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1.
Sci Adv ; 10(18): eadl3747, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38701212

RESUMO

Early-life tobacco exposure serves as a non-negligible risk factor for aging-related diseases. To understand the underlying mechanisms, we explored the associations of early-life tobacco exposure with accelerated biological aging and further assessed the joint effects of tobacco exposure and genetic susceptibility. Compared with those without in utero exposure, participants with in utero tobacco exposure had an increase in Klemera-Doubal biological age (KDM-BA) and PhenoAge acceleration of 0.26 and 0.49 years, respectively, but a decrease in telomere length of 5.34% among 276,259 participants. We also found significant dose-response associations between the age of smoking initiation and accelerated biological aging. Furthermore, the joint effects revealed that high-polygenic risk score participants with in utero exposure and smoking initiation in childhood had the highest accelerated biological aging. There were interactions between early-life tobacco exposure and age, sex, deprivation, and diet on KDM-BA and PhenoAge acceleration. These findings highlight the importance of reducing early-life tobacco exposure to improve healthy aging.


Assuntos
Envelhecimento , Predisposição Genética para Doença , Efeitos Tardios da Exposição Pré-Natal , Humanos , Feminino , Masculino , Efeitos Tardios da Exposição Pré-Natal/genética , Envelhecimento/genética , Adulto , Gravidez , Nicotiana/efeitos adversos , Nicotiana/genética , Fumar/efeitos adversos , Fatores de Risco , Pessoa de Meia-Idade
2.
Int J Surg ; 110(2): 820-831, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38016139

RESUMO

BACKGROUND: Accurate prognostication of oncological outcomes is crucial for the optimal management of patients with renal cell carcinoma (RCC) after surgery. Previous prediction models were developed mainly based on retrospective data in the Western populations, and their predicting accuracy remains limited in contemporary, prospective validation. We aimed to develop contemporary RCC prognostic models for recurrence and overall survival (OS) using prospective population-based patient cohorts and compare their performance with existing, mostly utilized ones. METHODS: In this prospective analysis and external validation study, the development set included 11  128 consecutive patients with non-metastatic RCC treated at a tertiary urology center in China between 2006 and 2022, and the validation set included 853 patients treated at 13 medical centers in the USA between 1996 and 2013. The primary outcome was progression-free survival (PFS), and the secondary outcome was OS. Multivariable Cox regression was used for variable selection and model development. Model performance was assessed by discrimination [Harrell's C-index and time-dependent areas under the curve (AUC)] and calibration (calibration plots). Models were validated internally by bootstrapping and externally by examining their performance in the validation set. The predictive accuracy of the models was compared with validated models commonly used in clinical trial designs and with recently developed models without extensive validation. RESULTS: Of the 11  128 patients included in the development set, 633 PFS and 588 OS events occurred over a median follow-up of 4.3 years [interquartile range (IQR) 1.7-7.8]. Six common clinicopathologic variables (tumor necrosis, size, grade, thrombus, nodal involvement, and perinephric or renal sinus fat invasion) were included in each model. The models demonstrated similar C-indices in the development set (0.790 [95% CI 0.773-0.806] for PFS and 0.793 [95% CI 0.773-0.811] for OS) and in the external validation set (0.773 [0.731-0.816] and 0.723 [0.731-0.816]). A relatively stable predictive ability of the models was observed in the development set (PFS: time-dependent AUC 0.832 at 1 year to 0.760 at 9 years; OS: 0.828 at 1 year to 0.794 at 9 years). The models were well calibrated and their predictions correlated with the observed outcome at 3, 5, and 7 years in both development and validation sets. In comparison to existing prognostic models, the present models showed superior performance, as indicated by C-indices ranging from 0.722 to 0.755 (all P <0.0001) for PFS and from 0.680 to 0.744 (all P <0.0001) for OS. The predictive accuracy of the current models was robust in patients with clear-cell and non-clear-cell RCC. CONCLUSIONS: Based on a prospective population-based patient cohort, the newly developed prognostic models were externally validated and outperformed the currently available models for predicting recurrence and survival in patients with non-metastatic RCC after surgery. The current models have the potential to aid in clinical trial design and facilitate clinical decision-making for both clear-cell and non-clear-cell RCC patients at varying risk of recurrence and survival.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Estudos Retrospectivos , Prognóstico , Nefrectomia
3.
Mol Psychiatry ; 29(2): 439-448, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38114630

RESUMO

The adverse psychological and social impacts of COVID-19 pandemic are well characterized, but the role of composite, modifiable lifestyle factors that may interact to mitigate these impacts is not. The effect of socioeconomic deprivation on these lifestyle risks also remains unclear. Based on a nationally representative, longitudinal cohort, we assessed the association between a combination of pre-pandemic lifestyle factors and mental health conditions during pandemic, and the contribution of deprivation to it. Composite lifestyle factors included BMI, smoking status, alcohol consumption, physical activity, sedentary time, sleep duration, and fruit and vegetable intake, with lifestyle scores and lifestyle categories calculated for each participant. Symptoms of depression and anxiety, and personal well-being were assessed by validated scales during the pandemic. Socioeconomic deprivation was characterized by both individual-level (income, wealth, and education) and group-level factors (Index of Multiple Deprivation). Of the 5049 eligible participants (mean [SD] age, 68.1 [10.9] years; 57.2% were female) included in the study, 41.6% followed a favorable lifestyle, 48.9% followed an intermediate lifestyle, and 9.5% followed an unfavorable lifestyle. Compared with favorable lifestyle category, participants in the intermediate and unfavorable lifestyle category were at increased risk of mental health conditions, with the hazard ratio (HR) for trend per increment change towards unfavorable category of 1.17 (95% CI 1.09-1.26) for depression, 1.23 (1.07-1.42) for anxiety, and 1.39 (1.20-1.61) for low well-being. A significant trend of lower risk for mental health conditions with increasing number of healthy lifestyle factors was observed (P < 0.001 for trend). There were no significant interactions between lifestyle factors and socioeconomic deprivation for any of the outcomes, with similar HRs for trend per one increment change in lifestyle category observed in each deprivation group. Compared with those in the least deprived group with favorable lifestyle, participants in the most deprived group adherent to unfavorable lifestyle had the highest risk of mental health outcomes. These results suggest that adherence to a broad combination of healthy lifestyle factors was associated with a significantly reduced risk of mental health conditions during the COVID-19 pandemic. Lifestyle factors, in conjunction with socioeconomic deprivation, independently contribute to the risk of mental health issues. Although further research is needed to assess causality, the current findings support public health strategies and individual-level interventions that provide enhanced support in areas of deprivation and target multiple lifestyle factors to reduce health inequalities and promote mental well-being during the ongoing COVID-19 pandemic.


Assuntos
Ansiedade , COVID-19 , Depressão , Estilo de Vida Saudável , Saúde Mental , Pandemias , Fatores Socioeconômicos , Humanos , COVID-19/epidemiologia , COVID-19/psicologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Depressão/epidemiologia , Ansiedade/epidemiologia , Exercício Físico/psicologia , Estudos Longitudinais , Estilo de Vida , SARS-CoV-2 , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/psicologia , Fumar/epidemiologia , Fumar/psicologia
4.
Cancers (Basel) ; 15(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36672425

RESUMO

BACKGROUND: China has the highest number of new cancer cases and deaths worldwide, posing huge health and economic burdens to society and affected families. This study comprehensively analyzed secular trends of national cancer mortality statistics to inform future prevention and intervention programs in China. METHODS: The annual estimate of overall cancer mortality and its major subtypes were derived from the National Health Commission (NHC). Joinpoint analysis was used to detect changes in trends, and we used age-period-cohort modeling to estimate cohort and period effects in Cancers between 1987 and 2020. Net drift (overall annual percentage change), local drift (annual percentage change in each age group), longitudinal age curves (expected longitudinal age-specific rate), and period (cohort) relative risks were calculated. RESULTS: The age-standardized cancer mortality in urban China has shown a steady downward trend but has not decreased significantly in rural areas. Almost all cancer deaths in urban areas have shown a downward trend, except for colorectal cancer in men. Decreasing mortality from cancers in rural of the stomach, esophagus, liver, leukemia, and nasopharynx was observed, while lung, colorectal cancer female breast, and cervical cancer mortality increased. Birth cohort risks peaked in the cohorts born around 1920-1930 and tended to decline in successive cohorts for most cancers except for leukemia, lung cancer in rural, and breast and cervical cancer in females, whose relative risks were rising in the very recent cohorts. In addition, mortality rates for almost all types of cancer in older Chinese show an upward trend. CONCLUSIONS: Although the age-standardized overall cancer mortality rate has declined, and the urban-rural gap narrowed, the absolute cancer cases kept increasing due to the growing elderly population in China. The rising mortality related to lung, colorectal, female breast, and cervical cancer should receive higher priority in managing cancer burden and calls for targeted public health actions to reverse the trend.

5.
J Am Med Dir Assoc ; 24(2): 206-212.e5, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36370750

RESUMO

OBJECTIVES: This study aimed to reveal the epidemic characteristics of chronic diseases among the Chinese older population and provide empirical strategies for the prevention and management of chronic diseases in the seniors in China. DESIGN: A national cross-sectional study. SETTING AND PARTICIPANTS: A total of 224,640 Chinese residents aged 60 and older were invited, and 222,179 (98.9%) participated in our survey. METHODS: Standardized questionnaires were used to collect socioeconomic information and self-reported physician-diagnosed chronic diseases. The associations between individual socioeconomic status and chronic diseases were estimated using generalized linear mixed-effects models. RESULTS: The national prevalence of any chronic diseases was 81.1% (95% CI 80.9-81.2), representing 179.9 million Chinese older adults. The prevalence increased with aging and peaked at 80 to 84 years old (87.2, 95% CI 86.7-87.7), this is consistent with studies in developing countries. Women (84.2, 84.0-84.4), rural residents (82.6, 82.4-82.8), and ethnic minorities (82.2, 81.5-82.8) had a higher prevalence than men (77.7, 77.4-77.9), urban residents (79.7, 79.5-79.9), and people of Han ethnicity (81.0, 80.8-81.2), respectively. For provincial prevalence, Tibet had the highest prevalence of chronic diseases (91.8, 91.5-92.0), and Fujian had the lowest (72.7, 72.5-72.9). The absolute differences between the highest and lowest provinces for the specific chronic condition ranged from 2.78% for cancer to 36.3% for cardiovascular diseases. CONCLUSIONS AND IMPLICATIONS: Chronic diseases were highly prevalent among older adults in China and varied geographically. Advanced socioeconomic status appeared to have double-edged impacts on the prevalence of chronic diseases. Our findings support that reducing gender and geographic disparities should be prioritized in China's chronic disease prevention and management, and an affordable long-term care services system for older adults should be established urgently in China.


Assuntos
Classe Social , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Fatores Socioeconômicos , China/epidemiologia , Doença Crônica , Prevalência
6.
Acta Ophthalmol ; 100(7): e1479-e1488, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35396902

RESUMO

PURPOSE: To investigate the association between cigarette smoking and retinal capillary plexus (RCP) using optical coherence tomography angiography (OCTA) and to examine whether potential vascular risk factors could impact their association. METHODS: This is a cross-sectional, community-based study. The Jidong Eye Cohort Study included participants aged ≥18 years in the Jidong community (Tangshan city, northern China) from August 2019 to January 2020. All participants underwent comprehensive ophthalmic examination and completed detailed smoking questionnaires. Retinal vessel density in the superficial and deep RCP was automatically measured using OCTA. RESULTS: Of the 2598 participants included in the study, 2026 (78.0%) never smoked and 572 (22.0%) had a history of smoking (494 [19.0%] current smokers and 78 [3.0%] former smokers). The median (interquartile range) age was 41 (34-52) years for the non-smoking group and 45 (35-54.5) years for the smoking group. Multivariable analysis showed that smoking history is associated with a low deep RCP vessel density in the parafovea (ß, -0.53; 95% confidence interval [CI], -0.82 to -0.24) and four quadrants. Increased smoking pack-years were associated with reduced deep RCP vessel density in the parafovea (p for trend <0.001) and four quadrants. The significant interaction between diabetes and smoking only was found for superficial RCP vessel density in the parafovea (p for interaction = 0.014) and four quadrants except for the temporal quadrants. CONCLUSIONS: Cigarette smoking is an independent risk factor for reduced deep RCP vessel density. Our findings imply the potential detrimental effect of smoking on the occurrence of ocular diseases.


Assuntos
Fumar Cigarros , Tomografia de Coerência Óptica , Adolescente , Adulto , Fumar Cigarros/efeitos adversos , Estudos de Coortes , Estudos Transversais , Angiofluoresceinografia/métodos , Humanos , Pessoa de Meia-Idade , Retina , Vasos Retinianos/diagnóstico por imagem , Fumar/efeitos adversos , Tomografia de Coerência Óptica/métodos
7.
Diabetes Metab ; 48(1): 101266, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34252500

RESUMO

AIMS: - Evidence for the effects of metabolically healthy obese (MHO) status on heart failure (HF) is limited and ignores the dynamic change of metabolic health and obesity phenotypes. We aimed to investigate the associations of metabolic health and its transition with HF across body mass index (BMI) and waist circumference (WC) categories. METHODS: - This prospective cohort study was conducted with 93,288 Chinese adults who were free of cardiovascular disease, cancer or HF at baseline (2006-2007). Metabolic health was defined as having no or only one abnormality in blood pressure, glucose, high-density lipoprotein cholesterol, or triglyceride levels. Participants were cross-classified at baseline by metabolic health and obesity (defined by BMI and WC criteria). Transitions in metabolic health status from 2006 to 2007 to 2010 to 2011 were considered. The hazard ratios (HRs) and 95% confidence intervals (CIs) for HF were assessed by Cox proportional hazards regression. RESULTS: - During a mean ± standard deviation follow-up of 9.7 ± 1.5 years, 1,628 participants developed HF. Individuals with MHO (HR: 1.78, 95% CI: 1.45, 2.19 for BMI criteria; HR: 1.51, 95% CI: 1.30, 1.76 for WC criteria) had higher risk of HF than those with metabolically healthy normal weight (MHNW). Individuals with initial MHO who shifted to metabolically unhealthy phenotype during follow-up had higher risk of HF compared with stable MHNW individuals (HR 3.12; 95% CI: 2.01, 4.85 for BMI categories; HR 1.98; 95% CI: 1.42, 2.77 for WC categories). Even stable MHO individuals were at an increased risk of HF compared with stable MHNW individuals (HR: 2.17; 95% CI: 1.39, 3.39 for BMI categories; HR: 1.33; 95% CI: 0.96, 1.85 for WC categories). CONCLUSIONS: - MHO phenotype is dynamic and its transition to metabolically unhealthy phenotype or even stable MHO is associated with increased risk of HF. Maintaining metabolic health may provide a clue for preventing HF.


Assuntos
Insuficiência Cardíaca , Obesidade Metabolicamente Benigna , Índice de Massa Corporal , Nível de Saúde , Insuficiência Cardíaca/epidemiologia , Humanos , Obesidade Metabolicamente Benigna/epidemiologia , Fenótipo , Estudos Prospectivos , Fatores de Risco
8.
Pathol Res Pract ; 215(6): 152379, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30878308

RESUMO

BACKGROUND: Epidemiological studies have illustrated that regular aspirin consumption may decrease the risk of non-small cell lung cancer (NSCLC). The present study aims to investigate the mechanism of aspirin-induced inhibition of NSCLC development during hypoxia. METHODS: A549 cells were pre-treated with the vehicle control or aspirin and then subjected to hypoxic culture. Cell viability was monitored by CCK-8 assay, and flow cytometry was performed to detect cell cycle distributions, apoptosis, and proportion of cancer stem cells (CSCs). Flow cytometric cell sorting was used to separate CSCs. Quantitative reverse transcription-polymerase chain reaction and Western blot were used to detect the mRNA and protein levels of stem cell markers and the related signaling molecules. The abundance of prostaglandin E2 was detected by enzyme-linked immunosorbent assay. Exosomes in the cell culture medium were isolated using ExoQuick, and the number of exosomes was quantified by the EXOCET exosome quantification assay kit. Cell migration and angiogenesis were monitored by transwell migration assay and in vitro angiogenesis experiments. RESULTS: Aspirin inhibited cell proliferation and induced G2/M cell cycle arrest in hypoxic A549 cells; it also inhibited hypoxia-enhanced stemness in both A549 and ALDH+ cells. The drug reduced hypoxia-enhanced numbers of exosomes in A549 cells and exerted negative effects on the hypoxia-mediated up-regulation of exosomal HIF-1α/COX-2 and expression of exosomal miR-135b and miR-210. While hypoxic-induced exosomes can promote the proliferation, migration, and angiogenesis of other A549 cells, aspirin can weaken this promotion by reducing the amount of exosome secreted and changing exosome contents. CONCLUSIONS: Aspirin inhibits the hypoxia-induced stemness, hypoxic-mediated exosome release, and malignant paracrine effects of A549 cells.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Aspirina/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Exossomos/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células A549 , Hipóxia Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos
9.
Zhonghua Yi Xue Za Zhi ; 95(20): 1590-4, 2015 May 26.
Artigo em Chinês | MEDLINE | ID: mdl-26463608

RESUMO

OBJECTIVE: To analyze the characteristics and trends of gastrointestinal mucosal injury for age ≥ 45 years male health care patients during gastro-endoscopic follow-up. METHODS: Endoscopic reports of age ≥ 45 years male health care patients with long-term aspirin undergoing gastroscopy from October 1999 to April 2014 were retrospectively reviewed. The proportion of different lesions, the distribution at different anatomic sites, and the trends of the number of gastrointestinal mucosal injury in different follow up years were analyzed. RESULTS: A total of 2 281 endoscopic reports of 259 health care cases aged ≥ 45 years with aspirin used 3 years at least were collected. After the initial gastroscopy screening, there are 239, 103 and 20 cases followed up to the 5(th), 10(th) and 15(th) years. The patients were between 45-91 years of age, their mean age was 67 years. The mean followed-up time was 5 years. In the follow-up process each patient had 8 gastroscopies performed. A total of 4 442 lesions were detected and the mean number was 2 per person for once. The number of gastrointestinal mucosal injuries were different. The number of the gastrointestinal mucosal injury of the 1(st) year was higher than that of initial gastro-endoscopy (P < 0.05). The numbers of the gastrointestinal mucosal injury of the 2(se)-5(th) years during the follow up period were lower than those of initial gastro-endoscopy (all P < 0.05). The numbers of three different lesions of gastrointestinal mucosal injury were different (P < 0.05). The number of erosion was more than petechia and ulcer (both P < 0.05). The Modified Lanza's Score (MDS) were in descending trend during the follow up period. The numbers of gastrointestinal mucosal injury in different anatomic sites were different in the same follow-up years (all P < 0.05). CONCLUSIONS: The numbers and degree of gastrointestinal mucosal injury for middle aged and aged health care patients with long-term aspirin used during gastro-endoscopic follow-up are in descending trend, however, there is a transient increasing in number of gastrointestinal mucosal injury in the first two years since the aspirin used. The common lesion in gastrointestinal mucosal injury is erosions. Gastric antrum and body are vulnerable anatomical parts during follow-up.


Assuntos
Mucosa Gástrica , Gastroenteropatias , Mucosa Intestinal , Aspirina , Seguimentos , Gastroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
10.
PLoS One ; 9(10): e109459, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25290692

RESUMO

PURPOSE: The aim of this study was to evaluate the relationship between long-term aspirin use with pretreatment 18 Fluorodeoxyglucose (FDG) uptake of primary lesions of Colorectal cancer (CRC) and evaluate their clinical significance. MATERIALS AND METHODS: We enrolled 84 patients with CRC who underwent 18F-FDG PET/CT scanning before surgery between 1st July 2008 and 1st March 2013 and followed up until 1st March 2014. Maximum standardized uptake value (SUVmax) of the primary tumor was measured by 18F-FDG PET/CT. The history of aspirin taken and other clinicopathogical factors were also obtained and their relationships were examined by Mann-Whitney or χ2 tests. Progression-free survival (PFS) was determined by standard Kaplan-Meier survival analysis. Cox proportional hazards regression was performed to determine whether history of aspirin taken, pretreatment SUVmax, age, gender, TNM stage, tumor sizes and differentiation influenced outcomes. RESULTS: CRC Patients with long-term history of aspirin use had lower SUVmax of primary lesions than control group (9.74±2.62 vs. 13.91±6.18) and showed a trend towards improved PFS after curative surgery. However, pretreatment of SUVmax showed no prognostic value in patients with CRC. CONCLUSIONS: Long-term aspirin use is associated with lower pretreatment SUVmax of CRC and is a promising prognostic factor for predicting PFS in patients with CRC.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Fluordesoxiglucose F18/metabolismo , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Prognóstico , Compostos Radiofarmacêuticos/metabolismo , Tomografia Computadorizada por Raios X , Carga Tumoral
11.
World J Gastroenterol ; 19(29): 4702-17, 2013 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-23922467

RESUMO

AIM: To investigate the potential therapeutic effects of mesenchymal stem cells (MSCs) in inflammatory bowel disease (IBD), we transplanted MSCs into an experimental model of IBD. METHODS: A rectal enema of trinitrobenzene sulfonic acid (TNBS) (100 mg/kg body weight) was administered to female BALB/c mice. Bone marrow mesenchymal stem cells (BMSCs) were derived from male green fluorescent protein (GFP) transgenic mice and were transplanted intravenously into the experimental animals after disease onset. Clinical activity scores and histological changes were evaluated. GFP and Sex determining region Y gene (SRY) expression were used for cell tracking. Ki67 positive cells and Lgr5-expressing cells were determined to measure proliferative activity. Inflammatory response was determined by measuring the levels of different inflammatory mediators in the colon and serum. The inflammatory cytokines included tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-6, IL-17, IL-4, IL-10, and transforming growth factor (TGF-ß). Master regulators of Th1 cells (T-box expressed in T cells, T-bet), Th17 cells (retinoid related orphan receptor gamma(t), RORγt), Th2 cells (GATA family of transcription factors 3, GATA3) and regulatory T cells (forkhead box P3, Foxp3) were also determined. RESULTS: Systemic infusion of GFP-BMSCs ameliorated the clinical and histopathologic severity of colitis, including body weight loss, diarrhea and inflammation, and increased survival (P < 0.05). The cell tracking study showed that MSCs homed to the injured colon. MSCs promoted proliferation of intestinal epithelial cells and differentiation of intestinal stem cells (P < 0.01). This therapeutic effect was mainly mediated by down-regulation of both Th1-Th17-driven autoimmune and inflammatory responses (IL-2, TNF-α, IFN-γ, T-bet; IL-6, IL-17, RORγt), and by up-regulation of Th2 activities (IL-4, IL-10, GATA-3) (P < 0.05). MSCs also induced activated CD4(+)CD25(+)Foxp3(+) regulatory T cells (TGF-ß, IL-10, Foxp3) with a suppressive capacity on Th1-Th17 effecter responses and promoted Th2 differentiation in vivo (P < 0.05). CONCLUSION: MSCs are key regulators of immune and inflammatory responses and may be an attractive candidate for cell-based therapy of IBD.


Assuntos
Autoimunidade , Colite/cirurgia , Colo/imunologia , Citocinas/sangue , Mediadores da Inflamação/sangue , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/imunologia , Ácido Trinitrobenzenossulfônico , Animais , Biomarcadores/metabolismo , Diferenciação Celular , Proliferação de Células , Rastreamento de Células , Células Cultivadas , Colite/sangue , Colite/induzido quimicamente , Colite/imunologia , Colite/patologia , Colo/metabolismo , Colo/patologia , Modelos Animais de Doenças , Feminino , Proteínas de Fluorescência Verde/biossíntese , Proteínas de Fluorescência Verde/genética , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Antígeno Ki-67/metabolismo , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Receptores Acoplados a Proteínas G/metabolismo , Linfócitos T Reguladores/imunologia , Células Th2/imunologia , Fatores de Tempo , Cicatrização
12.
Zhonghua Yi Xue Za Zhi ; 93(6): 452-4, 2013 Feb 05.
Artigo em Chinês | MEDLINE | ID: mdl-23660267

RESUMO

OBJECTIVE: To observe the occurrence characteristics, dynamic variations and potential risks of smaller gastrointestinal submucosal tumor (SMT) in elderly patients. METHODS: A total of 54 SMT patients were retrospectively recruited from January 1981 to September 2010. There were 51 males (94.4%) and 3 females (5.6%) with an average age of (74 ± 1) years. During each visit, all the relevant data were collected, including symptoms, number of lesion, lesion location, shape, size (maximum transverse diameter under endoscope or endoscopic ultrasonography (EUS), morphology of mucosa, frequency and duration of follow-ups, treatment and pathological results. And the data were analyzed to examine the characteristics of SMT in elderly patients and their dynamic variations. Further more, according to lesion diameter, they were divided into two groups: a diameter ≤ 1 cm (n = 36) and a diameter > 1 cm and ≤ 3 cm (n = 16). Then the change of two groups were observed and compared during the follow-ups. RESULTS: Two cases were not under surveillance after direct surgical resection. The other 52 patients received a follow-up of 22 years. Among them, 5 patients underwent surgical resection for fast-growing tumor and mucosal ulcer. And all their pathologic diagnoses were malignant. Only 1 patient (2.8%) in the diameter ≤ 1 cm group and 4 in the diameter > 1 cm and ≤ 3 cm group turned malignant at 6 years. But, among 4 patients, the shortest interval was merely 14 months. Therefore, compared with the diameter > 1 cm group, the diameter ≤ 1 cm group had a lower rate of malignancy (P < 0.05). CONCLUSIONS: The incidence of smaller SMT (especially diameter ≤ 1 cm) is high in elderly patients, but the malignant potential remains low. Therefore, for elderly patients whose diameters of SMT are no bigger than 3 cm and without obvious malignancy under endoscope or EUS, we may plan an appropriate surveillance interval based on the size of tumor during a long follow-up period.


Assuntos
Mucosa Gástrica/patologia , Neoplasias Gastrointestinais/patologia , Mucosa Intestinal/patologia , Idoso , Endoscopia , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos
13.
World J Gastroenterol ; 18(17): 2121-6, 2012 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-22563201

RESUMO

AIM: To determine whether serum levels of carcinoembryonic antigen (CEA) correlate with the presence of primary colorectal cancer (CRC), and/or recurrent CRC following radical resection. METHODS: A total of 413 patients with CRC underwent radical surgery between January 1998 and December 2002 in our department and were enrolled in this study. The median follow-up period was 69 mo (range, 3-118 mo), and CRC recurrence was experienced by 90/413 (21.8%) patients. Serum levels of CEA were assayed preoperatively, and using a cutoff value of 5 ng/mL, patients were divided into two groups, those with normal serum CEA levels (e.g., ≤ 5 ng/mL) and those with elevated CEA levels (> 5 ng/mL). RESULTS: The overall sensitivity of CEA for the detection of primary CRC was 37.0%. The sensitivity of CEA according to stage, was 21.4%, 38.9%, and 41.7% for stages I-III, respectively. Moreover, for stage II and stage III cases, the 5-year disease-free survival rates were reduced for patients with elevated preoperative serum CEA levels (P < 0.05). The overall sensitivity of CEA for detecting recurrent CRC was 54.4%, and sensitivity rates of 36.6%, 66.7%, and 75.0% were associated with cases of local recurrence, single metastasis, and multiple metastases, respectively. In patients with normal serum levels of CEA preoperatively, the sensitivity of CEA for detecting recurrence was reduced compared with patients having a history of elevated CEA prior to radical resection (32.6% vs 77.3%, respectively, P < 0.05). CONCLUSION: CRC patients with normal serum CEA levels prior to resection maintained these levels during CRC recurrence, especially in cases of local recurrence vs cases of metastasis.


Assuntos
Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/diagnóstico , Adulto , Idoso , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Sensibilidade e Especificidade
14.
Zhonghua Yi Xue Za Zhi ; 90(46): 3276-8, 2010 Dec 14.
Artigo em Chinês | MEDLINE | ID: mdl-21223786

RESUMO

OBJECTIVE: To investigate the prognostic and relapsing factors of ulcerative colitis by a 5-year population-based follow-up. METHODS: A total of 525 patients diagnosed with ulcerative colitis during the period from 1994 to 2005 at our hospital were recruited and followed prospectively for 5 years or until a relapse. The evaluation at 5 years included interview, clinical examination, laboratory tests and colonoscopy. RESULTS: Among these patients, 367 patients suffered from a relapse of ulcerative colitis with a median age of 42 years old. And 263 (50.1%) patients took part in the follow-up study. The median duration of maintenance treatment was (16.3±3.9) months. The proportion of relapse was significant greater in females (P<0.05) and in patients over 60 years old versus those under 60 (P<0.05). The value of CRP was unrelated with the relapsing rate (P>0.05). During the follow-up, 36.5% of the patients relapsed within 12 months, 75.3% within 2 years and 87.8% within 5 years. And 61.5% of the patients relapsed after drug withdrawal, 11.3% in maintenance treatment and 27.2% with no treatment. Severity, extent of disease and duration of maintenance treatment showed significant differences between the relapsing group and relapsing-free groups (P<0.05). CONCLUSION: The relapsing factors of ulcerative colitis are gender, age, severity, extent of disease and duration of maintenance treatment.


Assuntos
Colite Ulcerativa , Adulto , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva
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