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Chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic respiratory disease characterised by irreversible airways obstruction associated with chronic airways inflammation and remodelling, while the pathogenesis and the mechanistic differences between patients remain to be fully elucidated. We previously reported that alarmin cytokine IL-33 may contribute to the production of autoantibodies against respiratory epithelial cells. Here we expand the hypothesis that pulmonary autoimmune responses induced by airway microbiota also contribute to the progression of COPD. We focused on Edwardsiella tarda which we detected uniquely in the induced sputum of patients with acute exacerbations of COPD. Pernasal challenge of the airways of WT mice with supernatants of cultured E. tarda induced marked, elevated expression of IL-33 in the lung tissues. Immunisation of animals with supernatants of cultured E. tarda resulted in significantly elevated airways inflammation, the formation of tertiary lymphatic structures and significantly elevated proportions of T follicular helper T cells in the lung tissue and mediastinal lymph nodes. Interestingly, such challenge also induced production of IgG autoantibodies directed against lung tissue lysate, alveolar epithelial cell proteins and elastin fragment, while putrescine, one of metabolites generated by the bacterium, might play an important role in the autoantibody production. Furthermore, all of these effects were partly but significantly abrogated in mice with deletion of the IL-33 receptor ST2. Collectively, these data support the hypothesis that COPD is progressed at least partly by airways microbiota such as E. tarda initiating autoimmune attack of the airways epithelium mediated at least partly through the IL-33-ST2 axis.
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Although contributions of IL-33 to pulmonary diseases, including asthma, have been well documented, the complexity of such regulation warrants additional exploration. To better understand the involvement of IL-33, we used a murine asthma surrogate based on sensitisation and challenge with dust mite extract in the presence/absence of IL-33. Murine models were established with Dermatophagoides farinae (Der f) to establish (1) the effect of co-administered rmIL-33; (2) the effect of prior glucocorticoid intervention; (3) the effect of IL-33 on challenge with sub-threshold dosage Der f. The effects of rmIL-33 on bone marrow-derived dendritic cells were explored in vitro. Mice challenged with Der f combined with IL-33 compared with diluent control evinced significantly more airways inflammation and local cytokine production which was less sensitive to inhibition by dexamethasone. IL-33 also induced airways hyperresponsiveness, eosinophilic inflammation and cytokine production in lung tissues of animals exposed to sub-threshold dosage of Der f. In vitro, IL-33-stimulated DCs showed a significantly elevated capacity to stimulate CD4+ T cell proliferation and cytokine production and were also significantly more resistant to dexamethasone-induced apoptosis. Our data suggest that IL-33 reduces the threshold for allergen-induced inflammation of the airways in acorticosteroid-resistant fashion possibly in part through acting on DCs, a phenomenon which may be relevant to the development of severe, corticosteroid-resistant airways obstruction in human asthmatic patients.
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Asma/imunologia , Linfócitos T CD4-Positivos/imunologia , Células Dendríticas/imunologia , Inflamação/imunologia , Interleucina-33/metabolismo , Sistema Respiratório/imunologia , Animais , Antialérgicos/uso terapêutico , Antígenos de Dermatophagoides/imunologia , Asma/tratamento farmacológico , Diferenciação Celular , Células Cultivadas , Dermatophagoides farinae , Dexametasona/uso terapêutico , Modelos Animais de Doenças , Resistência a Medicamentos , Feminino , Humanos , Inflamação/tratamento farmacológico , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Patients with atopic asthma may become sensitised to the grain storage mite Dermatophagoides farinae (Der f), the house dust mite Dermatophagoides pteronyssinus (Der p) or both, but thus far little attention has been paid to date to possible variation in their pathophysiological effects. Here we present a side by side comparison of the effects of extracts of these two dust mites in a murine surrogate of atopic asthma. Compared with the Der p-challenged mice, however, the mice-challenged with Der f had favour changes in lung tissue elasticity and expression in matrix metalloproteinases in lung tissue, while the mice challenged with Der p showed more neutrophils infiltrating around the airway and stronger expression of steroid-resistant related cytokines in the lung tissue. Our data suggest that different dust mite crude extracts might lead different pathological characteristics, at least in murine models of asthma.
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Antígenos de Dermatophagoides/imunologia , Asma/imunologia , Dermatophagoides farinae/imunologia , Dermatophagoides pteronyssinus/imunologia , Hipersensibilidade/imunologia , Animais , Misturas Complexas/imunologia , Misturas Complexas/farmacologia , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND AND OBJECTIVE: Isolated blockade of IL-25, IL-33 and thymic stromal lymphopoietin (TSLP) has been shown to reduce airways inflammation and hyperresponsiveness in murine asthma model. The hypothesis that combined blockade of all three cytokines can accomplish this more effectively has never been addressed. METHODS: We studied a murine asthma model employing sensitization and challenge with ovalbumin (OVA) or saline control. To discern the effects of IL-33 blockade, we compared outcomes in strain identical, wild-type and IL-33 receptor (St2 -/- ) gene-deleted mice. We then examined, in the St2 -/- animals, the effects of additional, single or combined blockade of IL-25 and TSLP with blocking antibodies. Outcomes included airways reactivity, inflammatory cellular infiltration, epithelial cell metaplasia, deposition of fibrosis-related proteins, local Th2-type cytokine expression and total and specific serum IgE concentrations measured by ELISA and quantitative immunohistochemistry. RESULTS: St2 -/- gene deletion significantly reduced airways reactivity, inflammatory cellular infiltration, lung tissue expression of Th2 cytokines and fibrosis related proteins and serum total IgE in response to OVA sensitization and challenge. Additional administration of anti-IL-25 and anti-TSLP blocking antibodies to the St2 -/- mice further significantly reduced inflammation, Th2 cytokine expression, airways fibrosis and IgE production, while anti-TSLP alone reduced eosinophil infiltration and local IL-4 expression. The airways inflammatory cellular infiltrate and lung tissue expression of Th2 cytokine, but not fibrosis-related proteins were also reduced in the presence of isotype identical, control antibodies. CONCLUSION: Combined blockade of these three cytokines may better ameliorate airways pathological changes in this murine asthma model, with implications for human asthma.
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Asma/patologia , Asma/terapia , Citocinas/antagonistas & inibidores , Interleucina-33/antagonistas & inibidores , Interleucina-33/genética , Interleucinas/antagonistas & inibidores , Remodelação das Vias Aéreas/fisiologia , Alérgenos/imunologia , Animais , Asma/imunologia , Modelos Animais de Doenças , Eosinófilos/imunologia , Inflamação/metabolismo , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Ovalbumina/farmacologia , Linfopoietina do Estroma do TimoRESUMO
The mechanisms underlying the chronic, progressive airways inflammation, remodelling and alveolar structural damage characteristic of human chronic obstructive pulmonary disease (COPD) remain unclear. In the present study, we address the hypothesis that these changes are at least in part mediated by respiratory epithelial alarmin (IL-33)-induced production of autoantibodies against airways epithelial cells. Mice immunized with homologous, syngeneic lung tissue lysate along with IL-33 administered directly to the respiratory tract or systemically produced IgG autoantibodies binding predominantly to their own alveolar type II epithelial cells, along with increased percentages of Tfh cells and B2 B-cells in their local, mediastinal lymph nodes. Consistent with its specificity for respiratory epithelial cells, this autoimmune inflammation was confined principally to the lung and not other organs such as the liver and kidney. Furthermore, the serum autoantibodies produced by the mice bound not only to murine, but also to human alveolar type II epithelial cells, suggesting specificity for common, cross-species determinants. Finally, concentrations of antibodies against both human and murine alveolar epithelial cells were significantly elevated in the serum of patients with COPD compared with those of control subjects. These data are consistent with the hypothesis that IL-33 contributes to the chronic, progressive airways obstruction, inflammation and alveolar destruction characteristic of phenotypes of COPD/emphysema through induction of autoantibodies against lung tissue, and particularly alveolar type II epithelial cells.
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Células Epiteliais Alveolares/imunologia , Autoanticorpos/imunologia , Subpopulações de Linfócitos B/imunologia , Interleucina-33/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Células Epiteliais Alveolares/patologia , Animais , Autoenxertos , Subpopulações de Linfócitos B/patologia , Modelos Animais de Doenças , Humanos , Linfonodos/imunologia , Linfonodos/patologia , Mediastino/patologia , Camundongos , Doença Pulmonar Obstrutiva Crônica/patologiaRESUMO
It has been suggested that interleukin-33 (IL-33) plays an important role in the pathogenesis of asthma through a variety of pathways, but its role in airways fibrosis in asthma has not been fully elucidated. In the present study we evaluated changes in the expression of extracellular matrix proteins (ECMs) as well as matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in an IL-33-induced, antigen-independent murine surrogate of asthma as well as a conventional surrogate employing per-nasal challenge of mice previously sensitized to produce an IgE response to ovalbumin (OVA). In addition, in in vitro experiments we explored the direct effects of IL-33 on the proliferation and function of murine fibroblasts. Per-nasal administration of IL-33 alone was sufficient to induce airways deposition of ECMs, including collagens I, III, V and fibronectin, to a degree comparable with that observed in the OVA-sensitized and challenged mice. These changes were associated with a local imbalance between the expression of extracellular MMPs and TIMPs. Per-nasal challenge of mice with IL-33 also induced elevated airways expression of connective tissue growth factor and fibroblast growth factor receptor 4, two key facilitators of local fibrosis, again to a degree compatible with that observed in OVA-sensitized and challenged mice. Deletion of the ST2 gene, which encodes the IL-33 receptor, abrogated these fibrotic changes in the airways in the OVA surrogate. In vitro, IL-33 significantly increased the proliferation and expression of collagen III by murine lung fibroblasts. These data suggest that direct exposure of murine airways to IL-33 is able to induce local fibrotic changes, at least partially through effects of signalling through the IL-33/ST2 axis on fibroblast function and local expression of MMPs and their inhibitors, and other fibrosis-related proteins.
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OBJECTIVE: Palliative care consultation is relevant for patients requiring Venous-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO); however, evidence is limited to support its value. For this population, we compared length of stay (LOS) (primary outcome), operational metrics and goals of care (GOC) frequency before and after a collaboration between cardiothoracic (CT) surgery and Geriatrics and Palliative Medicine (GaP). METHODS: Retrospective chart review of patients (18+) admitted to a quaternary center that required VA-ECMO between 2019-2021 and received GaP consultation. Demographics, LOS, times to consult, illness severity, GOC, and outcomes were analyzed. RESULTS: 120 patients met inclusion criteria and 64 (53.3%) had GaP consultation. No differences were observed regarding demographics and insertion status (emergent vs elective). Median (IQR) days to GaP consult for 2019, 2020 and 2021 were 6.5 (4.0-14.5), 5.0 (2.0-11.0) and 3.0 (2.0-5.0), respectively (P = .006). Median days from insertion to consult for 2019, 2020 and 2021 were 6.0 (4.0-20.0), 3.0 (1.0-6.0) and 2.0 (1.0-4.0) (P = .003). Among survivors, over the 3-year course, median LOS was not statistically different. Between expired patients, median (IQR) LOS for 2019, 2020, and 2021 was 28.5 (23.0-40.0), 12.0 (8.0-14.0), 11.0 (5.0-17.0) days (P = .013). For patients not seen by GaP, 8 (14.3%) GOC notes were documented, compared with 42 (65.6%) for patients seen. Mortality was similar (53.6% vs 53.1% [GaP]). CONCLUSION: For patient on VA-ECMO, early GaP consultation may improve hospital LOS and GOC rates. We suggest organizations consider early palliative integration when instituting mechanical circulatory support.
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OBJECTIVE: To measure the rate of high-risk group and the detection rate of colorectal cancer (CRC) in communities in Guangdong province and to provide scientific rationales for formulating mass screening plans in high-risk group. METHODS: Mass survey was conducted by questionnaire combined fecal occult blood test (FOBT) in Huizhou region, Guangdong Province, to sort out the high-risk population of CRC. Then the high-risk population was screened by colonoscopy and pathology to identify CRC. The differences were compared by direct expenditure which was used to calculate screening cost. RESULTS: A total of 68,953 people were surveyed. There were 940 people in high-risk group (detection rate: 1.36%), 3118 in immunity FOBT positive group (detection rate: 4.52%), Merging aforementioned two groups, there were 3870 in population at risk (detection rate: 5.61%). The CRC detection rate in high-risk group, immunity FOBT positive group, population at risk and average-risk group was 506.3/10(5), 314.3/10(5), 315.9/10(5) and 17.7/10(5) respectively. The positive predictive value of CRC screening scheme by high-risk group questionnaire-colonoscopy was 0.43% while CRC screening scheme by FOBT-colonoscopy 0.22%. In terms of direct expenditure of CRC per case in high-risk group and immunity FOBT positive group was 47,834.5 yuan and 82,303.6 yuan. The latter was 1.7 times than that of the former. CONCLUSIONS: The scheme of questionnaire combined FOBT for CRC is an effective way in mass survey. The scheme by high-risk group questionnaire-colonoscopy has a much better cost-effectiveness than that of the scheme by FOBT-colonoscopy so that it should be one of the preferred methods for individual screening in high-risk group.
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Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controle , Programas de Rastreamento/economia , Inquéritos e Questionários , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Análise Custo-Benefício , Humanos , Lactente , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: This study was conducted to investigate the treatment efficacies and immunological mechanisms of action of dioscin in mice with chicken collagen type II-induced arthritis (CIA). METHODS: The CIA mice was randomly divided into the model group (M), dioscin group (D), and tripterygium group (T); a normal control group (C) was also included. Each group was orally administered with related drugs or an equal volume of solvent (group C) starting on the 21st day of primary immunity, after which the levels of T helper 17 cells (Th17), regulatory T cells (Tregs), and their related factors were detected on the 35th day. RESULTS: Compared to group C, group M exhibited significantly increased levels of interleukin 17 (IL-17) and IL-6 and decreased IL-27 (p < 0.05). Group D exhibited significantly decreased levels of IL-17 and IL-6 compared with group M (p < 0.05). Group M showed a significantly increased ratio of Th17 cells (p < 0.05), while dioscin significantly reduced this ratio (p < 0.05). Groups M and C showed no significant difference in the ratio of Tregs (p > 0.05) but dioscin significantly increased this ratio (p < 0.05). Group M significantly increased signal transducer and activator of transcription 3 (STAT3) and STAT5 compared with that in group C (p < 0.05), while the T and D groups showed significantly reduced levels of STAT3 and STAT5 (p < 0.05). CONCLUSION: Dioscin may affect the differentiation of Th17 and Tregs and secretion of related factors by regulating CD4 T cell subset-related signal transduction and the expression of transcription-activating factor STAT3 and STAT5, thus exerting useful immunoregulatory roles in CIA mice.
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Artrite Experimental/tratamento farmacológico , Diosgenina/análogos & derivados , Linfócitos T Reguladores/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Animais , Artrite Experimental/imunologia , Galinhas , Colágeno Tipo II , Diosgenina/farmacologia , Interleucina-17/sangue , Interleucina-6/sangue , Interleucinas/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos DBA , Fator de Transcrição STAT3/análise , Fator de Transcrição STAT5/análise , Linfócitos T Reguladores/imunologia , Células Th17/imunologiaRESUMO
OBJECTIVE: To explore the epidemiology characteristics of colorectal cancer on community group in Guangdong province. METHODS: Huidong was took as the research spot to investigate the sickness and incidence of colorectal cancer among a whole community group in Guangdong province, and two projects were used simultaneously: "screening of colorectal cancer in high risk group" and "screening project using fecal occult blood test". The numeration time for population of 10 towns was set at July 1, 2005. Five towns were sampled out from Huidong with 100,859 persons. Meanwhile, the diseases and death cause registering system was established. RESULTS: The incidence of colorectal cancer in Huidong community group was 15.2/100,000 (male 17.2/100,000, female 13.0/100,000), the age-adjusted incidence was 17.6/100,000 (male 19.5/100,000, female 16.7/100,000). The morbidity was 41.9/100,000 (male 46.5/100,000, female 37.2/100,000), the age-adjusted morbidity was 49.0/100,000 (male 54.1/100,000, female 45.6/100,000). The mortality was 5.0/100,000 (male 5.9/100,000, female 4.0/100,000) and the age-adjusted morbidity was 6.4/100,000 (male 7.2/100,000, female 5.7/100,000). CONCLUSION: The incidence of colorectal cancer in Huidong community group is lower than that of high incidence area in China, but gets close to the normal incidence area of China and general level of the world.
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Neoplasias Colorretais/epidemiologia , Características de Residência/estatística & dados numéricos , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Prevalência , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To confirm the role of Tiam1 (T lymphoma invasion and metastasis 1) gene in the proliferation and metastasis of colorectal cancer. METHODS: Proliferative and metastatic abilities of Tiam1 transfectant were investigated by subcutaneous injection of cells and surgical orthotopic transplantation (SOI) in mice. RESULTS: The expression of Tiam1 led to a pronounced increase in HT29/Tiam1 cell growth starting from day 7, up to 2.5 fold increase of tumor volume at day 20 post injection. Tumors in the HT29/Tiam1 group receiving surgical orthotopic implantation were significantly heavier than those in HT29/mock group (t = -14.916, P < 0.01). In vivo metastasis assay by SOI showed that in HT29/Tiam1 group, 7/7 of mice developed peritoneal metastases and 4/7 had hepatic lesions. In addition, one of the seven HT29/Tiam1 group mice had tumors in lung, spleen and lymph nodes. In the HT29/mock group, only 2/7 of animals had peritoneal metastases and none produced detectable tumor in the liver. CONCLUSIONS: Tiam1 gene plays an important role in the proliferation, invasion and metastasis of colorectal cancer. It may serve as a useful clinical marker for tumor progression and metastasis of colorectal cancer.
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Proliferação de Células , Neoplasias Colorretais/patologia , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Neoplasias Peritoneais/secundário , Animais , Biomarcadores Tumorais/análise , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/fisiologia , Células HT29 , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Metástase Linfática , Camundongos , Camundongos Nus , Invasividade Neoplásica , Transplante de Neoplasias , Plasmídeos , Proteína 1 Indutora de Invasão e Metástase de Linfoma de Células T , Transfecção , Carga TumoralRESUMO
OBJECTIVE: We investigated and compared the functionality of two 3D visualization software provided by a CT vendor and a third-party vendor, respectively. Using surgical anatomical measurement as baseline, we evaluated the accuracy of 3D visualization and verified their utility in computer-aided anatomical analysis. METHODS: The study cohort consisted of 50 adult cadavers fixed with the classical formaldehyde method. The computer-aided anatomical analysis was based on CT images (in DICOM format) acquired by helical scan with contrast enhancement, using a CT vendor provided 3D visualization workstation (Syngo) and a third-party 3D visualization software (Mimics) that was installed on a PC. Automated and semi-automated segmentations were utilized in the 3D visualization workstation and software, respectively. The functionality and efficiency of automated and semi-automated segmentation methods were compared. Using surgical anatomical measurement as a baseline, the accuracy of 3D visualization based on automated and semi-automated segmentations was quantitatively compared. RESULTS: In semi-automated segmentation, the Mimics 3D visualization software outperformed the Syngo 3D visualization workstation. No significant difference was observed in anatomical data measurement by the Syngo 3D visualization workstation and the Mimics 3D visualization software (P>0.05). CONCLUSIONS: Both the Syngo 3D visualization workstation provided by a CT vendor and the Mimics 3D visualization software by a third-party vendor possessed the needed functionality, efficiency and accuracy for computer-aided anatomical analysis.
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Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Software , Adulto , Artérias/anatomia & histologia , Automação , Osso e Ossos/anatomia & histologia , Cadáver , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Pele/anatomia & histologia , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To explore the clinical characteristics and pattern of incidence of colorectal cancers in Guangdong region. METHODS: Analysis and summary were made for 3870 colorectal cancer patients pathologically confirmed in the Nanfang Hospital and Huizhou Municipal Central Hospital of Guangdong province. RESULTS: Median age of 3870 cases with colorectal cancer was 55.3. The high-risk age ranged from 41 to 70.204 cases among them were young patients (age < or = 30, 5.3%). With increase of age the number of cases with rectal cancers decreased gradually, while cancers occurring in the right hemi colon increased gradually. The ratio between male and female was 1.42:1. There were altogether 3958 colonic cancer lesions found in all the cases. Among them 3783 (97.8%) cases presented with a single lesson, 87 (2.2%) cases presented with multiple lesions. 2243 (56.7%) lesions located in the rectum, 717 (18.1%) in the left hemi colon, 998 (25.2%) in the right hemi colon. Histological types in all the lesions cases were grouped as follows: tubular adenocarcinoma 2943 (76.0%); papillary adenocarcinoma 256 (6.6%); mucinous carcinoma 425 (11.0%); and miscellaneous types 246 (6.4%). Colorectal cancers with poor differentiation occurring in the young were 38.2% while in the middle age and the elderly were 29.9% and 14.6%, respectively. The difference between two groups showed a statistical significance (P < 0.01). The cases with confirmed stage A, B, C and D were 234 (6.0%), 1936 (50.0%), 1310 (33.9%) and 390 (10.1%), respectively, according to Dukes' staging system. The cases with the progressing stages (B, C, D stages) were 3636 (94.0%) among all the cases. CONCLUSIONS: The number of patients with colorectal cancer admitted in hospital increased gradually in the recent 20 years, and showed a trend with the decrease percentage in rectal cancer and the gradual increasing in right hemi colon cancer with increase of patients age. Half of the colorectal cancer occurred in the rectum, the rest occurred in the left and right hemi colon. The three clinical epidemiological characteristics of colorectal cancer, which once existed in Chinese, has disappeared in Guangdong region.
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Neoplasias Colorretais/epidemiologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Criança , China/epidemiologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: To assess the risk factors of gastroesophageal reflux disease (GERD) in the general population and its impact on health-related quality of life (HRQOL). METHODS: A face-to-face interview was carried out in Guangdong Province using a validated Chinese version Reflux Disease Questionnaire (RDQ) to assess the prevalence of GERD. Random clustered sampling of permanent inhabitants aged 18 to 90 years was carried out under stratification of urban and suburban areas. The impact of GERD on HRQOL was evaluated using the Chinese version of SF-36. The statistical analysis was performed with SPSS 10.0 programs. RESULTS: A total of 83 GERD patients were collected and 166 healthy subjects were selected as control. There was no difference in prevalence between male (2.6%) and female (2.4%). There was no significant association between age and prevalence of GERD symptoms. Divorced/widowed/separated subjects (OR 4.61) and subjects with severe working burden (OR 3.43) were significantly more likely to report GERD symptoms. As compared with the general population, subjects with GERD symptoms experienced considerable impairment in quality of life. CONCLUSIONS: Psychosocial factors may play important roles in the production of GERD symptoms. GERD has a negative impact on HRQOL.
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Refluxo Gastroesofágico/epidemiologia , Qualidade de Vida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Refluxo Gastroesofágico/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , População Rural , Estudos de Amostragem , Inquéritos e Questionários , População UrbanaRESUMO
OBJECTIVE: To study the trend of clinical characteristics of colorectal cancer during the past 20 years in Gaungdong province. METHODS: The clinical data of 3870 cases of colorectal cancers confirmed pathologically who were hospitalized to Nanfang Hospital and Huizhou Municipal Hospital, Guangdong province, 1985 - 2004 were divided into 5-year groups and analyzed. RESULTS: The hospitalization number of colorectal cancer in the 2000 - 20004 5-year period was 102%, higher than that of the 1985 - 1989 period with an annual increase of 5.1%. The median age of incidence 2000 - 2004 was 58.6 years, 8.4 years higher than that in 1985 - 1989. The male to female ratio of the 3870 patients was 1.42:1. The male to female ratio 2000 - 2004 was 1.35:1, lower than that 1985 - 1989 (1.50:1). The proportion of rectal cancer 2000 - 2004 was 49.7%, significantly lower than that in 1985 - 1989 (64.8%), while the proportion of right hemi-colon cancer 2000 - 2004 was 28.7%, significantly higher than that in 1985 - 1989 (18.0%). The proportion of moderately and well differentiated cancer 2000 - 2004 was 80.6%, higher than that in 1985 - 1989 (70.1%), and the proportion of poorly differentiated cancer 2000 - 2004 was 19.4%, lower than that in 1985 - 1989 (29.9%). The proportion of colorectal cancer at Dukes A stage 2000 - 2004 was 9.8%, higher than that in 1985 - 1989 (3.2%). CONCLUSION: In the past 20 years, the incidence of colorectal cancer has increased in Guangdong province with a n increase of median age of incidence, The male to female ratio has decreased, and the incidence of right hemi-colon cancer, the rates of higher differentiated cancer and Dukes A stage cancer have increased.
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Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Criança , China/epidemiologia , Feminino , Hospitalização/estatística & dados numéricos , Hospitalização/tendências , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
The aim of this study was to detect the therapeutic effect of dioscin on collagen-induced arthritis (CIA). Mice model of CIA was induced by chicken collagen II and arthritis index was assessed. After suspension of dioscin (100mg/kg/d) or triptolide was intragastrically administered, the left paw swelling and body weight of each mouse were measured. Then tissue samples were assayed by histopathological analysis. The levels of Th1 and Th2 were detected by flow cytometry. The expression of p-STAT1, p-STAT4 and p-STAT6 was demonstrated by western blot analysis, and T-bet and GATA-3 expression was detected by RT-PCR. The paw swelling and arthritis index were decreased and body weight was increased in the high dose of dioscin group compared to the model group (P<0.05). Histopathological analysis revealed that the damage of synovium tissue in dioscin and triptolide group alleviated. The ratio of Th1/Th2 in the dioscin group (0.82±0.24) and triptolide group (0.99±0.44) was lower than that in the model group (1.84±0.70, P<0.05). Additionally, p-STAT4 expression was decreased, and both p-STAT6 and GATA3 expression was increased in the dioscin group than that in the model group (P<0.05). Dioscin might have some therapeutic effects on CIA through regulating the proportion of Th1/Th2 cells, which could reduce the expression of p-STAT4, increase the expression of p-STAT6 and GATA3 in the synovial tissue.
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Anti-Inflamatórios/uso terapêutico , Artrite Experimental/tratamento farmacológico , Dioscorea/imunologia , Diosgenina/análogos & derivados , Membrana Sinovial/efeitos dos fármacos , Células Th1/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Animais , Colágeno Tipo II/imunologia , Diosgenina/uso terapêutico , Modelos Animais de Doenças , Diterpenos/uso terapêutico , Compostos de Epóxi/uso terapêutico , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos DBA , Fenantrenos/uso terapêutico , Fatores de Transcrição STAT/genética , Fatores de Transcrição STAT/metabolismo , Membrana Sinovial/patologia , Células Th1/imunologia , Equilíbrio Th1-Th2/efeitos dos fármacos , Células Th2/imunologiaRESUMO
OBJECTIVE: To investigate whether the Tiam1 gene expression enhances the invasive and metastatic capabilities of colorectal carcinoma cells. METHODS: Endogenous expression of Tiam1 in five colorectal carcinoma cell lines was investigated by RT-PCR. Tiam1/C1199HA cDNA was transfected into HT29, a colorectal carcinoma cell line without endogenous Tiam1 expression. RNA and protein expression of Tiam1 gene in the transfectants were detected by RT-PCR, immunohistochemistry and Western blot respectively. The biological behaviors of the transfectants were investigated by MTT and in-vitro invasion assays. RESULTS: Tiam1 gene was highly expressed in LoVo and SW620 cells. Low level expression was seen in HCT116 and SW480 and no expression was found in HT29. Transfection of Tiam1 significantly increased the proliferation of HT29 cells along with markedly enhanced in-vitro invasion and metastasis. CONCLUSIONS: Tiam1 gene plays an important role in the invasion and metastasis of colorectal carcinoma. It may be a useful marker for metastasis of colorectal carcinoma.
Assuntos
Proliferação de Células , Neoplasias Colorretais/patologia , Fatores de Troca do Nucleotídeo Guanina/genética , Biomarcadores Tumorais , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Fatores de Troca do Nucleotídeo Guanina/fisiologia , Células HT29 , Humanos , Invasividade Neoplásica , Metástase Neoplásica , Proteína 1 Indutora de Invasão e Metástase de Linfoma de Células T , TransfecçãoRESUMO
OBJECTIVE: To explore and assess the health-related quality of life (HRQOL) of irritable bowel syndrome (IBS) patients in the population. METHODS: Random clustered sampling involving permanent inhabitants aged 18 - 80 yr was carried out under stratification of urban and suburban areas in Guangdong Province. Altogether 231 IBS patients fulfilling the Rome II criteria and 636 Non-IBS as control were collected. The impact of IBS on HRQOL was evaluated using the Chinese version of SF-36. RESULTS: (1) There were no statistically significant differences between IBS and Non-IBS groups in aspects of sex, age educational level, and distribution according to areas (P > 0.05). (2) IBS patients reported significantly poorer HRQOL than controls (Non-IBS) on all SF-36 subscales (P < 0.05). The patients had poorer HRQOL than the Non-patients, but their differences weren't significant (P > 0.05). (3) The scores on all SF-36 subscales were highly associated with the frequency of abdominal pain in IBS patients (P < 0.05); They were also correlated to degree of effects of IBS symptoms on life reported by IBS patients (P < 0.05); The association between the scores and the symptom of fatigue which is the most extra-intestinal symptom in IBS was significant (P < 0.05); (4) Copying style was highly correlated to the eight SF-36 subscales; IBS still had a significant impact on patients after partialing out the effect of copying style. CONCLUSIONS: IBS symptoms had a negative impact on HRQOL and the SF-36 could be adopted to detect the differences between IBS group and Non-IBS group, which may be used as an outcome measure in future treatment studies. However, the development of IBS-specific measures of quality of life is necessary.
Assuntos
Síndrome do Intestino Irritável/psicologia , Qualidade de Vida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Síndrome do Intestino Irritável/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To explore the prevalence of irritable bowel syndrome (IBS) and its risk factors in Guangdong province. METHODS: A questionnaire was used to screen IBS by face-to-face interviews according to Manning (modified including symptoms of constipation) and Rome II criteria. Random clustered sampling involving permanent inhabitants aged 18 - 80 years was carried out under stratification of urban and suburban areas. Potential risk factors were explored by comparing the frequencies among IBS group and non-IBS group using chi(2) and logistic analysis of multivariate adjusted for age and gender. RESULTS: A total of 4178 residents (male 1907, female 2271) were investigated. Mean age among the responders was (43 +/- 14) years. The response rate was 98%. The adjusted prevalence of IBS in Guangdong province is 5.67% according to the modified Rome II criteria, and is 11.50% according to Manning criteria. There is no difference between urban and suburban areas. The female was predominant in IBS, and the ratio of male to female was 1:1.25 (Rome II) and 1:1.34 (Manning). The age was poorly correlated with the prevalence. Events including history of analgesic use such as NSAID (OR = 3.83), history of food allergies (OR = 2.68), psychological distress (OR = 2.18), life events (OR = 1.89), history of dysentery (OR = 1.63) and negative coping style (OR = 1.28) are highly associated with IBS (P < 0.05). CONCLUSION: IBS is a common disorder in Guangdong Province which deserves greater care and further investigation.