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1.
J Dig Dis ; 25(2): 109-122, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38503514

RESUMO

OBJECTIVE: We aimed to explore the geographic differences in psychological symptoms, sleep quality, and quality of life (QoL) among adult patients with inflammatory bowel disease (IBD). METHODS: A unified questionnaire was developed to collect data on psychological status and QoL of IBD patients from 42 hospitals across 22 provinces, municipalities, and autonomous regions in China's mainland from September 2021 to May 2022. RESULTS: A total of 2478 patients with IBD were surveyed. The proportions of patients with anxiety (28.5% vs 23.1%), depression (32.3% vs 27.8%), and poor QoL (44.8% vs 32.2%) were significantly higher in patients from the northern region compared to the southern region (all P < 0.05). In the western region, the proportions of patients with anxiety (31.9% vs 23.0%), depression (37.7% vs 26.7%), sleep disturbances (64.5% vs 58.5%), and poor QoL (44.9% vs 34.8%) were significantly higher than in the eastern and central regions (all P < 0.01). Patients from inland regions had significantly higher rates of anxiety (27.1% vs 23.3%), depression (32.5% vs 26.0%), sleep disturbance (62.0% vs 57.7%), and poor QoL (43.5% vs 29.9%) compared to those from coastal regions (all P < 0.05). In economically underdeveloped areas, the proportions of patients with depression (33.1% vs 28.5%) and poor QoL (52.0% vs 32.4%) were significantly higher than in economically (relatively) developed areas (both P < 0.05). CONCLUSION: There are significant geographic differences in psychological symptoms, sleep quality, and QoL among Chinese patients with IBD, which might provide valuable insights for global IBD research and clinical practice.


Assuntos
Doenças Inflamatórias Intestinais , Qualidade de Vida , Adulto , Humanos , Qualidade de Vida/psicologia , Qualidade do Sono , Depressão/epidemiologia , Depressão/etiologia , Depressão/psicologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/psicologia , Ansiedade/epidemiologia , Ansiedade/etiologia , Ansiedade/psicologia , China/epidemiologia
2.
J Dig Dis ; 24(10): 504-515, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37796223

RESUMO

OBJECTIVES: Risk of cerebrovascular accidents (CVAs) in patients with inflammatory bowel disease (IBD) remains inconclusive. In this systematic review and meta-analysis, we aimed to estimate the incidence of and identify the risk factors for CVA in patients with IBD. METHODS: PubMed, EMBASE and Web of Science were searched for articles published up to January 13, 2023 to identify those reported the incidence of CVA in IBD patients, along with the total person-years or related data to calculate it. The main outcomes were the incidence of and risk factors for CVA in IBD. RESULTS: Based on the analysis of 10 studies, the pooled incidence of CVA in IBD patients was 2.74 per 1000 person-years (95% confidence interval [CI] 1.83-4.10 person-years; I2 = 99.2%), which was higher than that in the general population (incidence rate ratio [IRR] 1.21, 95% CI 1.09-1.34, P = 0.0002; I2 = 84.8%). Risk factors for CVA in IBD patients were age (significance in different definitions), ulcerative colitis (IRR 1.214, 95% CI 1.000-1.474, P = 0.0499; I2 = 81.9%), disease flares (IRR 1.699, 95% CI 1.359-2.122, P < 0.0001; I2 = 28.7%) and chronic activity (IRR 2.202, 95% CI 1.378-3.519, P = 0.0010; I2 = 83.0%). CONCLUSIONS: The risk of CVA modestly increased in IBD patients. Both the traditional and IBD-related risk factors should be managed to prevent CVA in these patients. Since the effects of risk factors were derived from pooled results of only 2-3 studies, further research is needed to confirm our results.


Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Acidente Vascular Cerebral , Humanos , Incidência , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Colite Ulcerativa/complicações , Colite Ulcerativa/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Fatores de Risco
3.
World J Pediatr ; 19(10): 939-948, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37022658

RESUMO

BACKGROUND: Good quality of care for inflammatory bowel disease (IBD) depends on high-standard management and facility in the IBD center. Yet, there are no clear measures or criteria for evaluating pediatric IBD (PIBD) center in China. The aim of this study was to develop a comprehensive set of quality indicators (QIs) for evaluating PIBD center in China. METHODS: A modified Delphi consensus-based approach was used to identify a set of QIs of structure, process, and outcomes for defining the criteria. The process included an exhaustive search using complementary approaches to identify potential QIs, and two web-based voting rounds to select the QIs defining the criteria for PIBD center. RESULTS: A total of 101 QIs (35 structures, 48 processes and 18 outcomes) were included in this consensus. Structure QIs focused on the composition of multidisciplinary team, facilities and services that PIBD center should provide. Process QIs highlight core requirements in diagnosing, evaluating, treating PIBD, and disease follow-up. Outcome QIs mainly included criteria evaluating effectiveness of various interventions in PIBD centers. CONCLUSION: The present Delphi consensus developed a set of main QIs that may be useful for managing a PIBD center. Video Abstract.


Assuntos
Doenças Inflamatórias Intestinais , Humanos , Criança , Consenso , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/terapia , China
4.
Gut ; 71(2): 238-253, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34836916

RESUMO

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.


Assuntos
Saúde da Família , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori , Controle de Infecções/organização & administração , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , China , Consenso , Técnica Delphi , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/transmissão , Humanos , Lactente , Pessoa de Meia-Idade , Adulto Jovem
6.
Front Med (Lausanne) ; 8: 621337, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33996846

RESUMO

Background and Aim: Serum immunoglobulins were reported to be associated with clinical characteristics of inflammatory bowel disease. However, whether a difference exists in the serum immunoglobulins levels in patients with Crohn's disease (CD) with different disease location and behavior phenotypes remains unclear. Therefore, this study aimed to explore the associations of serum immunoglobulins levels with specific CD phenotypes. Methods: Patients with CD having recorded serum immunoglobulins levels were recruited through multicenter collaborative efforts. The associations between serum immunoglobulins levels and distinct phenotypes of CD were evaluated using multiple logistic regression models. Results: A total of 608 patients with CD were included in the study. Elevated (above the upper limit of normal) serum immunoglobulin G (IgG), IgA, IgM, and IgG4 were identified in 24.5, 17.4, 2.1, and 8.2% of patients, respectively. Elevated serum IgG4 levels negatively correlated with complicated disease behavior [odds ratio (OR) 0.49, 95% confidence interval (CI) 0.26-0.92]. Elevated serum IgG was linked to isolated ileal disease with an OR of 0.37 (95% CI 0.23-0.61). The ORs of isolated ileal disease progressively reduced across increasing quartiles of IgG (P for trend < 0.001). The adjusted ORs of isolated ileal disease for increasing quartiles of IgM were 1.82 (1.07-3.1), 1.92 (1.14-3.24), 1.17 (0.69-1.98), and 1 (P for trend = 0.008). Besides, serum IgA and IgG levels significantly correlated with several disease activity indices. Conclusions: These results suggested that certain serum immunoglobulins were associated with specific disease phenotypes of CD. Further investigations to account for the associations are warranted.

7.
Gastroenterol Rep (Oxf) ; 9(1): 14-21, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33747522

RESUMO

BACKGROUND: Data from single-center experience or small sample-sized studies have shown that chromoendoscopy (CE) might be superior to white-light endoscopy (WLE) for dysplasia surveillance in ulcerative colitis (UC) patients. We performed a prospective randomized trial with a long-term follow-up to compare the detection rate of dysplasia among WLE with targeted biopsies (WLT), WLE with random biopsies (WLR), and dye-based CE with targeted biopsies (CET) in UC patients. METHODS: Patients with long-standing UC were enrolled from 11 medical centers from March 2012 to December 2013 and randomized into three arms (WLT, WLR, and CET). Only high-definition endoscopy was used in all three groups. The patients were followed up by annual endoscopy with biopsies through December 2017. RESULTS: With a median follow-up time of 55 months, a total of 122 patients with 447 colonoscopies were finally analysed in the per-protocol set: WLT (n = 43), WLR (n = 40), and CET (n = 39). A total of 34 dysplastic lesions were found in 29 colonoscopies of 21 patients. WLR and CET could identify more colonoscopies that diagnosed dysplasia than WLT (8.1% and 9.7% vs 1.9%; P = 0.014 and 0.004, respectively). WLR obtained more biopsied samples than WLT and CET (16.4 ± 5.1 vs 4.3 ± 1.4 and 4.3 ± 1.4; both P < 0.001). During the second half of the follow-up (37 - 69 months), CET could identify more colonoscopies that diagnosed dysplasia than WLT (13.3% vs 1.6%, P = 0.015) and showed a trend for increasing the detection rate compared with WLR (13.3% vs 4.9%, P = 0.107). CONCLUSIONS: For a better outcome of cancer/dysplasia surveillance in patients with long-standing UC, CET appeared to be more effective than WLT and less tedious than WLR. CET was found to be particularly useful when a long-term (>3 years) follow-up was conducted for dysplasia surveillance. The trial was registered on www.chictr.org.cn (ChiCTR1900023689).

8.
Clin Gastroenterol Hepatol ; 19(1): 119-127.e1, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-31923642

RESUMO

BACKGROUND & AIMS: Patients found to be at high risk of advanced proximal neoplasia (APN) after flexible sigmoidoscopy screening should be considered for colonoscopy examination. We developed and validated a scoring system to identify persons at risk for APN. METHODS: We collected data from 7954 asymptomatic subjects (age, 50-75 y) who received screening colonoscopy examinations at 14 sites in Asia. We randomly assigned 5303 subjects to the derivation cohort and the remaining 2651 to the validation cohort. We collected data from the derivation cohort on age, sex, family history of colorectal cancer, smoking, drinking, body mass index, medical conditions, and use of nonsteroidal anti-inflammatory drugs or aspirin. Associations between the colonoscopic findings of APN and each risk factor were examined using the Pearson χ2 test, and we assigned each participant a risk score (0-15), with scores of 0 to 3 as average risk and scores of 4 or higher as high risk. The scoring system was tested in the validation cohort. We used the Cochran-Armitage test of trend to compare the prevalence of APN among subjects in each group. RESULTS: In the validation cohort, 79.5% of patients were classified as average risk and 20.5% were classified as high risk. The prevalence of APN in the average-risk group was 1.9% and in the high-risk group was 9.4% (adjusted relative risk, 5.08; 95% CI, 3.38-7.62; P < .001). The score included age (61-70 y, 3; ≥70 y, 4), smoking habits (current/past, 2), family history of colorectal cancer (present in a first-degree relative, 2), and the presence of neoplasia in the distal colorectum (nonadvanced adenoma 5-9 mm, 2; advanced neoplasia, 7). The c-statistic of the score was 0.74 (95% CI, 0.68-0.79), and for distal findings alone was 0.67 (95% CI, 0.60-0.74). The Hosmer-Lemeshow goodness-of-fit test statistic was greater than 0.05, indicating the reliability of the validation set. The number needed to refer was 11 (95% CI, 10-13), and the number needed to screen was 15 (95% CI, 12-17). CONCLUSIONS: We developed and validated a scoring system to identify persons at risk for APN. Screening participants who undergo flexible sigmoidoscopy screening with a score of 4 points or higher should undergo colonoscopy evaluation.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Idoso , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco
9.
J Dig Dis ; 21(11): 621-628, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32909356

RESUMO

OBJECTIVE: We aimed to evaluate the short-term efficacy and safety of fecal microbiota transplantation (FMT) by washed preparation for moderate to severely active UC. METHODS: An open-label prospective trial was conducted in an inflammatory bowel disease (IBD) tertiary referral center from April 2016 to March 2018. Patients with moderate to severely active UC were randomly assigned to undergo FMT thrice on day 1, 3 and 5 by nasojejunal tube (NJT) or transendoscopic enteral tubing (TET). The primary end-point was a clinical response at week 2 post-FMT. The secondary end-points were clinical and endoscopic remission at week 12 post-FMT, safety and disease progression. RESULTS: Of the nine patients included, 77.8% (7/9) achieved a clinical response at week 2. And 55.6% (5/9) and 33.3% (3/9), respectively, achieved clinical remission and endoscopic remission at week 12. In two patients who had no response to FMT, one switched to anti-tumor necrosis factor-α therapy, and the other underwent a colectomy. FMT was delivered through NJT in 44.4% (4/9) of the patients, while TET was used in 55.6% (5/9). The clinical outcomes did not differ significantly based on the delivery route (P > 0.05). Adverse events, all mild and self-limiting, were observed in 33.3% (3/9) of the patients. CONCLUSIONS: FMT by washed preparation appears to be a safe and effective adjunct therapy for moderate to severely active UC during a short-term follow-up. The efficacy did not differ significantly between the NJT or TET delivery routes. Further randomized controlled studies are needed to confirm these findings.


Assuntos
Colite Ulcerativa , Transplante de Microbiota Fecal , Adulto , Colite Ulcerativa/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão , Resultado do Tratamento
10.
JGH Open ; 4(3): 320-323, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32514431

RESUMO

The COVID-19 pandemic, secondary to SARS-CoV-2, has resulted in high mortality and morbidity worldwide. As inflammatory bowel disease (IBD) is a chronic disease, and most patients are on long-term immunosuppressive agents, there is understandable concern, particularly in terms of therapy. In view of this, experts in IBD across the Asia Pacific region were invited to put together recommendations based on their experience and the currently available data. In general, most IBD therapies (with a few exceptions) can be continued safely, and the general consensus is that maintaining disease control should remain the main principle of management. In addition, social distancing measures and the appropriate use of personal protective equipment should be strictly adhered to. During the current pandemic, face-to-face clinic follow ups and non-urgent procedures should be kept to a minimum.

11.
J Clin Invest ; 130(8): 4301-4319, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32396532

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers and is highly resistant to current treatments. ESCC harbors a subpopulation of cells exhibiting cancer stem-like cell (CSC) properties that contribute to therapeutic resistance including radioresistance, but the molecular mechanisms in ESCC CSCs are currently unknown. Here, we report that ribosomal S6 protein kinase 4 (RSK4) plays a pivotal role in promoting CSC properties and radioresistance in ESCC. RSK4 was highly expressed in ESCC CSCs and associated with radioresistance and poor survival in patients with ESCC. RSK4 was found to be a direct downstream transcriptional target of ΔNp63α, the main p63 isoform, which is frequently amplified in ESCC. RSK4 activated the ß-catenin signaling pathway through direct phosphorylation of GSK-3ß at Ser9. Pharmacologic inhibition of RSK4 effectively reduced CSC properties and improved radiosensitivity in both nude mouse and patient-derived xenograft models. Collectively, our results strongly suggest that the ΔNp63α/RSK4/GSK-3ß axis plays a key role in driving CSC properties and radioresistance in ESCC, indicating that RSK4 is a promising therapeutic target for ESCC treatment.


Assuntos
Neoplasias Esofágicas/enzimologia , Carcinoma de Células Escamosas do Esôfago/enzimologia , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/biossíntese , Tolerância a Radiação , Proteínas Quinases S6 Ribossômicas 90-kDa/biossíntese , Transdução de Sinais , Animais , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/terapia , Células HEK293 , Humanos , Camundongos , Proteínas de Neoplasias/genética , Proteínas Quinases S6 Ribossômicas 90-kDa/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
14.
J Dig Dis ; 20(4): 206-214, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30756472

RESUMO

OBJECTIVE: To compare chromoendoscopy (CE) and white light endoscopy (WLE) for dysplasia surveillance in patients with inflammatory bowel disease (IBD). METHODS: We conducted a meta-analysis of 6 randomized controlled trials (RCTs) and 5 prospective studies and compared the CE and WLE groups. A fixed-effect model was used unless the heterogeneity was high. RESULTS: CE detected more patients with dysplasia (relative risk [RR] 2.05, 95% confidence interval [CI]: 1.62-2.61) and more dysplastic lesions (RR 2.04, 95% CI: 1.40-2.98) than WLE. When magnification was added to CE, the detection rate of patients with dysplasia and dysplastic lesions improved. CE also detected more patients with dysplasia than high-definition WLE (RR 1.60, 95% CI: 1.11-2.29). Compared with WLE, the incremental yield of CE for detecting patients with dysplasia was 9%. CE was superior to WLE in detecting non-polypoid dysplastic lesions (RR 1.38, 95% CI:1.02-1.88). CE had no advantage for detecting polypoid dysplastic lesions compared with WLE. CONCLUSIONS: CE is superior to WLE in the surveillance of dysplasia in IBD patients. It is thus necessary to use CE in the surveillance of dysplasia in patients with IBD in clinical practice. Adding magnification improves the detection rate.


Assuntos
Endoscopia Gastrointestinal/métodos , Doenças Inflamatórias Intestinais/diagnóstico , Mucosa Intestinal/patologia , Humanos , Viés de Publicação
15.
Gut ; 68(5): 796-803, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-29802172

RESUMO

OBJECTIVES: In the management of patients with bleeding peptic ulcers, recurrent bleeding is associated with high mortality. We investigated if added angiographic embolisation after endoscopic haemostasis to high-risk ulcers could reduce recurrent bleeding. DESIGN: After endoscopic haemostasis to their bleeding gastroduodenal ulcers, we randomised patients with at least one of these criteria (ulcers≥20 mm in size, spurting bleeding, hypotensive shock or haemoglobin<9 g/dL) to receive added angiographic embolisation or standard treatment. Our primary endpoint was recurrent bleeding within 30 days. RESULTS: Between January 2010 and July 2014, 241 patients were randomised (added angiographic embolisation n=118, standard treatment n=123); 22 of 118 patients (18.6%) randomised to angiography did not receive embolisation. In an intention-to-treat analysis, 12 (10.2%) in the embolisation and 14 (11.4%) in the standard treatment group reached the primary endpoint (HR 1.14, 95% CI 0.53 to 2.46; p=0.745). The rate of reinterventions (13 vs 17; p=0.510) and deaths (3 vs 5, p=0.519) were similar. In a per-protocol analysis, 6 of 96 (6.2%) rebled after embolisation compared with 14 of 123 (11.4%) in the standard treatment group (HR 1.89, 95% CI 0.73 to 4.92; p=0.192). None of 96 patients died after embolisation compared with 5 (4.1%) deaths in the standard treatment group (p=0.108). In a posthoc analysis, embolisation reduced recurrent bleeding only in patients with ulcers≥15 mm in size (2 (4.5%) vs 12 (23.1%); p=0.027). CONCLUSIONS: After endoscopic haemostasis, added embolisation does not reduce recurrent bleeding. TRIAL REGISTRATION NUMBER: NCT01142180.


Assuntos
Angiografia , Embolização Terapêutica/métodos , Hemostase Endoscópica , Úlcera Péptica Hemorrágica/terapia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Recidiva , Resultado do Tratamento
16.
Biomaterials ; 178: 170-182, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29935385

RESUMO

As HER2 is frequently overexpressed in various malignancies, targeting HER2 is considered an efficient, highly selective antitumor therapy. HER2-targeted immunoconjugates are being developed and result in persistent remission of HER2-overexpressing tumors. However, many of the antibodies used as the targeting moiety are of murine origin and exhibit risk of inducing immunogenicity, limiting their antitumor therapeutic efficacy. Here, we humanized e23sFv, an HER2-targeting murine scFv with excellent affinity and specificity, using a human antibody consensus sequence engraftment strategy. The affinity of the initially humanized e23sFv was then rescued and improved by selective mutagenesis followed by phage-display-based affinity panning of the mutant pool. The resulting humanized e23sFv candidates (husFvs) exhibited up-to-94-fold increased affinity to recombinant HER2. The immunogenicity of e23sFv was dramatically alleviated after humanization, as indicated by the impaired production of cytokines by husFv-stimulated human PBMCs. Two internalizable husFvs with optimal affinity were applied to generate humanized immunoapoptotins by infusion with the translocation domain Fdt and the proapoptotic domain truncated Bid. The husFv-immunoapoptotins demonstrated improved HER2-targeting and tumor-killing capacities in vitro and in vivo compared with the e23sFv-immunoapoptotins and would enable the administration of multiple treatment cycles to patients, resulting in improved antitumor efficacy. Furthermore, the husFvs recognized distinct HER2 epitopes and could thus be used in combination with trastuzumab or pertuzumab to achieve robust synergistic antitumor effects in HER2-positive malignancies.


Assuntos
Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/metabolismo , Fragmentos de Imunoglobulinas/metabolismo , Neoplasias/patologia , Receptor ErbB-2/imunologia , Anticorpos de Cadeia Única/metabolismo , Animais , Linhagem Celular Tumoral , Técnicas de Visualização da Superfície Celular , Citocinas/metabolismo , Citotoxicidade Imunológica , Endocitose , Humanos , Fragmentos de Imunoglobulinas/química , Cinética , Leucócitos Mononucleares/metabolismo , Camundongos Endogâmicos NOD , Camundongos SCID , Mutação/genética , Reprodutibilidade dos Testes , Anticorpos de Cadeia Única/química
17.
Biochem Biophys Res Commun ; 500(4): 924-929, 2018 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-29705704

RESUMO

The transcription factor Forkhead box protein M1 (FOXM1) plays critical roles in cancer development and progression, including human hepatocellular carcinoma (HCC). However, the regulatory role and underlying mechanisms of FOXM1 is still limited. Here, we found that the high level expression of FOXM1 and CCNB1 is closely associated with poor prognosis in HCC patients. And FOXM1 and CCNB1 were overexpressed concomitantly in liver tumor tissues. Knockdown of FOXM1 significantly inhibited the expression levels of CCNB1 in HCC cell lines at both the mRNA and protein levels. Mechanistic studies revealed that FOXM1 binds directly to the promoter region of CCNB1 and regulates the expression levels of the CCNB1 gene in the transcriptional level. Furthermore, the loss of functional and rescue experiments showed that CCNB1 is essential for FOXM1-driven proliferation in HCC cells. In the present study, our results partially explained the dysregulated expression of FOXM1 play an important role in proliferation of human hepatocellular carcinoma cells via transcriptional activation of CCNB1 expression. And it also highlights a FOXM1/CCNB1 axis could be a potential target for the treatment of HCCs.


Assuntos
Carcinoma Hepatocelular/genética , Ciclina B1/genética , Proteína Forkhead Box M1/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , RNA Mensageiro/genética , Sítios de Ligação , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Linhagem Celular Tumoral , Ciclina B1/antagonistas & inibidores , Ciclina B1/metabolismo , Proteína Forkhead Box M1/metabolismo , Células Hep G2 , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Prognóstico , Regiões Promotoras Genéticas , Ligação Proteica , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Análise de Sobrevida , Ativação Transcricional
18.
Gut ; 67(10): 1757-1768, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29691276

RESUMO

Non-variceal upper gastrointestinal bleeding remains an important emergency condition, leading to significant morbidity and mortality. As endoscopic therapy is the 'gold standard' of management, treatment of these patients can be considered in three stages: pre-endoscopic treatment, endoscopic haemostasis and post-endoscopic management. Since publication of the Asia-Pacific consensus on non-variceal upper gastrointestinal bleeding (NVUGIB) 7 years ago, there have been significant advancements in the clinical management of patients in all three stages. These include pre-endoscopy risk stratification scores, blood and platelet transfusion, use of proton pump inhibitors; during endoscopy new haemostasis techniques (haemostatic powder spray and over-the-scope clips); and post-endoscopy management by second-look endoscopy and medication strategies. Emerging techniques, including capsule endoscopy and Doppler endoscopic probe in assessing adequacy of endoscopic therapy, and the pre-emptive use of angiographic embolisation, are attracting new attention. An emerging problem is the increasing use of dual antiplatelet agents and direct oral anticoagulants in patients with cardiac and cerebrovascular diseases. Guidelines on the discontinuation and then resumption of these agents in patients presenting with NVUGIB are very much needed. The Asia-Pacific Working Group examined recent evidence and recommends practical management guidelines in this updated consensus statement.


Assuntos
Embolização Terapêutica/métodos , Endoscopia Gastrointestinal/métodos , Hemorragia Gastrointestinal , Úlcera Péptica Hemorrágica , Inibidores da Agregação Plaquetária/uso terapêutico , Guias de Prática Clínica como Assunto , Inibidores da Bomba de Prótons/uso terapêutico , Consenso , Hemorragia Gastrointestinal/classificação , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/terapia , Humanos , Seleção de Pacientes , Úlcera Péptica Hemorrágica/diagnóstico , Úlcera Péptica Hemorrágica/terapia , Recidiva , Reoperação , Medição de Risco/métodos
19.
Mol Immunol ; 93: 166-172, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29195141

RESUMO

Inflammatory bowel disease (IBD) is caused by aberrant immune responses to the gut microbiota. Among the gut microbiota, adherent-invasive Escherichia Coli (AIEC) is thought to be the pathogen through invading the intestinal epithelial cells and causing inflammation. IL-17 secretion increase, induced by enhanced bacterial adhesion to the intestine epithelium, could on one hand protect the mucosa, but on the other hand, over amount of IL-17 initializes inflammation reactions that in turn damages the mucosa. The relationship between IL-17 and AIEC is still unclear. In this study, we tried to elucidate the function of IL-17 in AIEC-mediated colitis. Wild type (WT) and IL-17 knockout (IL-17 KO) mice were inoculated with AIEC strain E. coli LF82 and treated with dextran sodium sulphate (DSS). Histological examination of the colon was performed. Mucosa damage was assessed and scored. IL-22 and IL-17 in colon tissues were detected by ELISA, qPCR and immunohistochemistry methods. Transient AIEC colonization in IL-17 KO mice resulted in increased intestinal epithelial damage, systemic bacterial burden and mortality compared with WT controls. Moreover, IL-17 is required for the induction of IL-22 in the experimental animal models during AIEC strain E. coli LF82 colonization. These results indicate IL-17 plays a protective role in AIEC strain E. coli LF82 induced colitis by promoting IL-22 secretion.


Assuntos
Colite/imunologia , Escherichia coli Enteropatogênica/imunologia , Infecções por Escherichia coli/imunologia , Interleucina-17/fisiologia , Animais , Aderência Bacteriana , Colite/induzido quimicamente , Colite/microbiologia , Colite/patologia , DNA Bacteriano/genética , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Escherichia coli Enteropatogênica/patogenicidade , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Doenças Inflamatórias Intestinais , Interleucina-17/biossíntese , Interleucina-17/deficiência , Interleucina-17/genética , Interleucinas/biossíntese , Interleucinas/genética , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Camundongos , Camundongos Knockout , Interleucina 22
20.
J Dig Dis ; 17(9): 600-609, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27534592

RESUMO

OBJECTIVE: To establish the colonic expression quantitative trait locus map in Han Chinese population and provide a functional reference for interpreting genetic associations of diseases such as inflammatory bowel disease (IBD). METHODS: Colonic mucosal biopsies and peripheral blood samples were obtained from 48 Chinese Han individuals (24 ulcerative colitis patients and 24 healthy controls). Transcription profiling was performed using human whole genome expression array. Genotyping was done using a population-specific genotype array. Imputation was performed using IMPUTE2. Association between genotypes and gene expression was analyzed using a Matrix Expression Quantitative Trait Loci (eQTL) R package to identify eQTL. We used ChIPpeakAnno R package for annotation of the eQTL. Linkage disequilibrium between the eQTL and IBD risk loci was also investigated. RESULTS: We identified 6 377 single nucleotide polymorphism-transcript interactions (cis-eQTL) in the colon of the Chinese participants. Most of the eQTL located near the transcription starting sites and overlapped with histone modification marks on the genome. A significant proportion of the eQTL were found to be within transcription factor-binding sites. Two IBD risk loci were found to be colon cis-eQTL in Chinese individuals, and 51 cis-eQTL were identified in another 18 IBD risk loci. CONCLUSIONS: This study defined a population-specific catalogue of colon eQTL in the Chinese population. Potential functional variants of IBD association signals were identified. We provided a useful reference dataset for fine mapping IBD risk loci and identifying causal variants in the Chinese Han population.


Assuntos
Colite Ulcerativa/genética , Colo/metabolismo , Locos de Características Quantitativas , Estudos de Casos e Controles , Colite Ulcerativa/metabolismo , Perfilação da Expressão Gênica/métodos , Frequência do Gene , Ontologia Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Código das Histonas/genética , Humanos , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único , Transcrição Gênica
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