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Márgenes de Escisión , Tumores Neuroendocrinos , Neoplasias del Recto , Terapia Recuperativa , Humanos , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Tumores Neuroendocrinos/cirugía , Tumores Neuroendocrinos/patología , Terapia Recuperativa/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Resección Endoscópica de la Mucosa/métodosRESUMEN
Fragment growing is an important ligand design strategy in drug discovery. In this study, we present FragGrow, a web server that facilitates structure-based drug design by fragment growing. FragGrow offers two working modes: one for growing molecules through the direct replacement of hydrogen atoms or substructures and the other for growing via virtual synthesis. FragGrow works by searching for suitable fragments that meet a set of constraints from an indexed 3D fragment database and using them to create new compounds in 3D space. The users can set a range of constraints when searching for their desired fragment, including the fragment's ability to interact with specific protein sites; its size, topology, and physicochemical properties; and the presence of particular heteroatoms and functional groups within the fragment. We hope that FragGrow will serve as a useful tool for medicinal chemists in ligand design. The FragGrow server is freely available to researchers and can be accessed at https://fraggrow.xundrug.cn.
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Diseño de Fármacos , Internet , Programas Informáticos , Ligandos , Modelos Moleculares , Interfaz Usuario-ComputadorRESUMEN
BACKGROUND: Post-endoscopic submucosal dissection electrocoagulation syndrome (PEECS) is an uncommon complication after colorectal endoscopic submucosal dissection (ESD). This study aimed to explore the risk factors of PEECS for superficial colorectal lesions based on the latest and consistent diagnostic criteria and to establish a predictive nomogram model. METHODS: This retrospective analysis included patients with superficial colorectal lesions who underwent endoscopic submucosal dissection (ESD) between June 2008 and December 2021 in our center. The independent risk factors of PEECS for superficial colorectal lesions were identified using least absolute shrinkage and selection operator (LASSO) logistic regression analysis, as well as univariate analysis and multivariate logistic regression, and derived predictive nomogram model was constructed. RESULTS: Among the 555 patients with superficial colorectal lesions enrolled, PEECS occurred in 45 (8.1%) patients. Multivariate logistic regression revealed that female sex (OR 3.94, P < 0.001), age > 50 years (OR 4.28, P = 0.02), injury to muscle layer (OR 10.38, P < 0.001), non-lifting sign (OR 2.20, P = 0.04) and inadequate bowel preparation (OR 5.61, P < 0.001) were independent risk factors of PEECS for superficial colorectal lesions. A predictive nomogram model was constructed based on the above five predictors. For this model, the area under the receiver operating characteristic (ROC) curve was 0.855, the calibration curve exhibited good consistency between the prediction and the actual observation, and the C-index was confirmed as 0.843 by bootstrap method. CONCLUSION: Female sex, age > 50 years, injury to muscle layer, non-lifting sign and inadequate bowel preparation were independent risk factors of PEECS for superficial colorectal lesions. The proposed nomogram could accurately predict the risk of PEECS for superficial colorectal lesions.
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Neoplasias Colorrectales , Electrocoagulación , Resección Endoscópica de la Mucosa , Nomogramas , Complicaciones Posoperatorias , Humanos , Femenino , Masculino , Persona de Mediana Edad , Factores de Riesgo , Estudios Retrospectivos , Resección Endoscópica de la Mucosa/efectos adversos , Resección Endoscópica de la Mucosa/métodos , Síndrome , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/patología , Electrocoagulación/efectos adversos , Electrocoagulación/métodos , AncianoRESUMEN
BACKGROUND: Dieulafoy's lesion (DL) is a rare and important cause of acute nonvariceal upper gastrointestinal bleeding (ANVUGIB), however, there is a lack of clear guidelines focus on the endoscopic hemostasis treatment for DL. Sclerotherapy, as the ANVUGIB guideline recommended endoscopic hemostasis method, is widely used in clinical practice. The aim of this study is to investigate the efficacy of sclerotherapy as the initial treatment for Dieulafoy's lesion of the upper gastrointestinal tract (UDL). METHODS: Patients with UDL who underwent the ANVUGIB standard endoscopic hemostasis between April 2007 and January 2023 were enrolled. The endoscopic therapy method was left to the discretion of the endoscopist. RESULTS: In total, 219 patients were finally obtained, with 74 (33.8%) receiving sclerotherapy and 145 (66.2%) receiving other standard endoscopic therapy. The rebleeding within 30 days was significantly lower in the sclerotherapy group compared to the other standard group (5.8% vs. 16.8%, p = 0.047). There were no significant differences between the two groups in terms of successful hemostasis rate (93.2% vs. 94.5%, p = 0.713), median number of red blood cell transfusions (3.5 vs. 4.0 units, p = 0.257), median hospital stay (8.0 vs. 8.0 days, p = 0.103), transferred to ICU rate (8.1% vs. 6.2%, p = 0.598), the need for embolization or surgery rate (12.2% vs. 9.7%, p = 0.567) and 30-day mortality (0 vs. 2.1%, p = 0.553). In addition, we found no difference in efficacy between sclerotherapy alone and combination (3.1% vs. 8.1%, p = 0.714). Further analysis revealed that thermocoagulation for hemostasis was associated with a higher rate of rebleeding (28.6% vs. 3.1%, p = 0.042) and longer hospital stay (11.5 vs. 7.5 days, p = 0.005) compared to sclerotherapy alone. CONCLUSION: Sclerotherapy represents an effective endoscopic therapy for both alone and combined use in patients with upper gastrointestinal Dieulafoy's lesion. Therefore, sclerotherapy could be considered as initial treatment in patients with bleeding of UDL.
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Hemorragia Gastrointestinal , Hemostasis Endoscópica , Escleroterapia , Humanos , Escleroterapia/métodos , Masculino , Femenino , Hemorragia Gastrointestinal/terapia , Hemorragia Gastrointestinal/etiología , Persona de Mediana Edad , Anciano , Hemostasis Endoscópica/métodos , Resultado del Tratamiento , Estudios Retrospectivos , Adulto , RecurrenciaRESUMEN
BACKGROUND: Endoscopic submucosal dissection (ESD) was widely used for the removal of esophageal tumors, and post-endoscopic submucosal dissection electrocoagulation syndrome (PEECS) was one of the postoperative adverse events. The aim of this research was to develop and validate a model to predict electrocoagulation syndrome after endoscopic submucosal dissection of esophageal tumors. MATERIALS AND METHODS: Patients who underwent esophageal ESD in our hospital were retrospectively included. A predictive nomogram was established based on the results of multivariate logistic regression analysis, and bootstrapping resampling was used for internal validation. Besides, the clinical usefulness of the nomogram was evaluated using decision curve analysis (DCA) and clinical impact curve. RESULTS: A total of 552 patients who underwent esophageal ESD were included in the study, and the incidence of PPECS was 12.5% (69/552). Risk factors associated with PEECS (p < 0.1) were analyzed by multivariate logistic regression analysis, and the final model included four variables, namely gender, diabetes, tumor size and operation time. The predictive nomogram was constructed based on the above four variables, and the area under the ROC curve (AUC) was 0.811 (95% CI 0.767-0.855). The calibration curve of the nomogram presented good agreement between the predicted and actual probabilities. DCA showed that the model improved patient outcomes by helping to assess the risk of PEECS in patients compared to an all-or-no treatment strategy. In addition, the clinical impact curve of the model also indicates that the nomogram has a high clinical net benefit. CONCLUSION: In conclusion, we have developed a predictive nomogram for PEECS after ESD for esophageal tumors with good predictive accuracy and discrimination. This predictive nomogram can be effectively used to identify high-risk patients with PEECS, which will help clinicians in clinical decision-making and early intervention.
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Resección Endoscópica de la Mucosa , Neoplasias Esofágicas , Humanos , Nomogramas , Estudios Retrospectivos , Resección Endoscópica de la Mucosa/efectos adversos , Neoplasias Esofágicas/patología , Electrocoagulación/efectos adversosRESUMEN
Introduction: Fever is one of the postoperative complications of endoscopic submucosal dissection (ESD) and its derivative technology. However, there are few studies on risk factors for fever after ESD and its derivative technology. The aim of this study was to determine the incidence and related risk factors after ESD and its derivative technology for gastric lesions. Materials and methods: A retrospective review of patients with gastric lesions who were treated by ESD and its derivative technology in our hospital from January 2014 to January 2019 was conducted. Results: A total of 1955 patients were included in the present study. A total of 451 (23.1â%) patients presented with fever after ESD and its derived techniques. The highest fever temperature was 37.6 ± 3.12 °C, and the number of days with fever was 1.48 ± 0.85. Through single factor and multiple factor analysis, age (OR: 1.261, 95% CI: 1.009-1.576, p < 0.05), procedure time (OR: 1.457, 95% CI: 1.053-2.016, p < 0.05), postoperative gastric tube placement (OR: 2.098, 95% CI: 1:616-2.723, p < 0.05), intraoperative hemorrhage (OR: 1.537, 95% CI: 1.196-1.974, p < 0.05) and perforation (OR: 1.970, 95% CI: 1.531-2.535, p < 0.05) were independent risk factors for postoperative fever. Conclusion: Age ≥56 years old, procedure time ≥60 min, gastric tube placement, intraoperative hemorrhage and perforation were independent risk factors for postoperative fever after gastric ESD and its derivative technology. Attention should be given to such patients to minimize the risk of postoperative fever.
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The imminent discharge of Fukushima-contaminated water into the ocean would result in severe controversies and disputes concerning marine environment pollution in Japan and the neighboring countries. This paper argues that high similarities can be found between the disputes arising from the imminent discharge and those subject to compulsory conciliation under the dispute settlement mechanism of the law of the sea. Together with the advantages of compulsory conciliation in settling disputes related to the exercise of discretion by states, it is asserted that compulsory conciliation could become the best choice to settle the potential disputes arising from the imminent discharge between Japan and the neighboring countries. This article also draws attention to some essential issues related to the application of compulsory conciliation, including the establishment of jurisdiction and authorities of the conciliation commission, and the implementation of the conciliation report.
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Disentimientos y Disputas , Accidente Nuclear de Fukushima , Japón , Contaminación Ambiental , AguaRESUMEN
As a bulk solid waste with high alkalinity, red mud (RM) not only occupies a large amount of land and requires high maintenance costs, but also unavoidably generates serious hazards to the surrounding ecological environment. The comprehensive treatment of RM has become an enormous challenge for the green, low-carbon and high-quality development of the global alumina industry. To minimize the RM destruction to the ecology and the waste of secondary resources, the sustainable utilization of RM was widely investigated in the past decades, especially for the recovery of valuable metals. This paper systematically summarized the research status of recycling valuable metals (Al, Fe, Na, Ti, Sc, Ga, V and RE) from RM in recent years. The recycling technology mainly includes physical beneficiation, hydrometallurgy, pyrometallurgy and electrodialysis. The technical principles and characteristics as well as the current problems of various recovery processes from RM were comprehensively introduced, and the future development directions of sustainable utilization were also prospected. The advantages and disadvantages based on the different aspects of recovery efficiency, energy consumption and environmental impact were also discussed. The proposal of new technologies for the harmless, high-value and full utilization of RM is beneficial to the future research on the comprehensive utilization of bulk industrial solid wastes.
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Background: Nasogastric tube (NGT) placement is part of the post-operative management of upper gastrointestinal perforation, but its routine use in esophageal perforation (EP) caused by foreign bodies remains unclear. The purpose of this research was to investigate the necessity for routine NGT placement in patients with EP after endoscopic foreign body removal. Methods: A total of 323 patients diagnosed with EP caused by foreign bodies at the First Affiliated Hospital of Nanchang University between January 2012 and December 2021 were included in this retrospective study. Patients were divided into the NGT group and the non-NGT group according to whether or not NGT placement was performed. The perforation healing rate, post-operative adverse events, hospital stay, and death rate were analysed using a 1:1 propensity score matching model. Results: Before matching, there were 263 patients in the NGT group and 60 patients in the non-NGT group. There were significant differences in the time to treatment, infection, albumin, and types of endoscopy between the two groups, while the length of hospital stay in the NGT group was significantly longer than that in the non-NGT group. After 1:1 propensity score matching, 48 pairs of patients were matched between the two groups. The perforation healing rate, post-operative adverse events, length of hospital stay, and death rate did not show significant differences between the two groups. Conclusions: For patients with small EP caused by foreign bodies, routine NGT placement after endoscopic foreign body removal may be unnecessary.
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Fast and proper treatment of the tautomeric states for drug-like molecules is critical in computer-aided drug discovery since the major tautomer of a molecule determines its pharmacophore features and physical properties. We present MolTaut, a tool for the rapid generation of favorable states of drug-like molecules in water. MolTaut works by enumerating possible tautomeric states with tautomeric transformation rules, ranking tautomers with their relative internal energies and solvation energies calculated by AI-based models, and generating preferred ionization states according to predicted microscopic pKa. Our test shows that the ranking ability of the AI-based tautomer scoring approach is comparable to the DFT method (wB97X/6-31G*//M062X/6-31G*/SMD) from which the AI models try to learn. We find that the substitution effect on tautomeric equilibrium is well predicted by MolTaut, which is helpful in computer-aided ligand design. The source code of MolTaut is freely available to researchers and can be accessed at https://github.com/xundrug/moltaut. To facilitate the usage of MolTaut by medicinal chemists, we made a free web server, which is available at http://moltaut.xundrug.cn. MolTaut is a handy tool for investigating the tautomerization issue in drug discovery.
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Agua , IsomerismoRESUMEN
BACKGROUND: Endoscopic full-thickness resection is a common endoscopic procedure for treating gastrointestinal submucosal tumors. Nasogastric tube placement is frequently performed after abdominal surgery, but the routine use of this approach remains controversial. The aim of this research was to explore whether nasogastric tube placement after gastric endoscopic full-thickness resection is necessary. METHODS: A retrospective study enrolled patients who underwent gastric endoscopic full-thickness resection in our hospital between January 2014 and January 2019, and all the patients had a tumor size ≤ 2 cm. The patients were divided into two groups according to whether a nasogastric tube was placed. Postprocedural adverse events and hospital stay duration were compared between the two groups using 1:1 propensity score matching. RESULTS: A total of 461 patients were enrolled in this study, including 385 patients in the nasogastric tube group (NGT group) and 76 patients in the non-nasogastric tube group (non-NGT group). After matching, the baseline characteristics of 73 patients in the NGT group and 73 patients in the non-NGT group were balanced (p > 0.05). The postprocedural fever rate in the NGT group was significantly higher than that in the non-NGT group (23.3% vs. 9.6%, p = 0.044). 6.9% (5/73) of patients experienced severe nasogastric tube-related throat discomfort. However, the duration of hospitalization stay was not different between the two groups. CONCLUSIONS: For patients with tumor size ≤ 2 cm, routine nasogastric tube placement after gastric endoscopic full-thickness resection may be unnecessary.
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Intubación Gastrointestinal , Neoplasias , Humanos , Puntaje de Propensión , Estudios Retrospectivos , Intubación Gastrointestinal/efectos adversos , HospitalizaciónRESUMEN
INTRODUCTION: Post-endoscopic submucosal dissection electrocoagulation syndrome (PEECS) is a rare complication following endoscopic submucosal dissection (ESD). However, many aspects of PEECS are still controversial and there is a lack of up-to-date review. The aim of this article is to provide a comprehensive review on PEECS. AREAS COVERED: The English-language literature was searched for articles on PEECS, with a focus on its pathogenesis, definition, and diagnosis, incidence rate, risk factors, prevention, management, and prognosis. EXPERT OPINION: Many aspects of PEECS are still controversial such as etiology, diagnostic criteria, prevention and management. The recent studies tend to agree on the diagnostic criteria for PEECS, defined as localized abdominal tenderness and fever or inflammatory response without delayed perforation. Most patients with PEECS have a favorable prognosis with conservative treatment and more high-quality studies are needed in the controversial aspects mentioned above.
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Resección Endoscópica de la Mucosa , Humanos , Resección Endoscópica de la Mucosa/efectos adversos , Electrocoagulación/efectos adversos , Factores de Riesgo , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Molecular hybridization is a widely used ligand design method in drug discovery. In this study, we present MolHyb, a web server for structure-based ligand design by molecular hybridization. The input of MolHyb is a protein file and a seed compound file. MolHyb tries to generate novel ligands through hybridizing the seed compound with helper compounds that bind to the same protein target or similar proteins. To facilitate the job of getting helper compounds, we compiled a modeled protein-ligand structure database as an extension to crystal structures in the PDB database by placing the bioactive compounds in ChEMBL into their corresponding 3D protein binding pocket properly. MolHyb works by searching for helper compounds from the protein-ligand structure database and migrating chemical moieties from helper compounds to the seed compound efficiently. Hybridization is performed at both cyclic and acyclic bonds. The users can also input their own helper compounds to MolHyb. We hope that MolHyb will be a useful tool for rational drug design. MolHyb is freely available at http://molhyb.xundrug.cn/.
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Proteínas , Programas Informáticos , Sitios de Unión , Bases de Datos de Proteínas , Diseño de Fármacos , Internet , Ligandos , Proteínas/químicaRESUMEN
MicroRNAs (miRNAs/miRs) have aroused increasing attention in colorectal cancer (CRC) therapy. This study is designed for a detailed analysis of the roles of miR-16-5p and forkhead box K1 (FOXK1) in cell angiogenesis and proliferation during CRC in addition to their underlying mechanisms. CRC tissues and colon cancer cell lines (SW620 and HCT8) were investigated. qRT-PCR and Western blot were utilized to evaluate miR-16-5p and FOXK1 expression. Following gain- and loss-of-function assays on miR-16-5p or FOXK1, the effects of miR-16-5p and FOXK1 were assessed on cell angiogenesis and proliferation in CRC cells. A dual-luciferase reporter assay was employed to evaluate the binding relationship of miR-16-5p and FOXK1. Western blot was used to determine the effects of miR-16-5p and FOXK1 on key molecules of the PI3K/Akt/mTOR pathway. Highly expressed FOXK1 and lowly expressed miR-16-5p were observed in CRC cells and tissues. miR-16-5p overexpression or FOXK1 knockdown reduced CRC cell proliferation and angiogenesis of human umbilical vein endothelial cells co-cultured with the supernatant of CRC cells, whereas miR-16-5p silencing or FOXK1 upregulation caused opposite trends. Additionally, miR-16-5p negatively modulated FOXK1 expression. The blockade of the PI3K/Akt/mTOR pathway was triggered by miR-16-5p overexpression or FOXK1 silencing. In conclusion, miR-16-5p hampers cell angiogenesis and proliferation during CRC by targeting FOXK1 to block the PI3K/Akt/mTOR pathway.
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Neoplasias Colorrectales , MicroARNs , Línea Celular Tumoral , Proliferación Celular/genética , Neoplasias Colorrectales/genética , Células Endoteliales/metabolismo , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
BACKGROUND: Marginal ulcer bleeding is a cause of upper gastrointestinal bleeding, but the efficacy of emergency endoscopic hemostasis and risk factors for rebleeding have not been fully explored. The purpose of the current study was to investigate the rebleeding rate and risk factors after emergency endoscopic hemostasis for marginal ulcer bleeding. METHODS: We conducted a retrospective study of 105 patients who underwent emergency endoscopic hemostasis due to marginal ulcer bleeding from January 2015 to July 2021. Patients included in this study were divided into rebleeding and non-rebleeding groups. RESULTS: Among the 105 patients, 15.2% (16/105) patients developed rebleeding within 30 days after endoscopic hemostasis, and 87.5% of the patients had rebleeding within 7 days. The mean age of these patients was 60.3 ± 12.3 years, and 95 of them were male. In the univariate analysis, an ulcer size ≥10 mm, a PLT count <100 × 10^9/L and an AIMS65 score ≥2 were risk factors for rebleeding. According to the multivariable analysis, an ulcer size ≥10 mm (OR: 3.715; 95% CIs: 1.060-14.250; p = 0.043) and a PLT count <100 × 10^9/L (OR: 4.480; 95% CIs: 1.099-18.908; p = 0.035) were independent risk factors for rebleeding. CONCLUSION: Emergency endoscopic hemostasis is an effective treatment for marginal ulcer bleeding. An ulcer size ≥10 mm and a PLT count <100 × 10^9/L were independent risk factors for rebleeding within 30 days after endoscopic hemostasis for marginal ulcer bleeding.
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Hemostasis Endoscópica , Úlcera Péptica , Anciano , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Úlcera Péptica/complicaciones , Úlcera Péptica/terapia , Úlcera Péptica Hemorrágica/etiología , Úlcera Péptica Hemorrágica/cirugía , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Úlcera/complicaciones , Úlcera/terapiaRESUMEN
The protein-ligand scoring function plays an important role in computer-aided drug discovery and is heavily used in virtual screening and lead optimization. In this study, we developed a new empirical protein-ligand scoring function with amino acid-specific interaction components for hydrogen bond, van der Waals, and electrostatic interactions. In addition, hydrophobic, π-stacking, π-cation, and metal-ligand interactions are also included in the new scoring function. To better evaluate the performance of the AA-Score, we generated several new test sets for evaluation of scoring, ranking, and docking performances, respectively. Extensive tests show that AA-Score performs well on scoring, docking, and ranking as compared to other widely used traditional scoring functions. The performance improvement of AA-Score benefits from the decomposition of individual interaction into amino acid-specific types. To facilitate applications, we developed an easy-to-use tool to analyze protein-ligand interaction fingerprint and predict binding affinity using the AA-Score. The source code and associated running examples can be found at https://github.com/xundrug/AA-Score-Tool.
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Aminoácidos , Proteínas , Aminoácidos/metabolismo , Enlace de Hidrógeno , Ligandos , Simulación del Acoplamiento Molecular , Unión Proteica , Proteínas/químicaRESUMEN
Background: Fever is one of the postoperative adverse events of endoscopic submucosal dissection and its derived technique, but the probability and risk factors of postoperative fever are still unclear. The aim of the current study was to investigate the incidence and risk factors of postoperative fever after esophageal lesion removal. Methods: We conducted a retrospective study of 446 patients who underwent esophageal endoscopic submucosal dissection and its derived technique between January 2014 and January 2020. Cases included in this study were divided into fever and non-fever groups. Results: Postoperative fever developed in 135 patients (30.3%). The median (range) highest fever temperature was 38 (37.8-38.4)°C, the median (range) duration of fever was 1 (1-2) day, and 127 (94.1%) patients developed fever within 24 h after operation. Through logistic regression analysis, factors associated with postoperative fever were age (OR: 1.740, 95% CI: 1.005-3.013, p = 0.048), lesion size (OR: 2.007, 95% CI: 1.198-3.362, p = 0.008), operation time (OR: 3.007, 95% CI: 1.756-5.147, p < 0.001) and nasogastric tube placement (OR: 1.881, 95% CI: 1.165-3.037, p = 0.010), while prophylactic antibiotics (OR: 0.181, 95% CI: 0.082-0.401, p < 0.001) were negatively associated with fever. Conclusions: Age ≥52 years old, lesion size ≥19 mm, operation time ≥37 min, and nasogastric tube placement are risk factors for postoperative fever after esophageal endoscopic submucosal dissection and its derived technique, prophylactic antibiotic use after operation may help reduce fever rate. Attention should be paid to such patients to minimize the risk of postoperative fever.
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BACKGROUND: The over-the-scope clip (OTSC) is an innovative device and has been successfully used in endoscopic treatment, however, there is a lack of clinical data from China. The aim of this study is to investigate the OTSC applications in the treatment of upper non-variceal gastrointestinal bleeding (UNVGIB), perforations, and fistulas in China. METHODS: In total, 80 patients were treated with one OTSC respectively as first-line therapy in our endoscopy center between January 2016 and November 2020. Among them, 41 patients had UNVGIB, 34 patients had perforations, and five patients had fistulas. The technical and clinical success rates were used to assess the efficacy of OTSC on the above diseases. In addition, we compared the hemostatic efficacy of OTSC with the standard endoscopic therapy in ulcer bleeding and Dieulafoy's lesion by propensity score matching analysis. RESULTS: In general, the OTSCs were applied successfully in all patients and achieved 100% (80/80) technical success. The clinical success of all patients was 91.3% (73/80). Among 41 patients with UNVGIB, the clinical success was 85.4% (35/41); 6 patients presented with recurrence. For patients of Dieulafoy's lesion and under antithrombotic therapy, we found that OTSC treatment had both efficient and reliable hemostasis effects. In addition, according to the characteristics of ulcers, site of bleeding lesion, and Blatchford score, all patients received similar and reliable clinical success rates. After propensity score matching, we found that OTSC treatment had low rebleeding rates when compared with standard endoscopic therapy in both Dieulafoy's lesion (15.0 vs 30.0%) and ulcer bleeding (17.6 vs 29.4%). Among 34 patients with perforations, the clinical success was 100% (34/34). Among five patients with fistulas, only one patient failed in maintaining the OTSC before esophageal fistula healing, and the clip achieved an overall clinical success of 80% (4/5). CONCLUSION: The OTSC represents a safe and effective endoscopic therapy for UNVGIB, perforations, and fistulas as first-line treatment, especially for Dieulafoy's lesion or patients under antithrombotic therapy for UNVGIB, etc. However, OTSC application in these specific lesions or patients lacks adequate evidence as first-line treatment. Therefore, further larger sample and multi-center clinical trials are required to improve its indications in clinical treatment.
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BACKGROUND: Peptic ulcer bleeding remains a typical medical emergency with significant morbidity and mortality. Peptic ulcer rebleeding often occurs within three days after emergent endoscopic hemostasis. Our study aims to develop a nomogram to predict rebleeding within three days after emergent endoscopic hemostasis for high-risk peptic ulcer bleeding. METHODS: We retrospectively reviewed the data of 386 patients with bleeding ulcers and high-risk stigmata who underwent emergent endoscopic hemostasis between March 2014 and October 2018. The least absolute shrinkage and selection operator method was used to identify predictors. The model was displayed as a nomogram. Internal validation was carried out using bootstrapping. The model was evaluated using the calibration plot, decision-curve analyses, and clinical impact curve. RESULTS: Overall, 386 patients meeting the inclusion criteria were enrolled, with 48 patients developed rebleeding within three days after initial endoscopic hemostasis. Predictors contained in the nomogram included albumin, prothrombin time, shock, haematemesis/melena and Forrest classification. The model showed good discrimination and good calibration with a C-index of 0.854 (C-index: 0.830 via bootstrapping validation). Decision-curve analyses and clinical impact curve also demonstrated that it was clinically valuable. CONCLUSION: This study presents a nomogram that incorporates clinical, laboratory, and endoscopic features, effectively predicting rebleeding within three days after emergent endoscopic hemostasis and identifying high-risk rebleeding patients with peptic ulcer bleeding. Trial registration This clinical trial has been registered in the ClinicalTrials.gov (ID: NCT04895904) approved by the International Committee of Medical Journal Editors (ICMJE).
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Hemostasis Endoscópica , Úlcera Péptica , Humanos , Úlcera Péptica Hemorrágica/terapia , Recurrencia , Estudios RetrospectivosRESUMEN
Human oral bioavailability (HOB) is a key factor in determining the fate of new drugs in clinical trials. HOB is conventionally measured using expensive and time-consuming experimental tests. The use of computational models to evaluate HOB before the synthesis of new drugs will be beneficial to the drug development process. In this study, a total of 1588 drug molecules with HOB data were collected from the literature for the development of a classifying model that uses the consensus predictions of five random forest models. The consensus model shows excellent prediction accuracies on two independent test sets with two cutoffs of 20% and 50% for classification of molecules. The analysis of the importance of the input variables allowed the identification of the main molecular descriptors that affect the HOB class value. The model is available as a web server at www.icdrug.com/ICDrug/ADMET for quick assessment of oral bioavailability for small molecules. The results from this study provide an accurate and easy-to-use tool for screening of drug candidates based on HOB, which may be used to reduce the risk of failure in late stage of drug development.