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@#Objective - To investigate the effect of lung flora dysbiosis on the process of pulmonary fibrosis and lung epithelial （ ） Methods - mesenchymal transition EMT in mice with silicosis. Male C57BL/6 mice of specific pathogen free grade were ， ， ， （ ） randomly divided into the blank control group silicosis model group solvent control group vancomycin VM + ampicillin （ ） ， （ ） （ ） ， AMP group metronidazole MNZ + neomycin NEO group and mixed treatment group 12 mice in each group. Except for ， ， the blank control group which was given 20.0 µL of 0.9% NaCl solution the other five groups of mice were dosed with 20.0 µL of silica dust suspension at a mass concentration of 250.0 g/L using a single tracheal drip to establish the silicosis mouse model. ： The intranasal drip method was used to treat silicosis mice in each group as following mice in the solvent control group were - ； ； given double distilled water mice in the VM+AMP group were given VM at a mass concentration of 0.5 g/L and AMP at 1.0 g/L ； mice in the MNZ+NEO group were given MNZ at a mass concentration of 1.0 g/L and NEO at 1.0 g/L mice in the mixed ， treatment group were given the same doses of the four antibiotics mentioned above all in a drip volume of 50.0 µL. Silicosis ， ， mice were treated seven days and half an hour before silica dusting and 7 14 and 21 days after silica dusting. Mouse lungtissue was collected aseptically 28 days after silica dusting. Hematoxylin eosin and Masson trichrome staining methods were - used to observe the pathological changes. Western blotting was used to detect the relative protein expression of α smooth muscle （ - ）， - （ - ） （ ） actin α SMA E cadherin E CAD and vimentin VIM . Immunohistochemistry was used to detect the relative expression of - - E CAD and VIM. Real time fluorescence quantitative polymerase chain reaction was used to detect the expression levels of （Col1a2） Results collagen type Ⅰ alpha 2 mRNA in lung tissues. The histopathological results showed that the alveoli of the ， blank control group were thin and structurally intact with few surrounding infiltrating inflammatory cells and no abnormal ， distribution of collagen fibers. The alveoli of the silicosis model group were structurally disorganized with a large number of ， ， infiltrating inflammatory cells thickened alveolar walls and cellular fibrous nodules with abundant blue collagen deposit. In the ， ， VM+AMP group MNZ+NEO group and the mixed treatment group the inflammation and fibrosis were reduced with diferent degrees in the lung tissues compared to the silicosis model group and the solvent control group. The relative expression levels of - ， Col1a2 α SMA VIM protein and mRNA in lung tissues of mice in the silicosis model group were higher than those in the blank （ P ）， -CAD control group all <0.05 and the relative expression levels of E protein were lower than those in the blank control （P ） - ， Col1a2 group <0.05 . The relative expression levels of α SMA VIM protein and mRNA in lung tissues of mice in the MNZ+ （ P ）， -CAD NEO group and the mixed treatment group were lower all <0.05 and the relative expression levels of E protein were （P ）， Conclusion higher <0.05 when compared with the silicosis model group and the solvent control group. Pulmonary fibrosis ， - was reduced in silicosis mice with interventions in lung flora where anaerobic and gram negative bacteria affected pulmonary fibrosis and dysbiosis of the lung flora affected pulmonary EMT.
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Abstract This study investigated the protective effect of dexmedetomidine (Dex) on lung injury during one-lung ventilation (OLV) in elderly patients undergoing radical esophagectomy with remote ischemic preconditioning (RIPC). Fifty-four esophageal cancer patients undergoing radical esophagectomy were divided into control, RIPC and RIPC+Dex group. During the anesthesia and ventilation in surgery, the RIPC was performed in RIPC group, and the intravenous infusion of Dex based on RIPC was conducted in RIPC+Dex group. At the time immediately before OLV beginning (T1), 60 min of OLV (T2) and end of surgery (T3), the oxygenation index (OI) and respiratory index (RI) were recorded, and the serum superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) levels were determined. Results showed that, compared with RIPC group, in RIPC+Dex group the OI at T2 and T3 increased, the RI at T2 and T3 decreased, the serum SOD level at T3 increased, the serum MDA level at T3 decreased, the serum TNF-α and IL-6 levels at T2 and T3 decreased (all P < 0.05). In conclusion, for elderly patients undergoing radical esophagectomy with RIPC, Dex can effectively inhibit the oxidative stress and inflammatory response during OLV, thus alleviating the lung injury and reducing the postoperative complications.
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@#[Abstract] Objective: To explore the clinical significance and in vitro biological effect of ubiquitin carboxyl-terminal hydrolase L5 (UCHL5) expression in thyroid carcinoma (TC) tissues. Methods: TCGAdata were used to analyze the expression of UCHL5 in thyroid carcinoma tissues and its relationship with the prognosis of patients. 82 pairs of TC tissues and corresponding adjacent tissues were collected in the Department of Vascular and Thyroid Surgery, Sichuan Provincial People's Hospital from May 2018 to July 2019; TC cell lines (KTC-1 and WRO) were cultured in vitro, and transfected with UCHL5 overexpression vectors or their control vectors via lentivirus. The mRNAand protein expressions of UCHL5 and B-Raf proto-oncogene serine/threonine-protein kinase (BRAF) in tissues and cells were detected by qPCR and Western blotting, respectively. Cell proliferation was detected by CCK-8, and cell invasion and migration were detected by Transwell and Wound-healing experiments. Results: The expression of UCHL5 was low in TC tissues (P<0.01), and its expression was upregulated in tumor tissues with high TNM stage (P<0.01). The expression of UCHL5 was significantly correlated with BRAF expression and TNM stage of patients (all P<0.01), but not significantly related with patient's age, gender, pathological type and BRAF mutation (all P>0.05). In vitro overexpression of UCHL5 in KTC-1 and WRO cells could significantly promote BRAF expression, cell proliferation and metastasis (all P<0.01). Conclusion: The expression of UCHL5 is low in TC tissue, but upregulated with tumor progression. The high expression of UCHL5 in TC patients suggests poor prognosis. Meanwhile, UCHL5 can promote the malignant behaviors of TC cells in vitro.
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PURPOSE: Vascular smooth muscle cell (VSMC) proliferation induced by native low-density lipoprotein (nLDL) stimulation is dependent on superoxide production from activated NADPH oxidase. The present study aimed to investigate whether the novel arginase inhibitor limonin could suppress nLDL-induced VSMC proliferation and to examine related mechanisms. MATERIALS AND METHODS: Isolated VSMCs from rat aortas were treated with nLDL, and cell proliferation was measured by WST-1 and BrdU assays. NADPH oxidase activation was evaluated by lucigenin-induced chemiluminescence, and phosphorylation of protein kinase C (PKC) βII and extracellular signal-regulated kinase (ERK) 1/2 was determined by western blot analysis. Mitochondrial reactive oxygen species (ROS) generation was assessed using MitoSOX-red, and intracellular L-arginine concentrations were determined by high-performance liquid chromatography (HPLC) in the presence or absence of limonin. RESULTS: Limonin inhibited arginase I and II activity in the uncompetitive mode, and prevented nLDL-induced VSMC proliferation in a p21Waf1/Cip1-dependent manner without affecting arginase protein levels. Limonin blocked PKCβII phosphorylation, but not ERK1/2 phosphorylation, and translocation of p47phox to the membrane was decreased, as was superoxide production in nLDL-stimulated VSMCs. Moreover, mitochondrial ROS generation was increased by nLDL stimulation and blocked by preincubation with limonin. Mitochondrial ROS production was responsible for the phosphorylation of PKCβII. HPLC analysis showed that arginase inhibition with limonin increases intracellular L-arginine concentrations, but decreases polyamine concentrations. L-Arginine treatment prevented PKCβII phosphorylation without affecting ERK1/2 phosphorylation. CONCLUSION: Increased L-arginine levels following limonin-dependent arginase inhibition prohibited NADPH oxidase activation in a PKCβII-dependent manner, and blocked nLDL-stimulated VSMC proliferation.
Subject(s)
Animals , Rats , Aorta , Arginase , Arginine , Blotting, Western , Bromodeoxyuridine , Cell Proliferation , Chromatography, High Pressure Liquid , Chromatography, Liquid , Lipoproteins , Luminescence , Membranes , Muscle, Smooth, Vascular , NADP , NADPH Oxidases , Phosphorylation , Phosphotransferases , Protein Kinase C , Reactive Oxygen Species , SuperoxidesABSTRACT
Arginase inhibition exhibits beneficial effects in vascular endothelial and smooth muscle cells. In human aortic smooth muscle cells (hAoSMCs), native low-density lipoprotein (nLDL) induced the production of interleukin-8 (IL-8) that is involved in the pathogenesis of cardiovascular diseases. Therefore, we examined the effect of arginase inhibition on IL-8 production and the underlying mechanism. In hAoSMCs, reverse transcription–PCR, western blotting and immunocytochemistry with MitoTracker confirmed that arginase II was confined predominantly to mitochondria. The mitochondrial membrane potential (MMP) was assessed using tetramethylrhodamine ethyl ester. The MMP decreased upon nLDL stimulation but was restored upon arginase inhibition. MMP loss caused by nLDL was prevented by treatment with the intracellular Ca(2+) chelator BAPTA-AM. In mitochondrial Ca(2+) measurements using Rhod-2 AM, increased mitochondrial Ca(2+) levels by nLDL were inhibited upon preincubation with an arginase inhibitor. Among the polyamines, spermine, an arginase activity-dependent product, caused mitochondrial Ca(2+) movement. The nLDL-induced MMP change resulted in p38 mitogen-activated protein kinase (MAPK) phosphorylation and IL-8 production and was prevented by the arginase inhibitors BAPTA and ruthenium 360. In isolated AoSMCs from ApoE(−/−) mice fed a high-cholesterol diet, arginase activity, p38 MAPK phosphorylation, spermine and mitochondrial Ca(2+) levels and keratinocyte-derived chemokine (KC) production were increased compared with wild-type (WT) mice. However, in AoSMCs isolated from arginase II-null mice, increases in MMP and decreases in mitochondrial Ca(2+) levels were noted compared with WT and were associated with p38 MAPK activation and IL-8 production. These data suggest that arginase activity regulates the change in MMP through Ca(2+) uptake that is essential for p38 MAPK phosphorylation and IL-8 production.
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Many studies of protein expression after traumatic brain injury (TBI) have identified biomarkers for diagnosing or determining the prognosis of TBI. In this study, we searched for additional protein markers of TBI using a fluid perfusion impact device to model TBI in S-D rats. Two-dimensional gel electrophoresis and mass spectrometry were used to identify differentially expressed proteins. After proteomic analysis, we detected 405 and 371 protein spots within a pH range of 3-10 from sham-treated and contused brain cortex, respectively. Eighty protein spots were differentially expressed in the two groups and 20 of these proteins were identified. This study validated the established biomarkers of TBI and identified potential biomarkers that could be examined in future work.
Muitos estudos de expressão proteica após lesão cerebral traumática (LCT) identificam biomarcadores para determinação diagnóstica ou prognóstica do LCT. No presente estudo, foram investigados marcadores proteicos adicionais de LCT, através de um aparelho de impacto no fluxo e perfusão em ratos S-D. Eletroforese bidimensional em gel e espectrometria de massa foram utilizadas para identificar diferentes proteínas expressas. Após a análise proteômica, detectamos marcas de proteínas 405 e 371, com pH variando entre 3-10 no córtex de ratos sham e naqueles com contusão cerebral, respectivamente. Oitenta marcas proteicas foram expressas nos dois grupos e 20 destas proteínas foram identificadas. Este estudo validou o estabelecimento de biomarcadores de LCT e identificou potencial biomarcadores que poderão ser estudados em estudos futuros.
Subject(s)
Animals , Male , Biomarkers/analysis , Brain Injuries/diagnosis , Cerebral Cortex/chemistry , Proteomics , Brain Chemistry , Brain Injuries/metabolism , Disease Models, Animal , Electrophoresis, Gel, Two-Dimensional , Mass Spectrometry , Prognosis , Random Allocation , Rats, Sprague-Dawley , Reference Values , Time FactorsABSTRACT
Background & objectives: Tuberculosis (TB) bacilli ingested by macrophages evade host immune responses by multiple mechanisms including the inhibition of apoptosis. As the cytochrome-P-450 system (CYP) contributes to apoptosis it has been suggested that genetic variation in CYP may be associated with susceptibility to TB infection. This study was carried out to evaluate cytochrome P-450 polymorphisms in Chinese Han children and to investigate the effect of these polymorphisms in paediatric TB. Methods: Frequencies for the CYP2C19, CYP3A4, CYP3A5 and CYP2E1 mutated alleles and genotypes were compared between 142 Chinese paediatric TB patients and 150 non-infected controls by real time PCR genotyping on peripheral leukocyte DNA. Results: CYP2C19 (636 G>A, rs4986893) A allele and AG genotype were associated with decreased susceptibility to TB (P = 0.006, OR= 0.33, 95% CI: 0.15-0.76; and P = 0.005, OR =0.31, 95% CI: 0.14-0.72 respectively), as were the CYP3A5 (6986A>G, rs776746) G allele and particularly homozygous GG (recessive mode) genotype (P = 0.004, OR=0.61, 95% CI: 0.43-0.85; and P=0.002, OR=0.47, 95% CI: 0.29-0.76). Interpretation & conclusions: The data suggested that CYP2C19 and CYP3A5 polymorphisms affect susceptibility to paediatric TB. Further studies are indicated to confirm and elucidate these observations.
Subject(s)
Aryl Hydrocarbon Hydroxylases , Child , China , Cytochrome P-450 CYP3A/genetics , Humans , Polymorphism, Genetic , TuberculosisABSTRACT
Allergic asthma is a complex and chronic inflammatory airway disease. Interleukin-17 is a pro-inflammatory cytokine which plays critical role in the pathogenesis of allergic asthma. It has been reported that beta-arrestin2 regulated the development of allergic asthma at a proximal step in the inflammatory cascade. In this study, the influence of beta-arrestin2 on Interleukin-17 production and expression of CD4+ T lymphocytes in a murine asthma model was investigated. Splenic CD4+ T lymphocytes from wild-type mice and those from a murine asthma model were purified. CD4+ T lymphocytes from a murine asthma model were transfected with siRNAs targeting the beta-arrestin2 or were pretreated with the ERK1/2 inhibitor, PD98059. After stimulation, the protein expression of beta-arrestin2 phosphorylated-ERK1/2 and IL-17 were detection by Western blot; the mRNA expression of IL-17 were detected by real-time PCR; the accumulation of IL-17 in supernatants were detected by ELISA. We found that beta-arrestin2 phosphorylated-ERK1/2 and IL-17 expression in CD4+ T lymphocytes from a murine asthma model was increased compared with those from wildtype mice[p<0.01]. Treatment of CD4+ T lymphocytes with siRNAs targeting the beta-arrestin2 down-regulated phosphorylated- ERK 1/2 and IL-17 expression [p < 0.01]. PD98059 decreased IL-17 production and expression in CD4+ T lymphocytes in a murine asthma model [p < 0.05]. We conclude that beta-arrestin2 stimulated IL-17 production and expression of CD4+ T lymphocytes in a murine asthma model. The effect was partly mediated by ERK 1/2 activation. Targeting beta-arrestin2 biological activity could be a valid therapeutic approach for the treatment of allergic asthma
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<p><b>OBJECTIVE</b>To compare the clinical significance of PET/CT and MRI in diagnosing lymph node metastasis and N staging of nasopharyngeal carcinoma (NPC).</p><p><b>METHODS</b>116 NPC patients had undergone PET/CT and MRI before therapy. The findings of PET/CT and MRI in diagnosing lymph node metastasis and N staging were compared according to the results of follow-up.</p><p><b>RESULTS</b>A total of 614 lymph nodes in 116 patients were analyzed. 340 positive nodes and 274 negative nodes interpreted by image findings were verified during follow-up. The sensitivity, specificity and accuracy of PET/CT in diagnosing node metastasis was 93.2%, 98.2% and 95.4%, while that of MRI was 88.8%, 91.2% and 89.9%, respectively, with statistically significant difference in each between PET/CT and MRI (P < 0.05). Based on Fuzhou Staging System, 109 patients (94.0%) were correctly staged by PET/CT, and 103 patients (88.8%) by MRI, while according to UICC Staging System, 108 patients (93.1%) were correctly staged by PET/CT, and 100 patients (86.2%) by MRI.</p><p><b>CONCLUSION</b>PET/CT is superior to MRI in diagnosing lymph node metastasis and N staging of nasopharyngeal carcinoma. The false-positive and false-negative assessment based on PET-CT scan findings may be caused by: (1) inflammatory hyperplastic node; (2) node with large areas of necrosis; (3) node in diameter less than spatial resolution limitation of PET.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Diagnostic Errors , Follow-Up Studies , Lymph Nodes , Diagnostic Imaging , Pathology , Lymphatic Metastasis , Magnetic Resonance Imaging , Nasopharyngeal Neoplasms , Diagnosis , Pathology , Neoplasm Staging , Positron-Emission Tomography , Sensitivity and SpecificityABSTRACT
OBJECTIVES: The most frequently cited health related slogan in North Korea is that socialistic medicine is preventive medicine. It implies that North Korea puts preventive medicine at the operational center of its national health care system. This study aimed at examining and comparing preventive medicine practices in North Korea with those of South Korea. METHODS: Efforts have been made to obtain a textbook for analysis its contents. Many people have iassisted in the study by joining the interview. Some of these people are as follows: a former professor of PyongYang Medical School, NK physicians living in South Korea, WHO staffs, diplomatic officials, etc. The major items of analysis consisted of industrial medicine and hygiene, nutrition, school health, epidemiology, health statistics and heath policy & management. RESULTS: Public health philosophy is finely rooted and well integrated in the operation of the North Korean national health care system, particularly in the area of industrial medicine and hygiene. Preventive medicine with a strong health surveillance system spanning a number of broad social organizations is a major tool to improve the health of the people in North Korea. The emphasis on preventive medicine has a close relationship with the 'Juche Philosophy' and the shortage of pharmaceuticals and medical equipment. To cope with the shortage problem, North Korean health workers are encouraged to grow medicinal herbs. We have found that they put little effort into teaching newly emerging diseases, such as AIDS, VDT syndrome, hazards of EMF, and agricultural chemical poisonings. Of the subjects of the preventive medicine text, 78.9% coincide with those of South Korean industrial health manuals and 34.2% with South Korean epidemiology texts. However, an absolute difference was found to exist between the heath policies and management systems. CONCLUSION: In North Korea, the concept of preventive medicine functions as the basic philosophic strategy of the national health care system. It differs greatly from the South Korean system in both practice and educational content. Its contribution to society is simply incomparable to that of South Korea. More communication and further study is called for in order to improve the preventive medicine practices in the future.
Subject(s)
Delivery of Health Care , Democratic People's Republic of Korea , Epidemiology , Hygiene , Korea , Occupational Health , Occupational Medicine , Philosophy , Plants, Medicinal , Poisoning , Preventive Medicine , Public Health , School Health Services , Schools, MedicalABSTRACT
Most extended care facilities have admitted both the healthy and unhealthy elderly, among which members' average caring demand vary. The Aged Welfare Law, however, currently provides no reasonable basis on the staffing policy for extended care facilities. It just reflects the admitted number of the elderly rather than differences in members' average caring demand among facilities. This study is designed to estimate the need for caring staff on the basis of the correlation between the individual health status measured by various tools including Activities of Daily Living and caring demand by actual service time for each one. The sample included all of the admitted elderly(187 persons) in 4 extended care facilities, two in Seoul and the other two in KangWon-Do over the survey period October 5 through October 20, 1996. The survey process consisted of 3 stages. (1) The current staffing information was collected through self-completed written questionnaires left for head official in each facility. (2) Six graduate students at School of Public Health interviewed all residents to collect information on their health status and sociodemographics. The response rate for the interview was relatively high(85%). (3) Information on direct and indirect caring time consumed for each residents came from self-completed written questionnaires given to nurses and helpers in each target facilities. Analysis of the data was made using Pearson's correlation and multiple regression technique through SAS program. Based on this procedure, the following was found. 1. No facility meet the staffing standard in the Aged Welfare Law completely. 2. It is actual service time that is most correlated with ADL(Activities of daily living). 3. When all of the elderly are divided by four groups based on the level of ADL, the mean values of needed caring time in each group are 15, 21, 36 and 88 minutes respectively. 4. There is no significant difference among facilities in distribution of elderly person by group. 5. No facility meets the estimated number of nurses and helpers which reflects health status of the admitted elderly. Therefore, it is required that severity of the admitted elderly be considered in establishing staffing standard for extended care facility.
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Aged , Humans , Activities of Daily Living , Head , Jurisprudence , Public Health , Surveys and Questionnaires , Seoul , Skilled Nursing FacilitiesABSTRACT
This study has attempted to show general characteristics of health centre directors who have served the post of directorship during the last 40 years. Of 3,000 such health centre directors, information on about 2,500 directors was collected. While average length of service for health center directors has increased, that of vacancy period has decreased. Rural areas have a shorter average length of service than the urban area. Rural areas have twice longer length of vacancy period per health center. Kangwon-do has the longest average length of vacancy period since 1980(2.79 months/year), and Daejeon has the shortest length of vacancy period(0.21 months/year). Chung-buk has no physician directors. The civil servant's rank for the directorship has promoted from the fifth level to the fourth level since 1990. A comparison between the physician director and non-physician director was made as follows : First, the proportion of physician directors had maintained rather high before 1980s ; 62.5% in 1963, 78.3% in 1970, 70.4% in 1980. It decreased to 44.1% in 1990 and 47.6% in 1997. Instead, non-physician directors has abruptly increased since 1980s(12.4% in 1980, 55.4% in 1990 and 50.8% in 1997). Second, physician directors mainly locate in the urban area(58.0% in 1997), but non-physician directors mainly in the rural area(67.2% in 1997). Third, since 1980, the average length of service for physician directors and for non-physician directors has become similar. Fourth, the mean age of physician directors is 45.1 years, and that of non-physician directors 55.7 years. The latter is 10 years older than the former.
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Child , Humans , KoreaABSTRACT
No abstract available.
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No abstract available.