AZGP1 suppresses epithelial-to-mesenchymal transition and hepatic carcinogenesis by blocking TGFß1-ERK2 pathways.

Zinc-α2-glycoprotein 1 (AZGP1) has been found to play important roles in TGF-ß1 induced epithelial-to-mesenchymal transition (EMT). However, the mechanisms of AZGP1 inhibiting EMT and its therapeutic potential remain unknown in hepatocellular carcinoma (HCC). AZGP1, TGF-ß1 or ERK2 expressions were examined in liver tissues of HCC patients and rat model. The effect of AZGP1 on EMT and crosstalking of TGFß1-ERK2 signaling in human hepatic cancer cell was tested in vitro and in vivo. Hepatic expression of AZGP1 was nearly deficient in HCC patients and rats. It was proved that AZGP1 has the ability of down-regulating mesenchymal markers, up-regulating epithelial marker, inhibiting cell invasion and suppressing EMT in human HCC cells. The results clarified that AZGP1 has the effect on blocking TGF-ß1 mediated ERK2 phosphorylation leading to depressing EMT and invasive potential in vitro. Local injection of AZGP1 mimic in vivo could significantly withhold lung metastasis in HCC. In conclusion, loss of AZGP1 could trigger EMT induced by TGFß1-ERK2 signaling, confuse in energy metabolism, reduce cell proliferation and apoptosis, activate survival signals and promote invasion. Up-regulation of AZGP1 should be proposed to reverse EMT and might be a new promising therapy for HCC.

FOXP1 and SPINK1 reflect the risk of cirrhosis progression to HCC with HBV infection.

BACKGROUND: Hepatocellular carcinoma (HCC) deriving from cirrhosis with HBV infection harbors higher morbidity and poor prognosis. The diagnosis of HCC at its early stage is essential for improving the effect of treatment and survival rate of patients. METHOD: Affymetrix GeneChip was practiced to establish gene expression profile and significance analysis of microarray (SAM) as well as prediction analysis of microarray (PAM) was utilized to screen candidate marker genes in tissue of carcinoma and para-cancerous with cirrhosis from 15 hepatitis B virus (HBV) related HCC patients. RESULT: Total 497 differential genes were selected by microarray (fold change >2; P value<0.01). Then 162 significant genes were determined by SAM (fold change -1.46 to 1.28). A number of 8-genes showing "poor risk signature" was validated with threshold of 6.2, which was associated with cirrhosis progressing to HCC. Only 3 down-regulated and 2 up-regulated predictor genes had statistical difference in HCC and cirrhosis groups by RT-PCR (P value<0.01). Forkhead box protein 1 (FOXP1) and serine protease inhibitor Kazal-type 1 (SPINK1) proteins were found significantly increased in carcinoma tissues than para-cancerous cirrhotic tissues by IH and WB. CONCLUSION: Over-expression of FOXP1 and SPINK1 may participate in the carcinogenesis of HBV related cirrhosis. They could use as potential biomarkers for diagnosing early HCC.

Expression of serum cytokines in patients with pneumoconiosis by antibody chip / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the changes in expression of serum cytokines in patients with pneumoconiosis using cytokine antibody chips (CACs).</p><p><b>METHODS</b>The CAC technology was applied to measure the serum levels of 60 cytokines in 12 patients with pneumoconiosis and 3 normal controls.</p><p><b>RESULTS</b>In the patients with pneumoconiosis, the highly expressed serum cytokines included interleukin (IL)-1α, IL-1β, IL-2, ILs 4-16, macrophage colony-stimulating factor, interferon-γ, tumor necrosis factor (TNF)-α, TNF-β, human bone morphogenetic protein-6, fibroblast growth factor-7, neurotrophin-3, and stem cell factor, and the lowly expressed serum cytokines included recombinant human I-309, monocyte chemoattractant protein (MCP)-1, MCP-2, MCP-3, MCP-4, macrophage inflammatory protein (MIP)-1-δ, and MIP-3-α.</p><p><b>CONCLUSION</b>Patients with pneumoconiosis have changes in the expression of most serum cytokines.</p>

Value of bacteria culture and antimicrobial susceptibility test of bronchoalveolar lavage fluid in diagnosis and treatment of refractory pneumonia in children / 中华实用儿科临床杂志

Objective To evaluate the value of bacteria culture and antimicrobial susceptibility test of bronchoalveolar lavage fluid(BALF) in diagnosis and treatment of refractory pneumonia in children.Methods Three hundred and sixty-eight patients who failed to a 2 weeks,routine antibiotic therapy,hospitalized in Department of Respiration,Tianjin Children's Hospital from Aug.2010 to Dec.2011,were diagnosed as refractory pneumonia.They were examined with fiberoptic bronchoscopy,BALF was collected,and bacteria culture and antimicrobial susceptibility test in BALF were performed.Results One hundred and ninety-five stains of bacteria were identified from BALF of 181 cases.There were 10 (5.1％) gram-positive stains (7 Streptococcus pneumonia and 3 Staphylococcus aureus),48 stains (24.6％) were gram-negative bacterial,and the predominant were Pseudomonas aeruginosa (23 stains,11.8 ％),followed by Serratia marcescens and Stenotrophomonas maltophilia (6 stains respectively,3.1％).There were 1 Staphylococcus aureus with positive beta-lactamases and 1 Pseudomonas fluorescens with positive AmpC enzyme.There were 1 fungi (0.5％)and 136 parasitic bacteria stains(69.7％).Gram-positive stains were universally resistant to Erythromycin,Penicillin,Cefuroxime,and susceptible to Chloramphenicol,Levofloxacin,Vancomycin.Gram-negative stains were universally resistant to Ampicillin,Cefazolin,Cefuroxime,Cefotaxime,and susceptible to Amikacin,Cefepime,Cefoperazone sulbactam,Meropenem,Imipenem,Levofloxacin,Ceftazidime,Piperacillin.There were mixed infection in most children and the predominant pathogen was Mycoplasma pneumoniae.Conclusions Bacteria culture of BALF is relatively reliable and instructively recommended for the treatment of refractory pneumonia in children,meanwhile,it can help choose the antibiotics reasonably.

Application of auditory brainstem response (ABR) and 40 Hz auditory event related potential (40 Hz AERP) to the diagnosis of occupational noise-induced hearing impairment / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the application of auditory brainstem response (ABR) and 40 Hz auditory event related potential (40 Hz AERP) to the diagnosis of occupational noise-induced hearing impairment and to provide the evidence for diagnosis of occupational deafness.</p><p><b>METHODS</b>Pure tone audiometry, ABR and 40 Hz AERP were performed in 54 workers occupationally exposed to noise. The thresholds of higher frequency band, 3 kHz and 4 kHz were compared with the threshold of ABR. The thresholds of auditory frequency ban and 0.5 kHz were compared with the threshold of 40 Hz AERP.</p><p><b>RESULTS</b>A better correlation was found between thresholds of ABR and higher frequency pure tone audiometry. There was a significant difference of thresholds between 40 kHz AERP and pure tone audiometry. The correction values of thresholds between 40 kHz AERP and pure tone audiometry in the light noise-induced hearing impairment group and the moderate noise-induced hearing impairment group were (16.43 ± 1.08) and (11.80 ± 1.12) dBn HL, respectively.</p><p><b>CONCLUSION</b>In diagnosis of occupational noise-induced hearing impairment, the threshold of ABR can be used to estimate the hearing threshold of pure noise higher frequency. Because there is the significant difference of the thresholds between pure tone audiometry and 40 Hz AERP, the response threshold can not be served as the audiometry threshold, and the behavioral hearing thresholds can only be obtained by adjusting the response threshold with respective correction value.</p>

[Umbilical cord mesenchymal stem cell transplantation for treatment of experimental autoimmune myasthenia gravis in rats].

Umbilical cord mesenchymal stem cell (UCMSC) transplantation has been widely used in the treatment of a variety of diseases due to their advantages such as abundant resources, low immunogenicity and large ex vivo expansion capacity. This study was aimed to investigate the effects of UCMSC on experimental autoimmune myasthenia gravis (EAMG) rats. The distribution of human-derived cells was observed by immunofluorescence method, the effect of MSC on B-cell in situ-secreted antibodies was assayed by ELISPOT, the secreted IFN-γ level was detected by using Transwell test. The results showed that UCMSC were able to migrate to inflammation region and lymph nudes, moreover human-derived cells could be detected in medulla zone of lymph nudes. In vitro in situ detection of AchR specific antibody secretion revealed that the full contact of MSC with lymphnode-derived lymphocytes could effectively inhibit production of AchR antibody. Transwell test indicated that the direct contact of UCMSC with CD4 T cells could effectively decrease production of IFN-γ, which modulated the unbalance between Th1/Th2 to a certain extent. It is concluded that UCMSC can regulate the immune system by direct cell-cell contact or/and release of cytokines, which bring a new insight into knowledge about MSC-based therapy for EAMG.

Evaluation of different oxygen therapies on therapeutic effects in rats with acute carbon dioxide poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study therapeutic effects by using different oxygen therapies in rats with acute carbon dioxide poisoning, to select the best oxygen therapy technology for patients with acute carbon dioxide poisoning on the spot.</p><p><b>METHODS</b>Sixty healthy male Sprague-Dawley rats were randomized into normal control group, carbon dioxide exposure group, hyperbaric oxygen treatment group (pressure 2 ATA, FiO(2)100%), high concentration of atmospheric oxygen treatment group (FiO(2)50%), low concentration of atmospheric oxygen treatment group (FiO(2)33%). After treated with different oxygen in rats with acute carbon dioxide poisoning, arterial pH, PO2 and PCO2 of rats were detected, in addition observe pathological changes of lung tissue and brain tissue.</p><p><b>RESULTS</b>The arterial pH (7.31 ± 0.06) and PO2 [(68.50 ± 15.02) mm Hg] of carbon dioxide exposure group were lower than those of control group [pH (7.42 ± 0.02) and PO2 (92.83 ± 8.27) mm Hg], PCO2 [(71.66 ± 12.10) mm Hg] was higher than that of control group [(48.25 ± 2.59) mm Hg] (P < 0.05); the arterial pH (hyperbaric oxygen treatment group 7.37 ± 0.02, high concentration of atmospheric oxygen treatment group 7.39 ± 0.03, low concentration of atmospheric oxygen treatment group 7.38 ± 0.02) and PO2 of oxygen treatment groups [hyperbaric oxygen treatment group, high concentration of atmospheric oxygen treatment group, low concentration of atmospheric oxygen treatment group were (82.25 ± 12.98), (84.75 ± 11.24), (83.75 ± 16.77) mm Hg, respectively] were higher than that of carbon dioxide exposure group, PCO2 [hyperbaric oxygen treatment group, high concentration of atmospheric oxygen treatment group, low concentration of atmospheric oxygen treatment group were (52.25 ± 4.95), (51.75 ± 4.82), (52.66 ± 5.61) mm Hg, respectively] was lower than that of carbon dioxide exposure group (P < 0.05); there was no significant difference of the arterial pH, PO2 and PCO2 between oxygen treatment groups and control group (P > 0.05); there was no significant difference of the arterial pH, PO2 and PCO2 among oxygen treatment groups (P > 0.05). There was large area of bleeding of lungs in rats with carbon dioxide poisoning, the bleeding of lungs in rats with high concentration of atmospheric oxygen treatment and low concentration of atmospheric oxygen treatment was better than the rats with carbon dioxide poisoning, there was no abnormal appearance of lungs in rats with hyperbaric oxygen treatment. The light microscope observation showed that there were diffuse bleeding and exudation of lungs in rats with carbon dioxide poisoning, the bleeding and exudation of lungs in rats with high concentration of atmospheric oxygen treatment and low concentration of atmospheric oxygen treatment were better than the rats with carbon dioxide poisoning, there were only minor bleeding and exudation of lungs in rats with hyperbaric oxygen treatment. There was no difference of brain in anatomy and microscopy among all groups, there were no significant bleeding, edema, cell degeneration and necrosis.</p><p><b>CONCLUSIONS</b>Lung pathology in acute carbon dioxide poisoning rats with hyperbaric oxygen treatment is better than the rats with high concentration of atmospheric oxygen treatment and low concentration of atmospheric oxygen treatment, there is no significant difference of effect between high concentration of atmospheric oxygen treatment group and low concentration of atmospheric oxygen treatment group, however, the results of blood gas analysis and lung pathology than the exposure group improved, so qualified medical unit for hyperbaric oxygen therapy as soon as possible, hyperbaric oxygen treatment facilities in the absence of circumstances, the emergency treatment of early oxygen is also a good measure.</p>

Evaluating the effects of different oxygen therapies on the rats with acute nitrogen asphyxia / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To Evaluate the effects of different oxygen therapies on the rats with acute nitrogen asphyxia and to study the best oxygen therapic protocol for patients with acute nitrogen asphyxia on the spot.</p><p><b>METHODS</b>Sixty healthy male Wistar rats were divided into 5 groups: control, exposure to nitrogen, 33% oxygen treatment, 50% oxygen treatment and hyperbaric oxygen treatment groups. The behavioral performance, arterial oxygen pressure (PO2), carbon dioxide partial pressure (PCO2) and oxygen saturation (SPO2), biochemical changes in liver and kidney function and myocardial enzymes in 5 groups were measured.</p><p><b>RESULTS</b>The rats exposed to nitrogen firstly were excited then inactive symptoms, but consciousness was recovered after oxygen therapy. The PO2 and SPO2 in nitrogen exposure group were (79.67 +/- 9.12) and (94.92 +/- 2.78) mm Hg, respectively, which were significantly lower than those in control group (P<0.01). The PO2 and SPO2 of 3 oxygen treatment groups were (94.75 +/- 7.24), (94.92 +/- 8.98), (104.58 +/- 7.12)mm Hg and (97.17 +/- 0.83), (96.92 +/- 1.16), (97.42 +/- 0.67)mm Hg, respectively, which were significantly higher than those in nitrogen exposure group (P<0.05). The PO2 in hyperbaric oxygen treatment group was significantly higher than those in other 2 oxygen treatment groups (P<0.05). The SPO2 in hyperbaric oxygen treatment group was (51.42 +/- 6.60) mm Hg which was significantly higher than that [(44.58 +/- 3.42)mm Hg] in 50% oxygen treatment groups (P< 0.05). AST [(270.50 +/- 49.05 )U/L], ALT [(122.67 +/- 55.44 )U/L], BUN [(7.31 +/- 0.93 )mmol/L], Cr[(28.32 +/- 4.35) micromol/L], CK [(1808.42 +/- 582.05)U/L] and CtnI [(22.52 +/- 14.29 )ng/ml] in nitrogen exposure group were significantly higher than those in control group (P<0.05). AST [(165.25 +/- 30.87) U/L], HBDH [(350.83 +/- 103.00)U/L] and CtnI [(11.23 +/- 5.38) ng/ml] in hyperbaric oxygen treatment group were significantly lower than those in other 2 oxygen treatment groups (P<0.05).</p><p><b>CONCLUSION</b>Timely and effective oxygen therapy can significantly increase arterial pressure of oxygen and oxygen saturation in the rats with acute nitrogen asphyxia, and can improve liver function and cardiac damage. The hyperbaric oxygen chamber can significantly increase the therapeutic effects on rats with acute nitrogen asphyxiation.</p>

Clinical study on pneumoconiosis with pulmonary thromboembolism / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To probe into the clinical features and the rescue of pneumoconiosis with pulmonary thromboembolism (PTE).</p><p><b>METHODS</b>26 patients with pneumoconiosis and PTE, male 16, female 10, were collected from June 2002 to June 2006 and 42 patients only with pneumoconiosis served as control. Tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), thrombomodulin (TM), plasma protein S, C (Ps, Pc), homocysteine (Hcy) were measured by the methods of ILISA, and antithrombin (AT-III) by chromo substrate method before and after the treatment of heparin.</p><p><b>RESULTS</b>The average age of patients with pneumoconiosis and PTE was 66.0 +/- 11.9 years old. The number of patients with pneumoconiosis of degree 1, 2, 3 was 3, 16 and 7 respectively. After anticoagulant therapy of heparin, 23 were well improved, and 3 died of acute respiratory failure. Dyspnea, chest pain, hemoptysis, syncope were the conspicuous symptoms. The levels of D-Dimer (0.63 +/- 0.14 mg/L), TM (5.02 +/- 1.24 microg/L) were significantly higher than those of the control (P < 0.05), and significantly lower again after the treatment (P < 0.05). The level of AT-III (96.68 +/- 7.23%) was significantly lower than that of the control, and higher again after the treatment (P < 0.05).</p><p><b>CONCLUSION</b>PTE is often developed in the elder patients with high degree of pneumoconiosis (> or = 2 degree). Clinical features are complicated and non-specific, with the high negative ratio of D-Dimer (7/26), high mortality and high complications of anticoagulant therapy.</p>