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1.
Circ Res ; 131(9): 768-787, 2022 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-36134578

RESUMO

RATIONALE: Vascular smooth muscle cells (VSMCs) phenotype switch from contractile to proliferative phenotype is a pathological hallmark in various cardiovascular diseases. Recently, a subset of long noncoding RNAs was identified to produce functional polypeptides. However, the functional impact and regulatory mechanisms of long noncoding RNAs in VSMCs phenotype switching remain to be fully elucidated. OBJECTIVES: To illustrate the biological function and mechanism of a VSMC-enriched long noncoding RNA and its encoded peptide in VSMC phenotype switching and vascular remodeling. RESULTS: We identified a VSMC-enriched transcript encoded by a previously uncharacterized gene, which we called phenotype switching regulator (PSR), which was markedly upregulated during vascular remodeling. Although PSR was annotated as a long noncoding RNA, we demonstrated that the lncPSR (PSR transcript) also encoded a protein, which we named arteridin. In VSMCs, both arteridin and lncPSR were necessary and sufficient to induce phenotype switching. Mechanistically, arteridin and lncPSR regulate downstream genes by directly interacting with a transcription factor YBX1 (Y-box binding protein 1) and modulating its nuclear translocation and chromatin targeting. Intriguingly, the PSR transcription was also robustly induced by arteridin. More importantly, the loss of PSR gene or arteridin protein significantly attenuated the vascular remodeling induced by carotid arterial injury. In addition, VSMC-specific inhibition of lncPSR using adeno-associated virus attenuated Ang II (angiotensin II)-induced hypertensive vascular remodeling. CONCLUSIONS: PSR is a VSMC-enriched gene, and its transcript IncPSR and encoded protein (arteridin) coordinately regulate transcriptional reprogramming through a shared interacting partner, YBX1. This is a previously uncharacterized regulatory circuit in VSMC phenotype switching during vascular remodeling, with lncPSR/arteridin as potential therapeutic targets for the treatment of VSMC phenotype switching-related vascular remodeling.


Assuntos
RNA Longo não Codificante , Angiotensina II/metabolismo , Proliferação de Células/genética , Células Cultivadas , Cromatina/metabolismo , Humanos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Fenótipo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/metabolismo , Remodelação Vascular
2.
Dig Dis Sci ; 69(6): 2215-2222, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38594433

RESUMO

BACKGROUND: When unintentional pancreatic duct access occurs during difficult biliary cannulation, the double guidewire (DGW) or transpancreatic sphincterotomy (TPS) may be utilized. DGW can be easily switched to TPS due to the existing guidewire in the pancreatic duct. However, the efficacy of TPS after DGW, named sequential DGW-TPS technique, versus primary TPS has not been assessed. AIMS: Our aim was to compare the benefits and adverse events of sequential DGW-TPS technique and primary TPS. METHODS: We performed a comparative retrospective cohort study that enrolled a total of 117 patients with native papillae. The patients were divided into one of 2 groups according to the primary bile duct access technique (sequential DGW-TPS or primary TPS), both with pancreatic stenting. RESULTS: Between November 2017 and May 2023, a total of 84 patients were grouped into sequential DGW-TPS and 33 into primary TPS. The overall post-ERCP pancreatitis (PEP) rate was 4.3% in the entire cohort, with no statistical differences were observed between the groups in terms of PEP rates (P = 0.927), PEP severity (P = 1.000), first biliary cannulation success (P = 0.621), overall cannulation success (P = 1.000), hyperamylasemia incidence (P = 0.241), elevated amylase levels (P = 0.881), and postoperative hospital stay (P = 0.185). Furthermore, these results remained consistent in multivariable regression analysis. CONCLUSIONS: The sequential DGW-TPS technique showed a comparable safety and biliary cannulation success rate to primary TPS in difficult biliary cannulation. Given the potential long-term complications associated with TPS, DGW should be first if inadvertent pancreatic access occurs, with TPS serving as second only if DGW fails.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Ductos Pancreáticos , Pancreatite , Esfinterotomia Endoscópica , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Esfinterotomia Endoscópica/métodos , Esfinterotomia Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Pancreatite/etiologia , Pancreatite/epidemiologia , Ductos Pancreáticos/cirurgia , Cateterismo/métodos , Cateterismo/efeitos adversos , Cateterismo/instrumentação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Stents , Adulto
3.
Gastrointest Endosc ; 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38065509

RESUMO

BACKGROUND AND AIMS: Double-balloon endoscopy (DBE) is widely used in diagnosing small-bowel Crohn's disease (CD). However, CD misdiagnosis frequently occurs if inexperienced endoscopists cannot accurately detect the lesions. The CD evaluation may also be inaccurate owing to the subjectivity of endoscopists. This study aimed to use artificial intelligence (AI) to accurately detect and objectively assess small-bowel CD for more refined disease management. METHODS: We collected 28,155 small-bowel DBE images from 628 patients from January 2018 to December 2022. Four expert gastroenterologists labeled the images, and at least 2 endoscopists made the final decision with agreement. A state-of-the-art deep learning model, EfficientNet-b5, was trained to detect CD lesions and evaluate CD ulcers. The detection included lesions of ulcer, noninflammatory stenosis, and inflammatory stenosis. Ulcer grading included ulcerated surface, ulcer size, and ulcer depth. A comparison of AI model performance with endoscopists was performed. RESULTS: The EfficientNet-b5 achieved high accuracies of 96.3% (95% confidence interval [CI], 95.7%-96.7%), 95.7% (95% CI, 95.1%-96.2%), and 96.7% (95% CI, 96.2%-97.2%) for the detection of ulcers, noninflammatory stenosis, and inflammatory stenosis, respectively. In ulcer grading, the EfficientNet-b5 exhibited average accuracies of 87.3% (95% CI, 84.6%-89.6%) for grading the ulcerated surface, 87.8% (95% CI, 85.0%-90.2%) for grading the size of ulcers, and 85.2% (95% CI, 83.2%-87.0%) for ulcer depth assessment. CONCLUSIONS: The EfficientNet-b5 achieved high accuracy in detecting CD lesions and grading CD ulcers. The AI model can provide expert-level accuracy and objective evaluation of small-bowel CD to optimize the clinical treatment plans.

4.
BMC Gastroenterol ; 23(1): 247, 2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37475007

RESUMO

PURPOSE: To assess the efficacy of double-balloon endoscopy (DBE) for the detection of small-bowel strictures in Crohn's disease (CD). METHODS: This tertiary-referral hospital cohort study was conducted between January 2018 and May 2022. CD patients with symptoms of small-bowel stricture were enrolled sequentially. All of the patients were subjected to both computed tomography enterography (CTE) and DBE, and their symptoms of stricture were assessed using the Crohn's Disease Obstructive Score (CDOS). The diagnostic yield of DBE was compared to that of CTE, and the relationship between the DBE findings and CDOS was investigated. The factors influencing the DBE diagnosis were examined using Cox regression analysis. RESULTS: This study included 165 CD patients. The CDOS scores were higher in 95 patients and lower in 70 patients. DBE detected 92.7% (153/165) and CTE detected 85.5% (141/165) of the strictures. The DBE diagnostic yields were 94.7% (90/95) in the high CDOS patients and 91.4% (64/70) in the low CDOS patients (P = 0.13). Patients with a history of abdominal surgery and abscess had a lower diagnosis rate in the multivariate analysis. CONCLUSION: DBE has been demonstrated to be an efficient diagnostic method for detecting small bowel strictures in CD patients. Additionally, there was no difference in the diagnostic yields between patients with low and high obstructive scores.


Assuntos
Doença de Crohn , Obstrução Intestinal , Humanos , Doença de Crohn/complicações , Doença de Crohn/diagnóstico por imagem , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/etiologia , Intestino Delgado/diagnóstico por imagem , Estudos de Coortes , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/etiologia , Endoscopia Gastrointestinal/métodos , Enteroscopia de Duplo Balão
5.
J Biochem Mol Toxicol ; 37(9): e23422, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37350538

RESUMO

Melatonin possesses potent hepatoprotective properties, but it remains to be elucidated whether melatonin has a therapeutic effect on monocrotaline (MCT)-induced hepatic sinusoidal obstruction syndrome (HSOS). In this study, male Sprague Dawley rats were intraperitoneally injected with melatonin or the same volume of vehicle at 0 and 24 h after MCT intragastric administration. Next, hematoxylin-eosin staining and electron microscopy were performed to evaluate the hepatic sinusoidal injury of rats. Endothelial cell marker RECA-1 was observed by immunohistochemistry. Hepatic oxidative stress was analyzed by detecting malondialdehyde, glutathione S-transferase, and reactive oxygen species. Assessment of liver function was carried out by analysis of serum aspartate aminotransferase, alanine aminotransferase, total bilirubin, and albumin levels. Real-time polymerase chain reaction and Western blot analysis were used to identify liver Sirtuin-3 (SIRT3) and active matrix metallopeptidase 9 (MMP-9) expression. Besides, liver sinusoidal endothelial cells (LSECs) were used for the in vitro functional verification experiment. Specifically, liver histology of the melatonin-treated groups showed that the pathological damages caused by MCT were significantly attenuated, total HSOS scores were decreased, and the elevation of serum hyaluronic acid observed in the model group was also reduced. Moreover, melatonin treatment also improved the survival of rats after partial hepatectomy. Administration of melatonin ameliorated MCT-induced LSECs injury, hepatic oxidative stress, and hepatic dysfunction. Furthermore, melatonin treatment increased SIRT3 expression while attenuating MMP-9 activity in liver tissues. Cell experiment also demonstrated that SIRT3 might mediate the protective effect of melatonin on LSECs. Collectively, our study provided the potential rationale for the application of melatonin for the prevention of MCT-induced HSOS.


Assuntos
Hepatopatia Veno-Oclusiva , Melatonina , Sirtuína 3 , Ratos , Masculino , Animais , Hepatopatia Veno-Oclusiva/induzido quimicamente , Hepatopatia Veno-Oclusiva/tratamento farmacológico , Hepatopatia Veno-Oclusiva/patologia , Melatonina/farmacologia , Melatonina/uso terapêutico , Monocrotalina/toxicidade , Sirtuína 3/metabolismo , Ratos Sprague-Dawley , Células Endoteliais/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Fígado/metabolismo
6.
Surg Endosc ; 37(4): 2873-2884, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36509948

RESUMO

BACKGROUND AND OBJECTIVES: Submucosal tunnel endoscopic resection (STER) is an effective technique for treating esophageal submucosal tumors, but the efficacy and safety of treating esophageal submucosal tumors with internal traction method-assisted STER have not been determined. The objectives of this study were to assess the feasibility, safety, and efficacy of internal traction method-assisted STER for the removal of esophageal submucosal tumors. PATIENTS AND METHODS: Eighty patients who underwent STER for esophageal submucosal tumors were included in the study. They were randomized and assigned to the two groups. The dual-knife method was used for STER. Forty patients underwent conventional STER (control group) and 40 underwent internal traction method-assisted STER in which self-made rubber band traction with clips was used (study group). In the study group, one end of the self-made rubber band was fixed on the surface of esophageal submucosal tumors with a clip, and the other end of the self-made rubber band was set on the anal side of the contralateral esophageal wall with a clip. RESULTS: STER was successful in all cases. Lesion features and demographics were similar between the two groups. In addition, broad exposure of the submucosal tissue was obtained by applying tension to the self-made rubber band traction with clips. The en bloc resection rate and complete resection rate were both 100% in the study group. However, the en bloc resection rate and complete resection rate were 85.0% and 100%, respectively, in the control group. Complications, such as perforation and pneumomediastinum, were significantly reduced in the study group, and there was a significant difference in the number of occurrences of bleeding, operation duration, fasting time, and patient length of stay between the study group and control group (P < 0.05). During the mean 13.7 month follow-up, there were no patients with esophageal fistula, recurrence, or distant metastasis in either group. CONCLUSIONS: This original study showed that esophageal submucosal tumors could be effectively and safely treated with internal traction method-assisted STER, and this technique might be superior to conventional STER due to its fewer complications, shorter operation duration, and shorter inpatient length of stay.


Assuntos
Ressecção Endoscópica de Mucosa , Fístula Esofágica , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Ressecção Endoscópica de Mucosa/efeitos adversos , Método Simples-Cego , Tração , Neoplasias Esofágicas/cirurgia , Resultado do Tratamento , Estudos Retrospectivos
7.
Dig Dis Sci ; 68(11): 4252-4258, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37672151

RESUMO

BACKGROUND: Common bile duct microlithiasis (CBDM) with a diameter of ≤ 3 mm can pass spontaneously without causing any symptoms, but in some cases, it can also cause severe cholangitis and pancreatitis. The optimal strategy for managing CBDM is yet to be determined. METHODS: Data of 154 patients with CBDM were collected and divided into two groups: with endoscopic retrograde cholangiopancreatography (with ERCP, n = 82) and without ERCP (n = 72). Clinical outcomes, including the incidence of unfavorable outcomes (UOs), such as cholangitis and pancreatitis, were observed and compared between the two groups. RESULTS: The incidence of UOs was significantly lower in the ERCP group than in the without ERCP group (3.7% vs. 23.6%, respectively, p < 0.001). Moreover, the total number of readmissions was also lower in the ERCP group than in the without ERCP group (p < 0.001). A multivariate analysis adjusted for age, sex, and the American Society of Anesthesiologists (ASA) class revealed that endoscopic sphincterotomy (EST) and cholecystectomy were associated with a lower risk of UOs. CONCLUSION: The high rate of UOs in CBDM patients without ERCP suggests that its natural clinical course may not be as favorable as previously suggested. This finding implies that efforts should be made to clear the bile ducts.

8.
BMC Gastroenterol ; 22(1): 457, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36380275

RESUMO

BACKGROUND: Crohn's disease (CD), an inflammatory bowel disease (IBD), is a complex and heterogeneous disease characterized by nonspecific transmural inflammation of the gastrointestinal tract. CD has a variety of potential causes with no effective treatment available yet. Current clinical laboratory findings from patients do not provide direct indication of the status of mucosal inflammation in the intestine. Recently, it has been found that intestinal inflammation is generally associated with increased levels of 5-hydroxytryptamine (5-HT), which acts as an important gastrointestinal signaling molecule in intestinal homeostasis by stimulating specific receptors. Most previous researches were carried out in vitro or with animal models, and there was a lack of authentic clinical research. In this study, clinical specimens from patients with Crohn's disease were used to investigate the expression of 5-hydroxytryptamine 7 receptor (5-HT7R) in the induction and development of chronic non-specific inflammatory bowel disease. METHODS: Patients with CD admitted to the Department of Gastroenterology in the First Affiliated Hospital of Anhui Medical University between June 2014 and January 2018 were recruited, among which 28 were in active disease and 32 were in remission. In addition, 20 patients who had no obvious abnormality by colonoscopy in the hospital during the same time period were recruited into the control group. Data of clinical disease activity (CDAI), CD endoscopic score (SES-CD) and magnetic resonance score (MaRIA) were collected from those two groups of patients. The expression and distribution of 5-HT7R were investigated and their correlations with clinical CDAI, MaRIA, and endoscopic SES-CD scores were analyzed. RESULTS: Our study demonstrated that 5-HT7R is expressed in intestinal neurons and CD11C-positive cells in human colon. In CD11c/CD86 double-positive cells in the bowel, 5-HT7R expression was significantly increased in the inflammatory area in the bowel of CD patients, and it was closely related to disease severity, MaRIA, and SES-CD scores. CONCLUSION: The expression of 5-HT7R was significantly correlated with the degree of gut inflammation in CD patients and could be a potential biomarker for disease activity and the therapeutic efficacy in patients with Crohn's Disease.


Assuntos
Doença de Crohn , Doenças Inflamatórias Intestinais , Animais , Humanos , Doença de Crohn/patologia , Serotonina , Mucosa Intestinal/patologia , Colonoscopia , Doenças Inflamatórias Intestinais/patologia , Índice de Gravidade de Doença , Inflamação/patologia
9.
Int J Colorectal Dis ; 37(9): 1953-1961, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35927341

RESUMO

PURPOSE: Fecal calprotectin (FC) levels can reflect the level of intestinal inflammation. Crohn's disease (CD), which affects the small bowel, has not been linked to FC levels. We determined if FC levels and endoscopic activity were related by performing double-balloon endoscopy (DBE). METHODS: Herein, patients with small bowel CD diagnosed by DBE between January 2020 and January 2022 were prospectively observed. Feces and blood samples of patients were collected before performing DBE and checked for the levels of FC and serological biomarkers. The endoscopic activity and mucosal healing (MH) were evaluated using the partial simple endoscopic score (pSES-CD). RESULTS: In all 254 CD patients, FC levels were correlated with pSES-CD (r = 0.775, P < 0.001). Even in patients with isolated small bowel CD, FC levels were strongly correlated with pSES-CD (r = 0.753, P < 0.001). In all patients, FC as an endoscopic remission indicator was found to have an area under the curve (AUC) of 0.872, with a cut-off value of 156.09 µg/g. In patients with isolated small bowel CD, FC yielded a high AUC of 0.865 for predicting endoscopic remission, with a cut-off value of 211.48 µg/g, sensitivity of 73.95%, and specificity of 91.30%. FC was optimally cut-off at 76.99 µg/g to predict MH in accordance with the AUC of 0.877. CONCLUSIONS: Using DBE findings, FC was found to be significantly correlated with pSES-CD. Even in isolated small bowel CD, FC may be a more reliable marker of accurately predicting endoscopic remission and MH.


Assuntos
Doença de Crohn , Complexo Antígeno L1 Leucocitário , Biomarcadores , Colonoscopia , Doença de Crohn/diagnóstico , Endoscopia Gastrointestinal , Fezes/química , Humanos , Índice de Gravidade de Doença
10.
J Cell Biochem ; 122(9): 926-933, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31692102

RESUMO

Amplified in breast cancer 1 (AIB1) is overexpression in various cancers and promotes tumor cell proliferation, survival, and invasiveness. However, the role of AIB1 in the regulation of gastric cancer (GC) cell epithelial-mesenchymal transition (EMT) is still largely unclear. In the present study, immunohistochemistry showed that AIB1 was upregulated in our cohort of patients with GC and correlated with poor survival. Knockdown of AIB1 reduced the invasive ability of GC cells, downregulated the expression of epithelial cell marker E-cadherin, and upregulated mesenchymal cell marker vimentin. AIB1 overexpression elicited the opposite effect. PI-103, the inhibitor of the PI3K/AKT signaling, partially reversed AIB1 overexpression mediated a decrease in E-cadherin and an increase in vimentin. The present data demonstrated that AIB1 augmented the EMT via activation of PI3K/AKT signaling. In conclusion, our results suggested a novel role of AIB1 in GC invasion and EMT and raised the possibility of using this molecule as an indicator for GC treatment.

11.
Scand J Gastroenterol ; 56(12): 1427-1433, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34487462

RESUMO

BACKGROUND AND AIMS: Accurate serological assays are desirable for the diagnosis of inflammatory bowel disease (IBD). We identify an antigen-like substance called Crohn's disease (CD) antibody binding polypeptide (CABP). As a serological marker, anti-CABP may contribute to the diagnosis of IBD. The present study aims to evaluate the clinical role of anti-CABP as a serological antibody for IBD. METHODS: Using enzyme-linked immunosorbent assay (ELISA), serum anti-CABP, anti-Saccharomyces cerevisiae antibody (ASCA) and perinuclear anti-neutrophil cytoplasmic antibody (pANCA), titers were tested in 168 CD patients, 123 ulcerative colitis (UC) patients and 170 controls. The correlation between serum antibody and clinical characteristics was investigated. The diagnostic potential of the anti-CABP was evaluated by receiver operating characteristic (ROC) analysis. RESULTS: The titers of anti-CABP (IgA or IgG) and ASCA IgG of CD patients were significantly higher than non-CD group (all p < .01). In the differential diagnosis of CD and non-CD, anti-CABP IgA revealed an area under the curve (AUC) of 0.706 and anti-CABP IgG demonstrated an AUC of 0.788. As an individual antibody, anti-CABP could effectively distinguish CD from non-CD (AUC 0.816), and the diagnostic efficacy was better than that of ASCA (AUC 0.680). The combined use of anti-CABP, ASCA and pANCA significantly improved the diagnostic value (AUC 0.857). Anti-CABP positive rates were associated with perianal lesions and disease location in CD patients (both p < .05). CONCLUSIONS: Our results suggested that anti-CABP could be used as a serological marker to assist the diagnosis of CD. CLINICAL TRIAL REGISTRATION: This trial is registered with clinical trial registration unique identifier ChiCTR2000037094.


Assuntos
Colite Ulcerativa , Doença de Crohn , Anticorpos Anticitoplasma de Neutrófilos , Anticorpos Antifúngicos , Biomarcadores , Humanos , Saccharomyces cerevisiae
13.
Dig Dis Sci ; 63(12): 3359-3366, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29974378

RESUMO

BACKGROUND: Acute pancreatitis (AP) is a common acute gastrointestinal disorders. Increasing evidence indicated that autophagy is involved in the development of AP. Resolvin D1 is an endogenous pro-resolving lipid mediator, which can protect mice from cerulein-induced acute pancreatitis and facilitate autophagy in macrophage, but its mechanism remians unclear. AIMS: To investigate the effect of resolvin D1 on autophagy in mouse models of cerulein-induced AP. METHODS: C57BL/6 mice were randomly divided into control group, AP group and resolvin D1 group. The models of cerulein-induced AP were constructed by intraperitoneally cerulein. Resolvin D1 group was established by intraperitoneally resolvin D1 based on AP models, simultaneously, control group received normal saline. The severity of AP, the level of inflammatory cytokines, the number of autophagic vacuoles, and the expression of autophagy-related markers were evaluated among three groups. RESULTS: The AP models were established successfully. Compared to control group, the number of autophagic vacuoles and expressions of autophagy-related markers including Beclin-1, p62 and LC3-II were increased in AP models, In contrast, the degree of inflammation and levels of inflammatory cytokines in AP models were reduced after resolvin D1 treatment. Moreover, resolvin D1 attenuated the number of autophagic vacuoles and expressions of autophagy-related markers. CONCLUSIONS: Autophagic flux is impaired in cerulein-induced AP. Resolvin D1 ameliorate the severity of mice with cerulein-induced acute pancreatitis, possible attributing to its reducing impaired autophagy and restoring autophagic flux.


Assuntos
Autofagia , Ácidos Docosa-Hexaenoicos/farmacologia , Pancreatite Necrosante Aguda , Animais , Anti-Inflamatórios/farmacologia , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Proteína Beclina-1/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Infusões Parenterais/métodos , Ativação de Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/metabolismo , Pancreatite Necrosante Aguda/tratamento farmacológico , Pancreatite Necrosante Aguda/metabolismo , Resultado do Tratamento
14.
Scand J Gastroenterol ; 51(9): 1093-9, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27152547

RESUMO

OBJECTIVE: It remains controversial whether 6-thioguanine nucleotide (6-TGN)-based dose adjusting can be beneficial in azathioprine (AZA) therapy. This study is designed to assess the role of 6-TGN concentrations in maintaining clinical remission in Chinese patients with Crohn's disease (CD). MATERIAL AND METHOD: We performed a prospective observational study and collected data of CD patients in the First Affiliated Hospital of Anhui Medical University from June 2013 to April 2014. Demographic material, CD activity index, 6-TGN concentration, and laboratory tests were recorded at baseline and at each visit. In addition, 6-TGN was measured when drug adverse effects occurred. All patients achieved maintenance stage were administered a stable AZA dose at least 3 months before enrollment and were followed up at least 12 months. Thiopurine S-methyltransferase (TPMT) genotype was measured before AZA treatment. RESULTS: Sixty-nine patients receiving maintenance therapy were analyzed. A positive correlation was found between 6-TGN levels and AZA dose (r = 0.258, p = 0.032). The mean 6-TGN concentration was 302.06 ± 115.84 in the remission group vs. 264.94 ± 164.53 pmol/8 × 10(8) RBC in those with active disease (t = 0.847, p = 0.40), and 197.74 ± 66.54 pmol/8 × 10(8) RBC in patients who relapsed vs. 310.26 ± 122.38 pmol/8 × 10(8) RBC for those in sustained remission (t= -2.541, p = 0.013). In the leukopenia group, the 6-TGN concentration was 469.11 ± 115.53 pmol/8 × 10(8) RBC vs. 257.31 ± 83.74 pmol/8 × 10(8) RBC in the non-leukopenia group (t = 7.622, p < 0.001). There was a significant negative correlation between leukocyte count and 6-TGN concentration (r= -0.326, p = 0.006). CONCLUSIONS: 6-TGN measurement is a helpful method of preventing disease relapse and avoiding leukopenia in individual azathioprine maintenance therapy.


Assuntos
Azatioprina/administração & dosagem , Doença de Crohn/tratamento farmacológico , Nucleotídeos de Guanina/sangue , Imunossupressores/administração & dosagem , Tionucleotídeos/sangue , Adulto , Azatioprina/efeitos adversos , Doença de Crohn/genética , Monitoramento de Medicamentos/métodos , Eritrócitos/química , Feminino , Humanos , Imunossupressores/efeitos adversos , Contagem de Leucócitos , Leucopenia/induzido quimicamente , Leucopenia/prevenção & controle , Masculino , Metiltransferases/genética , Estudos Prospectivos , Adulto Jovem
16.
Dig Dis Sci ; 60(2): 375-81, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25293822

RESUMO

BACKGROUND AND AIM: Previous studies have revealed significantly increased levels of plasma and mucosal homocysteine (Hcy) in patients with Crohn's disease (CD); however, whether Hcy is involved in intestinal fibrosis of CD remains unclear. This study aimed to investigate the effects of Hcy on intestinal fibrosis in TNBS/ethanol-induced colitis and to elucidate its potential mechanisms. METHODS: Sprague-Dawley rats were divided into 4 groups: normal control, normal + Hcy injection, TNBS model and TNBS model + Hcy injection. Hyperhomocysteinemia was induced by subcutaneous injection of Hcy. DAI, CMDI and HI were calculated to evaluate the severity of colitis. Masson trichrome staining was performed to assess the severity of fibrosis. The plasma and mucosal levels of Hcy were measured by HPLC-FD. The levels of IL-1ß, IL-6, TNF-α, TGF-ß1, CTGF, MMP-2,9 and collagen I, III in the colon were determined by ELISA, and the mRNA expressions of TGF-ß1, MMP-2,9 and TIMP-1 were detected by RT-PCR. RESULTS: Hcy was found to increase the scores of DAI, CMDI and HI; levels of IL-1ß, Il-6, TNF-α, TGF-ß1, CTGF, MMP-2,9 and collagen I, III; and mRNA expressions of TGF-ß1, MMP-2,9 and TIMP-1 in colonic tissue of rats with TNBS/ethanol-induced colitis. CONCLUSIONS: Hcy promotes intestinal fibrosis in rats with TNBS/ethanol-induced colitis, the underlying mechanisms of which may be attributed to its effects of increasing inflammatory damage, promoting the expression of profibrogenic cytokines and influencing MMPs/TIMPs balance.


Assuntos
Colite/induzido quimicamente , Colo/patologia , Homocisteína , Hiper-Homocisteinemia/induzido quimicamente , Ácido Trinitrobenzenossulfônico , Animais , Colite/sangue , Colite/patologia , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Colo/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Etanol , Fibrose , Homocisteína/sangue , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/patologia , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Ratos Sprague-Dawley
17.
Scand J Gastroenterol ; 49(4): 424-33, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24533622

RESUMO

BACKGROUND: Patients with severe ulcerative colitis (SUC) have a high risk of requiring colectomy or resorting to a second-line treatment. However, neither clinical outcomes nor factors predictive of poor response have been clearly established in the treatment of SUC. OBJECTIVE: To assess prospectively the effects and predictors of corticosteroids (CS) use in clinical outcomes of SUC during 1 year of follow-up. MATERIAL AND METHODS: Consecutive inpatients with SUC, who had been treated with intravenous CS, were enrolled. Patients were monitored by clinical, laboratory, and endoscopic examinations, and the data were recorded for 1 year. Univariate and multivariate analyses were performed at 1 week. RESULTS: There were 22.6% (14/62) nonresponders at 7 days. Several predictors were associated with nonresponse to CS. These included Mayo Score at baseline (p = 0.007), partial Mayo Score, number of bowel movements, blood presence in stool, abdominal pain, and levels of C-reactive protein (CRP), hemoglobin (Hgb), platelet count (PLT), and erythrocyte sedimentation rate (ESR) on day 3 (p < 0.05). Multiple logistic regression analysis identified the Partial Mayo Score at day 3 as an independent predictor of outcome (p = 0.012). A total of 12 patients underwent colectomy within 1 year. The short-term response rates to intravenous cyclosporin (CsA) and infliximab (IFX) in SUC were 71.4% (5/7) and 77.8% (7/9), respectively. CONCLUSIONS: Many patients with SUC eventually became refractory to or dependent on CS. The Mayo score and laboratory characteristics were factors useful in predicting short-term outcome of CS treatment. Secondary medical therapy can help avoid emergency surgery.


Assuntos
Corticosteroides/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Adolescente , Corticosteroides/administração & dosagem , Adulto , Idoso , Feminino , Fármacos Gastrointestinais/administração & dosagem , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento
18.
Dig Dis Sci ; 59(12): 2992-6, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25030943

RESUMO

OBJECTIVES: Acute pancreatitis is one of the most common complications of endoscopic retrograde cholangiopancreatography (ERCP). Numerous studies have shown that administered nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the incidence of acute pancreatitis after ERCP. Little is known, however, about the mechanism of NSAIDs in preventing pancreatitis (PEP). METHODS: In this study, we assigned patients to receive a single dose of intramuscular diclofenac 75 mg immediately after ERCP (diclofenac group) or without (control group). The primary outcome measure was the occurrence of PEP. The serum amylase levels were measured before ERCP and at 3 and 24 h post-procedure in all patients. The Lipoxin A4 (LXA4), Resolvin D1 (Rvd1), and Resolvin E1 (RvE1) levels were measured before ERCP, and 3 and 24 h after the procedure in 30 patients from the diclofenac group and 30 patients from the control group. RESULTS: A total of 120 patients were enrolled and completed the follow-up. The overall incidence of PEP was 13.3% (16/120). It occurred in four of 60 patients (6.67%) in the diclofenac group and in 12 of 60 patients (20.00%) in the control group (p = 0.032). The LxA4, RvD1, and RvE1 levels in the diclofenac group at 3 h after ERCP were significantly increased compared with before ERCP (p < 0.05). Compared with the control group, the LxA4, RvD1, and RvE1 levels in the diclofenac group at 3 and 24 h after ERCP were significantly increased (p < 0.05). CONCLUSIONS: Intramuscular diclofenac after ERCP can reduce the incidence of PEP. This may be related to the fact that diclofenac can increase the levels of LxA4, RvD1, and RvE1.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Diclofenaco/uso terapêutico , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/análogos & derivados , Lipoxinas/metabolismo , Pancreatite/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Ácido Eicosapentaenoico/metabolismo , Humanos , Lipoxinas/genética , Pancreatite/etiologia
19.
Therap Adv Gastroenterol ; 17: 17562848231224842, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38250016

RESUMO

Background: It is unclear how clinical and endoscopic factors affect the attainment of endoscopic remission (ER) in patients with small bowel Crohn's disease (SB-CD) who are infliximab-naïve. Objectives: We aimed to identify the effect of different factors on attaining ER using double-balloon endoscopy (DBE) evaluation. Design: A single-center retrospective observational study was conducted from 1 January 2018 to 30 November 2022. Among 262 patients who were screened for isolated SB-CD by baseline DBE, 108 patients were assessed for effectiveness during maintenance infliximab therapy by a second DBE evaluation. Methods: DBE findings before and after infliximab therapy were compared. ER was defined as a simple endoscopic score for CD (SES-CD) below 3, and segmental ER as SES-CD activity of 0. Multivariate regression with calculations of odds ratios (OR) was used to determine the impact of different factors on attaining ER. Results: In all, 41 patients (38.0%) achieved ER. An elevated C-reactive protein at week 6 was independently associated with a decreased probability of ER [OR: 0.86, 95% confidence interval (CI) = 0.75-0.98, p = 0.03]. Segmental ER of the terminal ileum, rather than the proximal ileum, was associated with a higher rate of ER (60.9% versus 38.2%, p = 0.01). High baseline SES-CD (⩾16) was unrelated to overall ER. For patients with disease in the terminal ileum, those with moderate/severe disease were less likely to attain segmental ER than those with mild disease [adjusted odds ratios (aOR): 0.27, 95% CI: 0.09-0.83, p = 0.02]. A large ulcer in the terminal ileum was associated with a lower rate of segmental ER (aOR: 0.18, 95% CI: 0.06-0.56, p = 0.01). Conclusion: For infliximab-naïve patients with SB-CD, the overall severity of the endoscopic score was unrelated to attainment of ER. Patients were less likely to attain segmental ER if they had greater endoscopic inflammation or larger ulcers in the terminal ileum.

20.
World J Clin Cases ; 12(7): 1284-1289, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38524517

RESUMO

BACKGROUND: Gastrinoma is characterized by an excessive release of gastrin, leading to hypersecretion of gastric acid, subsequently resulting in recurrent peptic ulcers, chronic diarrhea, and even esophageal strictures. This case report aims to improve awareness and facilitate early diagnosis and treatment of gastrinoma by presenting a rare case of gastrinoma with refractory benign esophageal stricture (RBES). Additionally, it highlights the persistent challenges that gastroenterologists encounter in managing RBES. CASE SUMMARY: This case demonstrates a patient with gastrinoma who developed RBES and complete esophageal obstruction despite management with maximal acid suppressive therapy, multiple endoscopic bougie dilations and endoscopic incisional therapy (EIT). CONCLUSION: It is essential to diagnose gastrinoma as early as possible, as inadequately controlled acid secretion over an extended period increases the risk of developing severe esophageal strictures. In patients with esophageal strictures causing complete luminal obstruction, blind reopening EIT presents challenges and carries a high risk of perforation.

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