[Protective effect of wenfei huayin recipe on lung of rats with chronic obstructive pulmonary diseases].

OBJECTIVE: To explore the mechanism of Wenfei Huayin Recipe (WHR) in treating chronic obstructive pulmonary diseases (COPD). METHODS: The COPD model was induced by modified fumigating method and intra-tracheal instillation of lipopolysaccharide. Then reformed COPD model of cold-phlegm retention in Fei syndrome type. All the model rats were randomly divided into two groups, the model group and the treated group, treated respectively with WHR and saline for 14 successive days. Besides, a blank group without any intervention was set up for control. The general condition, weight growth rate, pathological changes of lung tissue under light microscope, ultrastructure under electron microscope, arterial blood gas analysis and levels of interleukin 4 (IL-4), interleukin 8 (IL-8), tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) in lung homogenate by radio-immunity assay were observed. RESULTS: In the treated group, as compared with the control group, the symptoms of aversion to cold, swarming, wheezing, the degree of epithelial cell degeneration and necrosis, the inflammatory cell infiltration and the volume of cilia lodging, sloughing, and bullae of lung were lessened and weight growth rate was higher (P<0.01). Moreover, the treated group was superior to the control group in decreasing levels of PaCO2, IL-4, IL-8, TNF-alpha and increasing PaO2, IFN-gamma and IFN-gamma/IL-4 ratio (P<0.01 or P<0.05). CONCLUSION: WHR can correct the Th1/Th2 imbalance and inhibit the inflammatory reaction, displaying an important role in improving the airway function and structure in COPD rats.

Induction of apoptosis by Hax-1 siRNA in melanoma cells.

HS1-associated protein X-1 (Hax-1) is a novel intracellular protein and recent studies suggested that it is an anti-apoptotic factor in different tumors. Hax-1 expression was upregulated in various metastatic tumors and cancer cell lines, including melanoma. To understand the role of Hax-1 in melanoma development and progression, we constructed Hax-1 short interfering RNA (siRNA) expression vectors to downregulate Hax-1 expression in a human melanoma A375 cell line. One of the two Hax-1 RNA interference (RNAi) constructs significantly reduced melanoma cell viability, which was due to induction of apoptosis in A375 cells. Molecularly, the induced apoptosis through downregulation of Hax-1 expression was mediated by activation of caspase-3 and poly-ADP-ribose polymerase (PARP) enzymatic activity in A375 cells. The data indicate that Hax-1 plays a role in suppression of apoptosis and promotion of melanoma cell growth, suggesting that this Hax-1 siRNA has a therapeutic indication in control of melanoma.

Upregulation of Neural Precursor Cell Expressed Developmentally Downregulated 4-1 is Associated with Poor Prognosis and Chemoresistance in Lung Adenocarcinoma.

BACKGROUND: The E3 ubiquitin ligase neural precursor cell expressed developmentally downregulated 4-1 (NEDD4-1) negatively regulates phosphatase and tensin homolog deleted on chromosome 10 (PTEN) protein levels through polyubiquitination and proteolysis, but its significance in lung cancer is still unclear. This study investigated the expression and the role of NEDD4-1 in tumor development and chemosensitivity of lung adenocarcinoma (ADC). METHODS: We retrospectively investigated the expression and significance of NEDD4-1, PTEN, and p-Akt proteins in 135 paired ADC and adjacent noncancerous tissue specimens using immunohistochemistry. Furthermore, we evaluated the relationship between NEDD4-1 expression and clinicopathologic characteristics and prognosis. The effects of small interfering RNA against NEDD4-1 on proliferation and chemosensitivity were examined in A549 cells in vitro using 3- (4,5-dimethylthiazol-2-yl) -5-(3-carboxymethoxyphenyl) -2-(4-sulfophenyl)- 2H-tetrazolium method. The ability of migration and invasion of A549 cells was tested by transwell assay. Moreover, reverse-transcription quantitative polymerase chain reaction and Western blotting analyses were used to determine the expression of NEDD4-1, PTEN, phosphoinositide 3-kinase (PI3K)/Akt activity, and its downstream target proteins. RESULTS: NEDD4-1 protein was significantly upregulated in lung ADC tissues, whereas it was weak or negative in normal lung epithelial cells. The expression of NEDD4-1 in ADC (78.5%, 106/135) was significantly much higher than that in adjacent normal lung tissue (13.3%, 29/135, P < 0.01), and it was associated with lymph node metastasis, tumor-node-metastasis (TNM) stage, and chemotherapy resistance. PTEN expression was downregulated in lung ADC (60.7% vs. 100.0% in noncancerous specimens, P = 0.007), and was negatively correlated with lymph node metastasis, histological variants, clinical stage, chemoresistance. In addition, expression of p-Akt in ADC tissues (71.1% 96/135) was much higher than that in adjacent lung epithelial cells (6.7%, 9/135, P < 0.01). Kaplan-Meier and multivariate analysis demonstrated that expressions of NEDD4-1 and PTEN were both independent risk factors for survival in patients with lung ADC. NEDD4-1 knockdown in vivo decreased proliferation, migration, and invasion and improved chemosensitivity to cisplatin and paclitaxel in A549 cells. NEDD4-1 knockdown also significantly enhanced PTEN expression and inhibited p-Akt activity and downstream target proteins. CONCLUSIONS: NEDD4-1 upregulation may contribute to the progression of lung ADC. NEDD4-1 may regulate the proliferation, invasion, migration, and chemoresistance of lung ADC cells through the PI3K/Akt pathway, suggesting that it may be regarded as a therapeutic target for the treatment of lung ADC.

[Effects of drug cupping therapy on immune function in chronic asthmatic bronchitis patients during protracted period].

UNLABELLED: To observe the clinical effect of drug cupping therapy (DCT, cupping therapy with pingchuan ointment made by the authors themselves in the cups) on chronic asthmatic bronchitis (CAB) during the protracted period, and explore its effect on immune function. METHODS: Seventy-seven patients were randomly divided into two groups:the treated group (n=40) treated by orally taken Liuwei Dihuang Pill (LDP) and DCT and the control group (n=37) with LDP and common cupping therapy without drug in cups. The changes of T-lymphocyte subset, levels of interferon-gamma (IFN-gamma), interleukin (IL), immunoglobulin (Ig), complement 3 and 4 (C3 and C4) were detected before and after treatment. RESULTS: The total effective rate was higher in the treated group than that in the control group (90.0% vs. 59.5%, P < 0.01). The levels of CD4+, CD4+ /CD8+, IL-2, IFN-gamma, C3, C4, IgA, IgG and IgM increased, while the levels of IgE, IL-4, IL-10 and CD8+ decreased after treatment in both groups (P < 0.05 or P < 0.01), the improvements were better in the treated group than that in the control group (P < 0.05). CONCLUSION: DCT shows better curative effects than that of common cupping therapy without drug, it could improve the cellular and humoral immunity in CAB patients.

Primary extragastrointestinal stromal tumor of the pleura: A case report.

Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal tumor of the gastrointestinal tract. The stomach and small intestine are the most common sites of occurrence. GISTs are mesenchymal neoplasms originating from the interstitial cells of Cajal (ICCs), and are characterized by positivity for cluster of differentiation (CD) 117, also known as proto-oncogene c-Kit. While the majority of GISTs develop in the alimentary tract, in rare cases they may also be found in extragastrointestinal tissues. This type of GIST is known as an extragastrointestinal stromal tumor (EGIST). Despite the fact that EGISTs have been reported in the mesentery, omentum and retroperitoneum, primary intrathoracic EGISTs, arising from the pleura or lungs, are rare. The patient presented in the current study was a 40-year-old man, who presented with a cough and pyrexia, with pleural effusion on the left side. Multiple nodules throughout the parietal pleura were identified by thoracoscopy and a diagnosis of primary GIST of pleura was established, since they were positive for CD117 and discovered on GIST-1 and there was no evidence of gastrointestinal tumors. Subsequently, the patient was administered with imatinib and had no signs of disease recurrence 2 years later.

Alterations of pulmonary function in patients with inflammatory bowel diseases.

AIM: The aim of this study was to investigate the alterations of pulmonary function tests (PFTs) and their relationship with disease activity in inflammatory bowel diseases (IBDs). METHODS: Sixty-four IBD patients (31 Crohn's disease [CD] and 33 ulcerative colitis [UC]) and thirty healthy individuals (controls) were studied with regard to the following parameters of PFTs: Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), their ratio, mid-forced expiratory flow of 25-75% (FEF 25-75), residual volume, total lung capacity, and diffusing capacity of the lung for carbon monoxide (DLCO). The disease activity was calculated using the Crohn's Disease Activity Index for CD and Mayo Clinic Score for UC. Correlation analysis was performed between disease activity and sputum cytology and PFTs. RESULTS: Nineteen of the 31 CD patients (61.29%) and 17 of the 33 UC patients (51.52%) but none of the controls showed at least one abnormal PFTs (P < 0.05). Compared with controls, both CD and UC patients exhibited a significant reduction in FEV1 (P < 0.05), FVC (P < 0.05), FEF 25-75 (P < 0.05), and DLCO (P < 0.05). The majority with decreased measurements of PFTs were in the active phase of diseases (P < 0.05). IBD activity scores correlated negatively with some parameters of PFTs and positively with lymphocytosis and eosinophilia of sputum (P < 0.05). CONCLUSIONS: Pulmonary function disorders are significantly common in IBD patients. The impairment in active disease is significantly greater than in remission.

Effect of ambroxol on the concentration of cefotaxime in the bronchoalveolar lavage fluid of rats with pulmonary fibrosis.

This study aimed to investigate the effect of ambroxol on the concentration of cefotaxime in the bronchioalveolar lavage fluid of rats with bleomycin-induced pulmonary fibrosis. A total of 54 Wistar male rats were randomly divided into three groups, namely the normal control group, model group and ambroxol group. On experimental day 0, the rats were intratracheally instilled with bleomycin (5 mg/kg body weight) or sterile saline. The rats in the ambroxol group were then treated with ambroxol (35 mg/kg/day) intraperitoneally. On days 7, 14, 28 after instillation, six rats from each group were sacrificed, bronchial alveolar fluids were recovered and the lungs were collected for histopathological examination following the injection of cefotaxime (600 mg/kg) intravenously. The concentration of cefotaxime in the bronchial alveolar fluids was assayed by a liquid chromatography-mass spectrometry method. On day 7, the concentration of cefotaxime in the bronchial alveolar fluid of the ambroxol group was lower than that of the model group. On day 14, the concentration of cefotaxime in the bronchial alveolar fluids of the ambroxol group was higher than that of the model group, and the difference between these groups was significant statistically (P<0.001). On day 28, the concentration of cefotaxime in the bronchial alveolar fluids of the ambroxol group decreased sharply, and was lower than that of the model group (P=0.126). These results indicate that ambroxol increased the concentration of cefotaxime in the bronchial alveolar fluids at the primary fibrosis stage.

[Clinical study on treatment of liver fibrosis in patients of hepatitis B by kangxian baogan decoction].

OBJECTIVE: To explore the clinical effect and therapeutic mechanism of Kangxian Baogan Decoction (KXBGD) on liver fibrosis caused by chronic hepatitis B. METHODS: Eight-one patients with chronic hepatitis B were divided into two groups randomly. The 54 patients in the treated group were treated by KXBGD and the 27 patients in the control group were treated by conventional liver protecting treatment. Serum levels of hyaluronic acid (HA), procollagen type III (PC III), collagen type IV (C-IV), laminin (LN), transforming growth factor beta 1 (TGF beta 1) and tumor necrosis factor-alpha (TNF-alpha) were measured before and after treatment, meanwhile, liver function and pathological changes of liver tissues were observed. RESULTS: The total effective rate in the treated group was significantly higher than that in the control group. Serum levels of HA, PC III, C-IV, LN, TGF beta 1 and TNF-alpha in the treated group obviously reduced after treatment, and the liver function got better with significant difference as compared with those in the control group (P < 0.05 or P < 0.01). Pathological examination of liver biopsy showed that the fibrous tissue in the liver reduced. CONCLUSION: KXBGD has a definite effect of anti-liver fibrosis.

[Effect of tongxinluo capsule on plasma endothelin and calcitonin gene related peptide in patients with unstable angina pectoris].

OBJECTIVE: To investigate the effect of Tongxinluo capsule (TXLC) on the patients with unstable angina pectoris (UAP). METHODS: Patients of UAP were divided into two groups, the treated group (n = 60) was treated with TXLC and the Danshen group (n = 30) was treated with composite Danshen tablet. The plasma endothelin (ET) and calcitonin gene related peptide (CGRP) were measured before and after treatment. Data were compared between the two groups and also compared with those measured in 20 healthy subjects for control. RESULTS: ET level was higher and CGRP level lower significantly in UAP patients than that in healthy subjects significantly (P < 0.05). After TXLC treatment, ET significantly lowered (P < 0.01) and CGRP increased (P < 0.05). But in the Danshen group after treatment, the former decreased (P < 0.05), while the latter remained unchanged (P > 0.05). The effect of TXLC was better than that of composite Danshen tablet. CONCLUSION: TXLC is an effective drug for UAP treatment, which could efficiently regulate the ET and CGRP metabolism and ameliorate the degree of myocardial ischemia damage.

[The relationship between transforming growth factor-beta1, platelet derived growth factor and airway remodeling in eosinophilic bronchitis].

OBJECTIVE: To study the relationship between the expression of transforming growth factor-beta(1) (TGF-beta(1)) and platelet derived growth factor (PDGF) and airway remodeling in eosinophilic bronchitis (EB). METHODS: Bronchial biopsy specimens were obtained from 12 patients with EB (A group), 10 asthmatic patients (B group) and 10 patients (C group) with peripheral lung cancer in early stage. The subepithelial basement membrane (SBM) thickness was measured by light microscopy using HE staining. The expressions of TGF-beta(1) and PDGF in the bronchial mucosa were examined by immunostaining. RESULTS: The SBM of A group [(6.3 +/- 1.4) micro m] was significantly thicker than that of C group [(4.1 +/- 1.2) micro m, P < 0.05], but significantly thinner than that of B group [(8.2 +/- 1.5) micro m]. The numbers of positive cells for TGF-beta(1) and PDGF in A group (59 +/- 9, 47 +/- 7 respectively) and B group (85 +/- 12, 76 +/- 11, respectively) were significantly higher than those in C group (31 +/- 4, 20 +/- 3, respectively), and were positively correlated with SBM thickness (r = 0.76, 0.52, P < 0.05). CONCLUSION: These results suggest that TGF-beta(1) and PDGF expressions in bronchial mucosa may play a role in bronchial subepithelial fibrosis in EB patients.

Pulmonary manifestations of Crohn's disease.

Crohn's disease (CD) is a systemic illness with a constellation of extraintestinal manifestations affecting various organs. Of these extraintestinal manifestations of CD, those involving the lung are relatively rare. However, there is a wide array of lung manifestations, ranging from subclinical alterations, airway diseases and lung parenchymal diseases to pleural diseases and drug-related diseases. The most frequent manifestation is bronchial inflammation and suppuration with or without bronchiectasis. Bronchoalveolar lavage findings show an increased percentage of neutrophils. Drug-related pulmonary abnormalities include disorders which are directly induced by sulfasalazine, mesalamine and methotrexate, and opportunistic lung infections due to immunosuppressive treatment. In most patients, the development of pulmonary disease parallels that of intestinal disease activity. Although infrequent, clinicians dealing with CD must be aware of these, sometimes life-threatening, conditions to avoid further impairment of health status and to alleviate patient symptoms by prompt recognition and treatment. The treatment of CD-related respiratory disorders depends on the specific pattern of involvement, and in most patients, steroids are required in the initial management.

[Efficacy observation on acupuncture and moxibustion combined with hot compress of TCM herbs for scleroderma].

OBJECTIVE: To assess the clinical efficacy and safety of surrounding needle, moxibustion and hot compress of TCM herbs for localized scleroderma. METHODS: Forty-two cases of localized scleroderma were randomly divided into an acupuncture + herb group (23 cases, group A) and a heparin sodium group (19 cases, group B). Both the two groups were orally administrated with centella triterpenes tablets and vitamin E, group A was additionally treated with surrounding needle at local area, moxibustion at affected site and Hegu (LI 4), Zu sanli (ST 36) as well as hot external application of "hot compress herbs" at local location, while group B was treated with external application of heparin sodium cream. Both the two groups were treated for consecutive 6 months, and scores of skin sclerosis, joint pain and function were compared before and after the treatment. Also the efficacy and safety of TCM syndrome were assessed. RESULTS: Compared with that before the treatment, the scores of skin sclerosis, joint pain and joint function in the group A after treatment were significantly decreased (all P < 0.01), the score of skin sclerosis in the group B was improved (P < 0.05), and the three types of score in the group A was obviously lower than those in the group B (both P < 0.05). The total effective rate was 86.4% (19/22) in the group A, which was superior to 52.6% (10/19) in the group B (P < 0.05). CONCLUSION: The surrounding needle, moxibustion and external application of "hot compress herbs" could improve skin sclerosis in patients with localized scleroderma, which has obvious efficacy and relative safety.

Tracheobronchial nodules and pulmonary infiltrates in a patient with Crohn's disease.

Crohn's disease is a granulomatous systemic disorder of unknown etiology. Obvious pulmonary involvement is exceptional. Tracheal involvement in Crohn's disease is even more unusual, only a few cases have been reported to date. We herein report a rare case of tracheobronchial nodules and pulmonary infiltrates in both lungs as a complication of Crohn's disease. A 42-year-old man underwent pancolectomy for multiple broken colon caused by Crohn's disease. Forty days later pulmonary symptoms and radiologic abnormalities were noted. A search for bacterial (including mycobacteria) and fungal in the repeated sputum proved negative. The treatment consisted of intravenous antimicrobials for one month, but there was no improvement in pyrexia or cough and radiologic abnormalities. Fibreoptic bronchoscopy (FOB) was performed and revealed nodes in the trachea and the right upper lobe opening. Histopathology of tracheobronchial nodules and bronchial mucosa biopsy specimen both showed granulomatous inflammation with proliferation of capillaries and inflammatory cells. Oral steroid and salicylazosulfapyridine were commenced and led to marked improvement in symptoms and an almost complete resolution of his chest radiograph. Repeated FOB showed that nodes in the trachea disappeared and the ones in the right upper lobe opening diminished obviously. Crohn's disease can be associated with several respiratory manifestations. The form of tracheal and bronchopulmonary involvement in Crohn's disease is rare and responded well to steroids.

[Roles of Th17 lymphocytes and inflammatory cytokines in airway inflammation exacerbation of murine asthmatic model].

AIM: To investigate the roles of Th17 lymphocytes and its inflammatory cytokines in airway inflammation exacerbation of murine asthmatic model. METHODS: Twenty mice were randomized into control group and asthma group. For the murine asthma model, the mice were sensitized and challenged with ovalbumin (OVA). The control mice were given normal saline alone under the same conditions as the asthma group. We observed the changes in cellular proportions in the bronchoalveolar lavage fluid (BALF) under a light microscope and the histological changes in lung tissue by HE staining. The levels of IL-4, IFN-γ and IL-17 were detected by ELISA. Th1, Th2 and Th17 cells in the peripheral blood were detected by flow cytometry. We did a correlation analysis between Th1, Th2 and Th17 cells in the peripheral blood and neutrophils in BALF. RESULTS: The total cell number and the percentages of neutrophils, eosinophils and lymphocytes in BALF of the asthmatic mice were significantly higher than those in the control mice (P<0.05). The neutrophils and eosinophils infiltration in pulmonary tissue was also dramatically detected in asthmatic mice. The levels of IL-4 and IL-17 were significantly higher than those in the control mice (P<0.05), while the level of IFN-γ was much lower than in the control mice (P<0.05). Besides, the percentages of Th2 and Th17 cells in peripheral blood were significantly higher in the asthmatic mice than in the control mice (P<0.05). The expression of Th17 was positively correlated with the levels of neutrophils in BALF(r(Th17);=0.394, P<0.05), and the expression of Th1 was negatively correlated with the level of neutrophils in BALF (r(Th1);=-0.446, P<0.05). CONCLUSION: Th17 cells could induce the recruitment of inflammatory cytokines and neutrophils into airways, which might aggravate the asthmatic inflammation and be related with asthma exacerbation.

[Effects of Hax-1 siRNA on sensitivity to chemotherapy of melanoma A375 cells].

AIM: To investigate the effects of Hax-1 siRNA on sensitivity to chemotherapy of melanoma A375 cells. METHODS: The effects of Hax-1 siRNA combined with cisplatin(DDP) or Matrine(Mat) on proliferation, apoptosis of A375 cells and active forms of caspase-3 were detected with MTT assay, Annexin V-FITC/PI staining with FCM, Hoechst 33258 staining, and Western blot respectively. RESULTS: The inhibition of proliferation , induction of apoptosis and the expression of active caspase-3 forms in DDP or Mat treated A375 cells transfected with Hax-1 siRNA were all significantly higher than those in untransfected A375 cells or A375 cells transfected with control siRNA (P<0.05). The distinctive apoptotic morphology was observed in Mat or DDP treated A375 cells transfected with Hax-1 siRNA. CONCLUSION: The data from our current study indicate that Hax-1 siRNA could enhance the effects of DDP or Mat on inhibition of melanoma A375 cell growth and induction apoptosis, which may be caused by the increased expression of active forms of caspase-3.