degree of the malformations three-dimensionally and intuitionisticly. It is very useful to the cochlear implantation.

Immunologic role of nitric oxide in acute rejection of golden hamster to rat liver xenotransplantation.

AIM: To evaluate the immunologic role and expression significances of nitric oxide(NO), nitric oxide synthase(NOS),and its isoenzyme in acute rejection to liver xenografts from golden hamster in rat. METHODS: Liver transplantations were randomly divided into five groups(n=6-9):isografts (group I); xenografts (group II); xenografts plus cyclosporine treatment (group III), xenografts plus cyclophosphamide treatment combined with splenectomy (group IV), and xenografts using cyclophosphamide in combination with splenectomy (group IV) and xenografts using splenectomy in addition to cyclophosphamide and cyclosporine treatments(group V). The levels of ALT,TNF-alpha, and nitric oxide production(NOx) in serum of reciprents were examined,and expressions of type II(iNOS) and type III (cNOS) nitric oxide synthase(NOS)-inducible NOS(iNOS) and constitutive NOS(cNOS) were observed by NADPH diaphorase histochemical and immunohistochemical staining. RESULTS: The level of serum ALT,activity of serum TNF-alpha and systemic levels of NO metabolite in groups II and IV were higher than those of groups I and V(serum ALT,2416+/-475, 2540+/-82.5) nkat.L(-1) vs (556.8+/-43.5, 677.30+/-38.2 ) nkat.L(-1), P<0.01;(serum TNF-alpha, 353.5+/-16.1, 444.6+/-28.1) ng.L(-1), vs 38.5+/-5.2, 52.0+/-5.7) ng.L(-1), P<0.01; (serum NOx 514.6+/-18.1, 336.0+/-43.0)nmol.g(-1), vs 26.1+/-5.7, 27.7+/-6.0)nmol.g(-1), P<0.01. Cyclosporine in group III can repress the cellular immune response and the synthesis of nitric oxide and the expression of NO synthase,but not prolong the liver xenograft survival. The over-expression of NOS,iNOS and cNOS in liver xenograft rejection in groups II and IV were detected by NADPH diaphorase histochemical and immunohistochemical staining. CONCLUSION: The degrees of acute rejection can be effectively repressed in golden hamster to rat liver xenografts with splenectomy and cyclosporine. Nitric oxide metabolites,and nitric oxide synthase and its isoenzymes,above all inducible NOS (iNOS) can be used as potential diagnostic markers for acute rejection in liver transplantation. The cellular localization of nitric oxide varies according to the immunologic status of liver xenografts,thus thinking that hepatocyte derived nitric oxide may be protective in the hyporesponsive state,but hepatic injury is likely triggered by centrilobular iNOS expression in the superresponsive state.