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1.
Dig Dis Sci ; 68(7): 3032-3042, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36943591

RESUMO

BACKGROUND AND AIMS: The activation of pancreatic stellate cells (PSCs) plays a key role in the occurrence and development of chronic pancreatitis (CP) and pancreatic fibrosis, which is related to the process of epithelial-mesenchymal transition (EMT). This study was designed to investigate the effect and mechanism of Tcf21 (one of tumor suppressor genes) on pancreatic inflammation and fibrosis in vivo and in vitro. METHODS: C57BL/6 male mice were intraperitoneally injected with caerulein for 6 weeks to establish CP animal model. Fixed pancreatic tissue paraffin-embedded sections were used for immunohistochemistry staining of Tcf21, fibrosis-related markers (α-SMA), interstitial markers (Vimentin) and epithelial markers (E-cadherin). Western blotting and qRT-PCR assay were performed to analyze the change of expression of the above markers after stimulation of TGF-ß1 or overexpressed Tcf21 lentivirus transfection in human pancreatic stellate cells (HPSCs). RESULTS: The pancreatic expression of α-SMA and Vimentin of CP mice significantly increased, while the expression of Tcf21 and E-cadherin significantly decreased. TGF-ß1 could promote activation and EMT process of HPSCs, and inhibited the expression of Tcf21. Overexpression of Tcf21 could significantly down-regulate the expression of α-SMA, Fibronectin and Vimentin, and up-regulated the expression of ZO-1 of HPSCs. Cell Counting Kit-8 assay and scratch wound-healing assay results showed that overexpression of Tcf21 could significantly inhibit the cell migration and proliferation of HPSCs. CONCLUSIONS: Overexpression of Tcf21 could significantly alleviate the activation, proliferation, migration of PSCs by regulating the EMT process. Tcf21 had a potential prospect of a new target for CP therapy.


Assuntos
Pancreatite Crônica , Fator de Crescimento Transformador beta1 , Humanos , Masculino , Camundongos , Animais , Fator de Crescimento Transformador beta1/metabolismo , Transição Epitelial-Mesenquimal/genética , Vimentina/genética , Células Estreladas do Pâncreas/patologia , Camundongos Endogâmicos C57BL , Fibrose , Pancreatite Crônica/patologia , Caderinas/genética , Caderinas/metabolismo
2.
BMC Gastroenterol ; 22(1): 216, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35505286

RESUMO

BACKGROUND AND AIMS: Cholecystectomy is performed for most gallbladder polyps (GPs). However, cholecystectomy results concerning complications in some patients. For benign GPs, adoption of gallbladder-preserving surgery is worth to recommend. We describe our experiences performing gallbladder-preserving polypectomy for GPs by embryonic-natural orifice transumbilical endoscopic surgery (E-NOTES) with a gastric endoscopy. METHODS: This is a retrospective study of patients with GPs who underwent gallbladder-preserving polypectomy by E-NOTES with a gastric endoscopy from April 2018 to September 2019 in our hospital. The operative time, intraoperative hemorrhage, intraoperative and postoperative complications, gallbladder emptying function were obtained and analyzed. RESULTS: The procedure was performed successfully in all 12 patients with 5 cases of single polyp and 7 cases of multiple polyps. The range of GPs size was 2 mm to 15 mm. The mean operation time was (95.33 ± 23.08) minutes (55-135 min). There were no adverse events including heavy bleeding, mortality and conversion to open surgery during operation. All patients were discharged in 4-5 days after surgery without postoperative complications such as delayed bleeding, fever, peritonitis, intra-abdominal abscess and abdominal wall incisional hernia. All patients were followed up at 1, 3, 6, and 12 months postoperation who had almost no visible incision on the umbilical region, no recurrent GPs. The gallbladder emptying function decreased one month after surgery, and gradually improved 3, 6 and 12 months after surgery. CONCLUSION: E-NOTES gallbladder-preserving polypectomy is a safe and effective option for patients with GPs and is close to scar-free surgery which can be performed in routine clinical practice.


Assuntos
Colecistectomia Laparoscópica , Doenças da Vesícula Biliar , Pólipos , Colecistectomia Laparoscópica/métodos , Endoscopia Gastrointestinal , Doenças da Vesícula Biliar/cirurgia , Humanos , Pólipos/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Umbigo/cirurgia
3.
Dig Dis Sci ; 67(1): 208-215, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33559090

RESUMO

AIMS: Quinolone-containing triple therapy has been considered as the second-line therapy for eradication of Helicobacter pylori (H. pylori). At present, there are no data to show the efficacy and safety of antofloxacin-based rescue therapy for the eradication of H. pylori, and this pilot clinical trial was designed. METHODS: A total of 196 patients who failed H. pylori eradication using the clarithromycin-based or metronidazole-based triple or bismuth quadruple therapy were randomly allocated to one of the following rescue eradication therapy groups: AEA group (antofloxacin 200 mg once daily, esomeprazole 20 mg + amoxicillin 1000 mg twice daily) for 14 days, or LEA group (levofloxacin 500 mg once daily, esomeprazole 20 mg + amoxicillin 1000 mg twice daily) for 14 days. The minimal inhibitory concentrations were tested by the E-test method. The gyrA mutation was analyzed by sequencing. Follow-up 13/14C-urea breath test was examined at 1 month after discontinuation. RESULTS: A total of 178 eligible patients were included in this study. The eradication rate was significantly higher in AEA group than in LEA group according to both ITT (87.6% vs. 68.5%; P = 0.002) and PP analyses (90.7% vs. 70.1%; P = 0.001). ITT analyses indicated that the eradication rate was significantly higher in AEA group than in LEA group with Asn87 mutation (78.9% vs. 31.3%; P = 0.005) and levofloxacin-resistant strains (76.9% vs. 44.2%; P = 0.003). Two groups exhibited similar adverse event rates (AEA 14.6% vs. LEA 20.2%, P = 0.323). CONCLUSIONS: The findings showed that antofloxacin may be a promising candidate in rescue therapy for H. pylori eradication failure in China.


Assuntos
Amoxicilina/administração & dosagem , Esomeprazol/administração & dosagem , Gastrite , Infecções por Helicobacter , Levofloxacino/administração & dosagem , Ofloxacino/análogos & derivados , Adulto , Antibacterianos/administração & dosagem , Testes Respiratórios/métodos , China , Quimioterapia Combinada , Feminino , Gastrite/tratamento farmacológico , Gastrite/microbiologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Testes de Sensibilidade Microbiana/métodos , Ofloxacino/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Resultado do Tratamento
4.
J Cell Mol Med ; 24(17): 9667-9681, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32678498

RESUMO

Chronic pancreatitis (CP) is characterized by persistent inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement with fibrotic tissue. Currently, the clinical therapeutic scheme of CP is mainly symptomatic treatment including pancreatic enzyme replacement, glycaemic control and nutritional support therapy, lacking of specific therapeutic drugs for prevention and suppression of inflammation and fibrosis aggravating in CP. Here, we investigated the effect of isoliquiritigenin (ILG), a chalcone-type dietary compound derived from licorice, on pancreatic fibrosis and inflammation in a model of caerulein-induced murine CP, and the results indicated that ILG notably alleviated pancreatic fibrosis and infiltration of macrophages. Further in vitro studies in human pancreatic stellate cells (hPSCs) showed that ILG exerted significant inhibition on the proliferation and activation of hPSCs, which may be due to negative regulation of the ERK1/2 and JNK1/2 activities. Moreover, ILG significantly restrained the M1 polarization of macrophages (RAW 264.7) via attenuation of the NF-κB signalling pathway, whereas the M2 polarization was hardly affected. These findings indicated that ILG might be a potential anti-inflammatory and anti-fibrotic therapeutic agent for CP.


Assuntos
Ceruletídeo/efeitos adversos , Chalconas/farmacologia , Macrófagos/efeitos dos fármacos , Células Estreladas do Pâncreas/efeitos dos fármacos , Pancreatite Crônica/induzido quimicamente , Pancreatite Crônica/tratamento farmacológico , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Fibrose/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Células Estreladas do Pâncreas/metabolismo , Pancreatite Crônica/metabolismo , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos
5.
J Gastroenterol Hepatol ; 35(2): 343-352, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31318997

RESUMO

BACKGROUND AND AIM: Diabetes mellitus (DM) is a common complication of idiopathic chronic pancreatitis (ICP), which impairs the quality of life for patients. This study aimed to identify risk factors and develop nomogram for DM in ICP to help early diagnosis. METHODS: Idiopathic chronic pancreatitis patients admitted to our center from January 2000 to December 2013 were included. Cumulative rates of DM were calculated by Kaplan-Meier method. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on training cohort, risk factors for DM were identified through Cox proportional hazards regression model, and nomogram was developed. Internal and external validations were performed based on the training and validation cohort, respectively. RESULTS: Totally, 1633 patients with ICP were finally enrolled. The median follow-up duration was 9.8 years. DM was found in 26.3% (430/1633) of patients after the onset of CP. Adult at onset of ICP, biliary stricture at/before diagnosis of CP, steatorrhea at/before diagnosis of CP, and complex pathologic changes in main pancreatic duct were identified risk factors for DM development. The nomogram achieved good concordance indexes in the training and validation cohorts, respectively, with well-fitted calibration curves. CONCLUSIONS: Risk factors were identified, and nomogram was developed to determine the risk of DM in ICP patients. Patients with one or more of the risk factors including adult at onset of ICP, biliary stricture at/before diagnosis of CP, steatorrhea at/before diagnosis of CP, and complex pathologic changes in main pancreatic duct have higher incidence of DM.


Assuntos
Diabetes Mellitus/etiologia , Nomogramas , Pancreatite Crônica/complicações , Idade de Início , Ductos Biliares/patologia , Constrição Patológica , Humanos , Ductos Pancreáticos/patologia , Fatores de Risco , Esteatorreia
6.
Digestion ; 101(4): 473-483, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31238312

RESUMO

BACKGROUND: Pancreatic stones are pathognomonic of chronic pancreatitis (CP). This study aimed to determine the incidence, identify risk factors, and develop a nomogram for pancreatic stones in CP patients. METHODS: Patients with CP admitted to our center from January 2000 to December 2013 were enrolled. Cumulative rates of pancreatic stones after the onset of CP and after the diagnosis of CP were calculated. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on the training cohort, risk factors were identified through Cox proportional hazards regression model, and nomogram was developed. Internal and external validations were performed based on the training and validation cohort, respectively. RESULTS: With a total of 2,153 CP patients, pancreatic stones were detected in 1,626 (75.5%) patients, with a median follow-up of 7.8 years. Age at the onset of CP, body mass index, smoking, diabetes mellitus, pancreatic pseudocyst, biliary stricture, severe acute pancreatitis, and type of pain were identified risk factors for pancreatic stones development. The nomogram with these 8 factors achieved good accuracy. CONCLUSIONS: The nomogram achieved an individualized prediction of pancreatic stones development in CP. It may help the management of pancreatic stones.


Assuntos
Cálculos/etiologia , Nomogramas , Pancreatopatias/etiologia , Pancreatite Crônica/complicações , Fatores de Tempo , Adulto , Cálculos/epidemiologia , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pancreatopatias/epidemiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco
7.
Pharmacol Res ; 147: 104357, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31356863

RESUMO

Chronic pancreatitis (CP) is characterized by persistent inflammation and fibrosis of the pancreas. To date, no clinical therapy is available to reverse the inflammatory damage or pancreatic fibrosis associated with CP. This study systematically investigated the effect of Dasatinib, a multiple tyrosine kinases (TKs) inhibitor, on pancreatic fibrosis and inflammation in vivo and in vitro. We found that Dasatinib notably ameliorated pancreatic fibrosis and infiltration of macrophages in a model of caerulein-induced murine CP. Further RNA-seq and phosphoproteomic analysis and in vitro validation assays indicated that Dasatinib exerted a marked inhibition on the proliferation and activation of PSCs, which may be resulted from increased GSK3ß-mediated ß-catenin cytosol retention by inhibiting upstream multiple TKs (such as PDGFR and Src) and MAPK cascades (including ERK1/2 and p38 MAPK). In addition, Dasatinib significantly restrained both the M1 and M2 polarization of macrophages, and impeded its recruitment and crosstalk with PSCs. Our findings indicated that Dasatinib is a potential anti-inflammatory and anti-fibrotic therapeutic strategy for CP.


Assuntos
Anti-Inflamatórios/uso terapêutico , Dasatinibe/uso terapêutico , Pancreatite Crônica/tratamento farmacológico , Animais , Movimento Celular/efeitos dos fármacos , Ceruletídeo , Fibrose , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Células Estreladas do Pâncreas/efeitos dos fármacos , Células Estreladas do Pâncreas/metabolismo , Pancreatite Crônica/induzido quimicamente , Pancreatite Crônica/patologia , Células RAW 264.7 , Cicatrização/efeitos dos fármacos
8.
J Clin Gastroenterol ; 53(3): e91-e100, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-28961573

RESUMO

GOALS: To identify the risk factors and develop nomograms for common bile duct (CBD) stricture in chronic pancreatitis (CP) patients. BACKGROUND: CBD stricture is a common complication in CP and has a variable clinical presentation ranging from asymptomatic to overt jaundice and cholangitis. STUDY: Patients with CP admitted to Changhai Hospital (Shanghai, China) from January 2000 to December 2013 were enrolled. Cumulative rates of CBD stricture after onset and diagnosis of CP were calculated. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. On the basis of the training cohort, risk factors for CBD stricture and symptomatic CBD stricture were identified through Cox proportional hazards regression model, and nomograms was developed, respectively. Internal and external validations were performed based on the training and validation cohort, respectively. RESULTS: With a total of 2153 patients, the median duration of follow-up was 7.0 years. CBD strictures were detected in 340 (15.8%) patients, whereas 159 of them were symptomatic. Male gender, age at onset of CP, smoking, body mass index, and morphology of main pancreatic duct were identified risk factors for CBD stricture development. Age at onset of CP, body mass index, and type of pain were identified risk factors for symptomatic CBD stricture development. Both nomograms achieved good concordance indexes with well-fitted calibration curves. CONCLUSIONS: The nomogram achieved an individualized prediction of symptomatic CBD stricture development in CP patients. It may help the early diagnosis and intervention of symptomatic CBD stricture and reduce the rates of severe adverse events.


Assuntos
Doenças do Ducto Colédoco/epidemiologia , Nomogramas , Pancreatite Crônica/complicações , Adulto , Fatores Etários , China , Estudos de Coortes , Doenças do Ducto Colédoco/etiologia , Doenças do Ducto Colédoco/patologia , Constrição Patológica/etiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Adulto Jovem
9.
BMC Gastroenterol ; 19(1): 31, 2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30764766

RESUMO

BACKGROUND: Autoimmune factor was regarded as one of the risk factors in the pathogenesis of chronic pancreatitis (CP), especially for autoimmune pancreatitis (AIP). However, whether autoimmune factor plays a role in non-AIP CP or not was unknown. METHODS: Hospitalized patients with non-AIP CP from January 2010 to October 2016 were detected for 22 autoantibodies at the time of hospital admission. Autoantibodies with frequency > 0.5% were enrolled to calculate the frequency in historial healthy controls through literature search in PubMed. Differentially expressed autoantibodies were determined between patients and historial healthy controls, and related factors were identified by multivariate logistic regression analysis. RESULTS: In a total of 557 patients, 113 cases were detected with 19 kinds of positive autoantibodies, among them anti-ß2-glycoprotein I (ß2-GPI) antibody was most frequent (9.16%). Compared with historial healthy controls, the frequencies of serum ß2-GPI and anti SS-B antibody in patients were significantly higher, while frequencies of anti-smooth muscle antibody and anticardiolipin antibody were significantly lower (all P < 0.05). Multivariate logistic regression analysis result showed that diabetes mellitus (OR = 2.515) and common bile duct stricture (OR = 2.844) were the risk factors of positive ß2-GPI antibody in patients while diabetes mellitus in first-/second-/third-degree relatives (OR = 0.266) was the protective factor. There were no related factors for other three differentially expressed autoantibodies. CONCLUSIONS: Four autoantibodies were expressed differentially between patients with non-AIP CP and historial healthy controls. Due to limited significance for diagnosis and treatment of chronic pancreatitis, autoantibodies detection is not recommended conventionally unless suspected of AIP.


Assuntos
Autoanticorpos/sangue , Pancreatite Crônica/diagnóstico , Pancreatite Crônica/imunologia , Adulto , Anticorpos Anticardiolipina/sangue , Anticorpos Antinucleares/sangue , Estudos Transversais , Humanos , Pessoa de Meia-Idade , Músculo Liso/imunologia , Estudos Prospectivos , beta 2-Glicoproteína I/imunologia
10.
J Gastroenterol Hepatol ; 34(2): 466-473, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30552715

RESUMO

BACKGROUND AND AIM: Pancreatic extracorporeal shock wave lithotripsy (P-ESWL) is a first-line treatment for chronic pancreatitis (CP) patients with pancreatic stones. However, the performance of P-EWSL in geriatric patients remains unclear. We aimed to evaluate the safety and efficacy of P-ESWL for them. METHODS: This prospective study was conducted in painful CP patients who underwent P-ESWL. Patients aged over 65 years were included in geriatric group; patients aged under 65 years were assigned to control group. For the long-term follow-up investigation, geriatric patients were matched with patients from the control group in a 1:1 ratio. Primary outcomes were complications of P-ESWL and pain relief. Secondary outcomes included stone clearance, physical and mental health, quality of life score, changes in exocrine and endocrine pancreatic function, and survival. RESULTS: From March 2011 to March 2016, P-ESWL was performed in 1404 patients (72 in the geriatric group and 1332 in the control group). No significant differences were observed in complications of P-ESWL between the two groups (P = 0.364). Among the 67 (67/72, 93.1%) geriatric patients who underwent follow up for 4.02 years, complete pain relief was achieved in 53 patients, which was not significantly different from that of matched controls (54/70; P = 0.920). The death in the geriatrics was significantly higher (P = 0.007), but none of them were correlated with P-ESWL. CONCLUSIONS: P-ESWL is safe and effective for geriatric CP patients with pancreatic stones. It can promote significant pain relief and stone clearance and improve quality of life and mental and physical health.


Assuntos
Cálculos/terapia , Litotripsia , Pancreatite Crônica/terapia , Adulto , Fatores Etários , Idoso , Cálculos/diagnóstico , Feminino , Avaliação Geriátrica , Humanos , Litotripsia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pancreatite Crônica/diagnóstico , Estudos Prospectivos , Qualidade de Vida , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
11.
BMC Gastroenterol ; 18(1): 182, 2018 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-30518343

RESUMO

BACKGROUND: Pediatric patients always suffer from chronic pancreatitis (CP), especially those with steatorrhea. This study aimed to identify the incidence of and risk factors for steatorrhea in pediatric CP. To our best knowledge, there is no pediatric study to document the natural history of steatorrhea in CP. METHODS: CP patients admitted to our center from January 2000 to December 2013 were enrolled. Patients were assigned to the pediatric (< 18 years old) and adult group according to their age at onset of CP. Cumulative rates of steatorrhea in both groups were calculated. Risk factors for both groups were identified, respectively. RESULTS: The median follow-up duration for the whole cohort was 7.6 years. In a total of 2153 patients, 13.5% of them were pediatrics. The mean age at the onset and the diagnosis of CP in pediatrics were 11.622 and 19.727, respectively. Steatorrhea was detected in 46 patients (46/291, 15.8%) in the pediatric group and in 447 patients (447/1862, 24.0%) in the adult group. Age at the onset of CP (hazard ratio [HR], 1.121), diabetes mellitus (DM, HR, 51.140), and severe acute pancreatitis (SAP, HR, 13.946) was identified risk factor for steatorrhea in the pediatric group. CONCLUSIONS: Age at the onset of CP, DM and SAP were identified risk factors for the development of steatorrhea in pediatric CP patients. The high-risk populations were suggested to be followed up closely. They may benefit from a full adequate pancreatic exocrine replacement therapy.


Assuntos
Pancreatite Crônica/complicações , Esteatorreia/etiologia , Adolescente , Adulto , Idade de Início , Criança , Complicações do Diabetes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite Crônica/terapia , Fatores de Risco , Índice de Gravidade de Doença
12.
Endoscopy ; 49(5): 447-455, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28403504

RESUMO

Background and aims Pancreatic extracorporeal shock wave lithotripsy (P-ESWL) is recommended as the first-line treatment for pancreatic stones. However, how well P-ESWL performs in pediatric patients remains unclear. We aimed to evaluate the safety and efficacy of P-ESWL for pediatric patients with chronic pancreatitis. Methods This prospective observational study was conducted in patients with painful chronic pancreatitis who underwent P-ESWL. Patients aged under 18 years were included in the pediatric group; patients aged over 18 years who underwent P-ESWL in the same period were assigned to the control group. For investigation of long-term follow-up, the pediatric group were matched with patients from the control group in a 1:1 ratio. The primary outcomes were P-ESWL complications and pain relief. The secondary outcomes included: stone clearance, physical and mental health, quality of life score, and growth and developmental state. Results From March 2011 to March 2015, P-ESWL was performed in 1135 patients (72 in the pediatric group, 1063 in the control group). No significant differences were observed in the occurrence of P-ESWL complications between the two groups (11.1 % vs. 12.8 %; P = 0.68). Among the 67 pediatric patients (93.1 %) who underwent follow-up for 3.0 years (range 1.3 - 5.2), complete pain relief was achieved in 52 patients (52 /67; 77.6 %); this value was not significantly different from that of the matched controls (55 /69; 79.7 %; P = 0.94). Conclusions P-ESWL is safe and effective for pediatric patients with chronic pancreatitis. It can promote significant pain relief and stone clearance, and can benefit growth and development.


Assuntos
Dor Abdominal/terapia , Litíase/terapia , Litotripsia/efeitos adversos , Pancreatite Crônica/terapia , Dor Abdominal/etiologia , Adolescente , Adulto , Criança , Pré-Escolar , Colangiopancreatografia Retrógrada Endoscópica , Feminino , Seguimentos , Nível de Saúde , Humanos , Litíase/complicações , Masculino , Saúde Mental , Pessoa de Meia-Idade , Medição da Dor , Pancreatite Crônica/etiologia , Estudos Prospectivos , Qualidade de Vida , Adulto Jovem
13.
J Gastroenterol Hepatol ; 32(7): 1403-1411, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28127800

RESUMO

BACKGROUND AND AIM: Pancreatic pseudocyst is a common complication of chronic pancreatitis. The identification of risk factors and development of a nomogram for pancreatic pseudocysts in chronic pancreatitis patients may contribute to the early diagnosis and intervention of pancreatic pseudocysts. METHODS: Patients with chronic pancreatitis admitted to our center from January 2000 to December 2013 were enrolled. Cumulative rates of pancreatic pseudocysts after the onset of chronic pancreatitis and after the diagnosis of chronic pancreatitis were calculated. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on the training cohort, risk factors were identified through Cox proportional hazards regression model, and nomogram was developed. Internal and external validations were performed based on the training and validation cohort, respectively. RESULTS: With a total of 1998 patients, pancreatic pseudocysts were detected in 228 (11.41%) patients. Age at the onset of chronic pancreatitis, smoking, and severe acute pancreatitis were identified risk factors for pancreatic pseudocysts development while steatorrhea and pancreatic stones were protective factors. Incorporating these five factors, the nomogram achieved good concordance indexes of 0.735 and 0.628 in the training and validation cohorts, respectively, with well-fitted calibration curves. CONCLUSION: The nomogram achieved an individualized prediction of pancreatic pseudocysts development in chronic pancreatitis. It may help the early diagnosis and management of pancreatic pseudocysts.


Assuntos
Nomogramas , Pseudocisto Pancreático/diagnóstico , Pseudocisto Pancreático/etiologia , Pancreatite Crônica/complicações , Adulto , Idade de Início , Estudos de Coortes , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pseudocisto Pancreático/epidemiologia , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Fatores de Risco , Adulto Jovem
15.
Int Immunopharmacol ; 130: 111691, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38367466

RESUMO

In the realm of fibroinflammatory conditions, chronic pancreatitis (CP) stands out as a particularly challenging ailment, lacking a dedicated, approved treatment. The potential of Pirfenidone (PFD), a drug originally used for treating idiopathic pulmonary fibrosis (IPF), in addressing CP's fibrotic aspects has sparked new interest. This investigation focused on the role of PFD in diminishing fibrosis and immune response in CP, using a mouse model induced by caerulein. The research extended to in vitro studies examining the influence of PFD on pancreatic stellate cells' (PSCs) behavior and the polarization of macrophages into M1 and M2 types. Advanced techniques like RNA sequencing and comprehensive data analyses were employed to decode the molecular interactions of PFD with PSCs. Supplementary experiments using techniques such as quantitative real-time PCR, western blotting, and immunofluorescence were also implemented. Results showed a notable reduction in pancreatic damage in PFD-treated mice, manifested through decreased acinar cell atrophy, lower collagen deposition, and a reduction in macrophage presence. Further investigation revealed PFD's capacity to hinder PSCs' migration, growth, and activation, alongside a reduction in the production and secretion of extracellular matrix proteins. This effect is primarily achieved by interfering with signaling pathways such as TGF-ß/Smad, Wnt/ß-catenin, and JAK/STAT. Additionally, PFD selectively hampers M1 macrophage polarization through the STAT3 pathway, without impacting M2 polarization. These outcomes highlight PFD's dual mechanism in moderating PSC activity and M1 macrophage polarization, positioning it as a promising candidate for CP therapy.


Assuntos
Células Estreladas do Pâncreas , Pancreatite Crônica , Piridonas , Humanos , Células Estreladas do Pâncreas/metabolismo , Células Estreladas do Pâncreas/patologia , Pancreatite Crônica/tratamento farmacológico , Pancreatite Crônica/induzido quimicamente , Pâncreas/patologia , Macrófagos/metabolismo , Fibrose
16.
Cell Signal ; 118: 111135, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38479555

RESUMO

BACKGROUND: Pancreatic fibrosis is one of the most important pathological features of chronic pancreatitis (CP) and pancreatic stellate cells (PSCs) are the key cells of fibrosis. As an extracellular matrix (ECM) glycoprotein, cartilage oligomeric matrix protein (COMP) is critical for collagen assembly and ECM stability and recent studies showed that COMP exert promoting fibrosis effect in the skin, lungs and liver. However, the role of COMP in activation of PSCs and pancreatic fibrosis remain unclear. We aimed to investigate the role and specific mechanisms of COMP in regulating the profibrotic phenotype of PSCs and pancreatic fibrosis. METHODS: ELISA method was used to determine serum COMP in patients with CP. Mice model of CP was established by repeated intraperitoneal injection of cerulein and pancreatic fibrosis was evaluated by Hematoxylin-Eosin staining (H&E) and Sirius red staining. Immunohistochemical staining was used to detect the expression changes of COMP and fibrosis marker such as α-SMA and Fibronectin in pancreatic tissue of mice. Cell Counting Kit-8, Wound Healing and Transwell assessed the proliferation and migration of human pancreatic stellate cells (HPSCs). Western blotting, qRT-PCR and immunofluorescence staining were performed to detect the expression of fibrosis marker, AKT and MAPK family proteins in HPSCs. RNA-seq omics analysis as well as small interfering RNA of COMP, recombinant human COMP (rCOMP), MEK inhibitors and PI3K inhibitors were used to study the effect and mechanism of COMP on activation of HPSCs. RESULTS: ELISA showed that the expression of COMP significantly increased in the serum of CP patients. H&E and Sirius red staining analysis showed that there was a large amount of collagen deposition in the mice in the CP model group and high expression of COMP, α-SMA, Fibronectin and Vimentin were observed in fibrotic tissues. TGF-ß1 stimulates the activation of HPSCs and increases the expression of COMP. Knockdown of COMP inhibited proliferation and migration of HPSCs. Further, RNA-seq omics analysis and validation experiments in vitro showed that rCOMP could significantly promote the proliferation and activation of HPSCs, which may be due to promoting the phosphorylation of ERK and AKT through membrane protein receptor CD36. rCOMP simultaneously increased the expression of α-SMA, Fibronectin and Collagen I in HPSCs. CONCLUSION: In conclusion, this study showed that COMP was up-regulated in CP fibrotic tissues and COMP induced the activation, proliferation and migration of PSCs through the CD36-ERK/AKT signaling pathway. COMP may be a potential therapeutic candidate for the treatment of CP. Interfering with the expression of COMP or the communication between COMP and CD36 on PSCs may be the next direction for therapeutic research.


Assuntos
Pancreatopatias , Pancreatite Crônica , Animais , Humanos , Camundongos , Proteína de Matriz Oligomérica de Cartilagem/metabolismo , Proteína de Matriz Oligomérica de Cartilagem/farmacologia , Proteína de Matriz Oligomérica de Cartilagem/uso terapêutico , Células Cultivadas , Colágeno Tipo I/metabolismo , Fibronectinas/metabolismo , Fibrose , Pancreatopatias/metabolismo , Células Estreladas do Pâncreas/metabolismo , Células Estreladas do Pâncreas/patologia , Pancreatite Crônica/tratamento farmacológico , Pancreatite Crônica/metabolismo , Pancreatite Crônica/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
17.
Therap Adv Gastroenterol ; 16: 17562848221147763, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36742013

RESUMO

Background: We previously reported that antofloxacin-based bismuth quadruple therapy was safe and effective for Helicobacter pylori (H. pylori) eradication. It is not clear whether the addition of Saccharomyces boulardii (S. boulardii) to antofloxacin-based quadruple therapy can improve the eradication rate of H. pylori and reduce adverse events. Objective: To investigate the effect of adding S. boulardii to antofloxacin-based quadruple therapy on the eradication rate of H. pylori and the adverse events. Design: Single-center, prospective randomized controlled study. Methods: A total of 172 patients with H. pylori infection were randomly assigned to the test and control groups. Patients in the control group (n = 86) received antofloxacin-based bismuth quadruple therapy for 14 days. On this basis, cases in the test group (n = 86) received S. boulardii 500 mg b.i.d. The eradication rate of H. pylori and adverse events were observed 4 weeks after the treatment. Results: There were no statistically significant differences in the eradication rates of H. pylori and frequency of diarrhea between the test group and control group (p > 0.05). The duration of diarrhea in the test group was significantly shorter than in the control group (p < 0.001). In addition, the two groups exhibited similar adverse event rates for epigastric pain, abdominal distention, dizzy, vomiting, and rash (p > 0.05). The severity of adverse reactions was similar between the two groups (p > 0.05), and most of them had mild adverse events. Conclusion: Although the addition of S. boulardii to antofloxacin-based quadruple therapy could not improve the eradication rate of H. pylori, it could shorten the time of antibiotic-associated diarrhea and reduce the incidence of diarrhea. Trial registration number: ChiCTR2200056931.

18.
Medicine (Baltimore) ; 101(51): e32408, 2022 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-36595813

RESUMO

RATIONALE: Familial adenomatous polyposis (FAP) is an autosomal dominant genetic disease, with a very high cancer rate. At present, endoscopic resection of polyps ≥ 1 cm is often chosen for patients with non-cancerous polyps who are unwilling to undergo surgery, and regular review is conducted. Once the polyps are pathologically confirmed to be cancerous, surgical resection of the diseased large intestine is generally recommended, but surgery often leads to a series of complications. So what do you do with cancer patients who don't want surgery? PATIENT CONCERNS: A 19-year-old woman presented with intermittent hematochezia with abdominal pain. A colonoscopy revealed hundreds of intestinal polyps. DIAGNOSES: The patient had a family history of FAP, and there were hundreds of polyps in the intestine. The pathology was adenomatous, and some polyps became cancerous, which met the diagnostic criteria of FAP. INTERVENTIONS: Endoscopic examination was arranged for the patient, the resection of intestinal polyps ≥ 1 cm was given priority, and other polyps were removed as far as possible. After that, metformin 500 mg orally was given twice a day, and endoscopic follow-up was conducted every 6 months. During each endoscopic follow-up, intestinal polyps ≥ 1 cm were preferred to be removed, and other polyps were removed as far as possible. OUTCOMES: The patient's abdominal pain and blood in the stool disappeared after endoscopic treatment. Cancerous polyps were found at the second and third follow-up visits, but the patient always refused surgical treatment. After 4 years of follow-up, polyp load was significantly reduced, abdominal pain and bloody stool symptoms did not appear again, and imaging examination showed no tumor recurrence and metastasis. LESSONS: Endoscopic polyp resection is an important method to treat the clinical symptoms of FAP. Metformin combined with endoscopic therapy is a good alternative for patients with familial polyposis who do not want surgery. When the polyp is cancerous and the polyp is radically resected by the endoscope, if the patient refuses additional surgery, oral metformin combined with endoscopic follow-up can be considered.


Assuntos
Polipose Adenomatosa do Colo , Carcinoma , Feminino , Humanos , Adulto Jovem , Adulto , Recidiva Local de Neoplasia , Polipose Adenomatosa do Colo/complicações , Polipose Adenomatosa do Colo/cirurgia , Polipose Adenomatosa do Colo/genética , Pólipos Intestinais , Dor Abdominal
19.
Medicine (Baltimore) ; 101(52): e32339, 2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36595974

RESUMO

BACKGROUND: Colonoscopy is the main kind of way to detect and treat diseases about large intestine, but during the examination and preparation, these 2 processes are able to lead abdominal pain, abdominal distention and other discomfort feel, which will cause patients to refuse the examination and become anxious. Painless and sedative endoscopy may reduce discomfort of patients, but there is a risk of adverse effects. Many studies have shown that playing music during colonoscopy can reduce discomfort and increase acceptance of colonoscopy, but the conclusion remains controversial. The 3 approaches of random, single-blind, controlled method were used to investigate the interventions effects of piano light music on satisfaction, anxiety and pain in patients undergoing colonoscopy. METHODS: A total of 216 patients were randomly divided into piano music group (n = 112, piano music played during colonoscopy) and control group (n = 104, no music during colonoscopy) to compare patients satisfaction, anxiety score, pain score, vital signs, endoscopic difficulty score, and willingness to undergo colonoscopy again. RESULTS: There were no significant differences in vital signs, pre-colonoscopic state anxiety score, and trait anxiety score before and after colonoscopy, and willingness to undergo colonoscopy again between the 2 groups (P > .05). The difficulty of colonoscopy operation and the score of state anxiety after colonoscopy in the piano group were lower than those in the control group (P < .05), and the satisfaction of colonoscopy process, pain management and overall service satisfaction were better than those of the control group (P < .05), and they were more likely to listen to music in the next examination (P < .001). CONCLUSION: The light music played by piano can relieve patients' anxiety, improve the satisfaction of colonoscopy process, pain management and service satisfaction, reduce the difficulty of colonoscopy, which have no obvious adverse reactions. Therefore, it is worthy of promotion.


Assuntos
Colonoscopia , Satisfação do Paciente , Humanos , Método Simples-Cego , Colonoscopia/efeitos adversos , Colonoscopia/métodos , Ansiedade/etiologia , Ansiedade/prevenção & controle , Dor Abdominal/etiologia
20.
Clin Res Hepatol Gastroenterol ; 46(7): 101987, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35777730

RESUMO

BACKGROUND: There is huge shortage of ERCP practitioners (ERCPists) in China, and ERCP training is urgently needed. ChangHai Advanced eNdoscopy Courses for ERCP (CHANCE) is a 4-month program for ERCP training since 2004. This study evaluated the efficiency of this short-term training model, and reported on the ERCP careers of the trainees following completion of the CHANCE program. METHODS: This study was a retrospective investigation included all the CHANCE trainees from Jan 2004 to Dec 2014. Questionnaires were sent to all trainees. The career competence percentage, ERCP careers and predictive factors of career competence were investigated and analyzed. RESULTS: A total of 413 trainees participated in the CHANCE program over 11 years covered by the survey and 258 questionnaires were valid for the study. The mean (SD) age of the trainees was 35.36 (4.17), and the male to female ratio was 4.4:1. The average follow-up time was 7.77 (3.44) years. A total of 173 (67.1%) trainees had achieved career competence. In terms of ERCP careers, the mean annual ERCP volume was 120.60 (96.67), with a complication percentage of 8.2%. Hospital qualification, compliance with follow-up learning guidance, participating academic activity, and practitioner type were identified predictive factors of career competence. CONCLUSIONS: As a short-term training program, the CHANCE achieved an acceptable career competence percentage, providing endoscopists more chances to learn ERCP and giving them appropriate training guidance for career competence. This training mode is worth promoting in developing countries with shortage of ERCPists.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Competência Clínica , Endoscopia Gastrointestinal , Feminino , Humanos , Masculino , Estudos Retrospectivos , Inquéritos e Questionários
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