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Background: High altitude de-acclimatization (HADA) is gradually becoming a public health concern as millions of individuals of different occupations migrate to high-altitude areas for work due to economic growth in plateau areas. HADA affects people who return to lower elevations after exposure to high altitudes. It causes significant physiological and functional changes that can negatively impact health and even endanger life. However, uncertainties persist about the detailed mechanisms underlying HADA. Methods: We established a population cohort of individuals with HADA and assessed variations in metabolite composition. Plasm samples of four groups, including subjects staying at plain (P) and high altitude (H) as well as subjects suffering from HADA syndrome with almost no reaction (r3) and mild-to-moderate reaction (R3) after returning to plain from high altitude, were collected and analyzed by Liquid Chromatography-Mass Spectrometry metabolomic. Multivariate statistical analyses were used to explore significant differences and potential clinical prospect of metabolites. Result: Although significantly different on current HADAS diagnostic symptom score, there were no differences in 17 usual clinical indices between r3 and R3. Further multivariate analyses showed isolated clustering distribution of the metabolites among the four groups, suggesting significant differences in their metabolic characteristics. Through K-means clustering analysis, we identified 235 metabolites that exhibited patterns of abundance change consistent with phenotype of HADA syndrome. Pathway enrichment analysis indicated a high influence of polyunsaturated fatty acids under high-altitude conditions. We compared the metabolites between R3 and r3 and found 107 metabolites with differential abundance involved in lipid metabolism and oxidation, suggesting their potential role in the regulation of oxidative stress homeostasis. Among them, four metabolites might play a key role in the occurrence of HADA, including 11-beta-hydroxyandrosterone-3-glucuronide, 5-methoxyindoleacetate, 9,10-epoxyoctadecenoic acid, and PysoPC (20:5). Conclusion: We observed the dynamic variation in the metabolic process of HADA. Levels of four metabolites, which might be provoking HADA mediated through lipid metabolism and oxidation, were expected to be explore prospective indices for HADA. Additionally, metabolomics was more efficient in identifying environmental risk factors than clinical examination when dramatic metabolic disturbances underlying the difference in symptoms were detected, providing new insights into the molecular mechanisms of HADAS.
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BACKGROUND: Acute pancreatitis (AP) has become a significant global health concern, and a high body mass index (BMI) has been identified as a key risk factor exacerbating this condition. Within this context, lipid metabolism assumes a critical role. The complex relationship between elevated BMI and AP, mediated by lipid metabolism, markedly increases the risk of complications and mortality. This study aimed to accurately define the correlation between BMI and AP, incorporating a comprehensive analysis of the interactions between individuals with high BMI and AP. METHODS: Mendelian randomization (MR) analysis was first applied to determine the causal relationship between BMI and the risk of AP. Subsequently, three microarray datasets were obtained from the GEO database. This was followed by an analysis of differentially expressed genes and the application of weighted gene coexpression network analysis (WGCNA) to identify key modular genes associated with AP and elevated BMI. Functional enrichment analysis was then performed to shed light on disease pathogenesis. To identify the most informative genes, machine learning algorithms, including Random Forest (RF), Support Vector Machine-Recursive Feature Elimination (SVM-RFE), and Least Absolute Shrinkage and Selection Operator (LASSO), were employed. Subsequent analysis focused on the colocalization of the Quantitative Trait Loci (eQTL) data associated with the selected genes and Genome-Wide Association Studies (GWAS) data related to the disease. Preliminary verification of gene expression trends was conducted using external GEO datasets. Ultimately, the diagnostic potential of these genes was further confirmed through the development of an AP model in mice with a high BMI. RESULTS: A total of 21 intersecting genes related to BMI>30, AP, and lipid metabolism were identified from the datasets. These genes were primarily enriched in pathways related to cytosolic DNA sensing, cytokineâcytokine receptor interactions, and various immune and inflammatory responses. Next, three machine learning techniques were utilized to identify HADH as the most prevalent diagnostic gene. Colocalization analysis revealed that HADH significantly influenced the risk factors associated with BMI and AP. Furthermore, the trend in HADH expression within the external validation dataset aligned with the trend in the experimental data, thus providing a preliminary validation of the experimental findings.The changes in its expression were further validated using external datasets and quantitative real-time polymerase chain reaction (qPCR). CONCLUSION: This study systematically identified HADH as a potential lipid metabolism-grounded biomarker for AP in patients with a BMI>30.
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Índice de Masa Corporal , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Pancreatitis , Sitios de Carácter Cuantitativo , Humanos , Pancreatitis/genética , Ratones , Animales , Biomarcadores/sangre , Biomarcadores/metabolismo , Perfilación de la Expresión Génica , Transcriptoma/genética , Aprendizaje Automático , Metabolismo de los Lípidos/genética , Redes Reguladoras de Genes , Factores de RiesgoRESUMEN
This study aimed to evaluate acute pancreatitis (AP) severity using convolutional neural network (CNN) models with enhanced computed tomography (CT) scans. Three-dimensional DenseNet CNN models were developed and trained using the enhanced CT scans labeled with two severity assessment methods: the computed tomography severity index (CTSI) and Atlanta classification. Each labeling method was used independently for model training and validation. Model performance was evaluated using confusion matrices, areas under the receiver operating characteristic curve (AUC-ROC), accuracy, precision, recall, F1 score, and respective macro-average metrics. A total of 1,798 enhanced CT scans met the inclusion criteria were included in this study. The dataset was randomly divided into a training dataset (n = 1618) and a test dataset (n = 180) with a ratio of 9:1. The DenseNet model demonstrated promising predictions for both CTSI and Atlanta classification-labeled CT scans, with accuracy greater than 0.7 and AUC-ROC greater than 0.8. Specifically, when trained with CT scans labeled using CTSI, the DenseNet model achieved good performance, with a macro-average F1 score of 0.835 and a macro-average AUC-ROC of 0.980. The findings of this study affirm the feasibility of employing CNN models to predict the severity of AP using enhanced CT scans.
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Pancreatitis , Humanos , Enfermedad Aguda , Pancreatitis/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Redes Neurales de la Computación , Curva ROC , Estudios RetrospectivosRESUMEN
Background: Centrosomal Protein 55 (CEP55) was initially described as a main participant in the final stage of cytokinesis. Further research identified CEP55 as a cancer-testis antigen (CTA) that is aberrantly expressed in different malignancies and a cancer vaccination candidate. The current study aimed to disclose the complete expression of CEP55, its effect on various malignancy prognoses, and its role in the tumor microenvironment. Methods: Transcriptional information regarding tumor and normal tissues, as well as externally validated and protein expression data were gathered from the Cancer Genome Atlas, Genotype-Tissue Expression project, Gene Expression Omnibus, and Human Protein Atlas. We examined the effect of CEP55 on tumor prognosis using Kaplan-Meier (KM) and univariate Cox regression analyses. In addition, we investigated the connections between CEP55 expression and hallmark cancer pathways, immune cell infiltration, and immune regulator expression across malignancies. We constructed and validated a CEP55-related risk model for hepatocellular carcinoma (HCC) and explored the correlations between CEP55 expression and HCC molecular subtypes. Finally, we investigated putative small-molecule drugs targeting CEP55 using a connectivity map (CMap) database and validated them using molecular docking analysis. Findings: CEP55 was aberrantly expressed in most cancers and revealed a prognostic value for several malignancies. Cancers with high CEP55 expression showed significantly enhanced cell cycle, proliferation, and immune-related pathways. For most malignancies, elevated CEP55 expression was associated with the infiltration of myeloid-derived suppressor cells (MDSCs) and Th2 cells. In addition, CEP55 expression was linked to immunomodulators and the potential prediction of immune checkpoint inhibitor (ICI) responses, and strongly associated with distinct molecular HCC subtypes, whereby the CEP55-based nomogram performed well in predicting short- and long-term HCC survival. Finally, we used connectivity map (CMap) and molecular docking analyses to discover three candidate small-molecule drugs that could directly bind to CEP55. Conclusion: CEP55 affected the occurrence and development of various cancers and possibly the regulation of the tumor immune microenvironment. Our findings suggest that CEP55 is a potential biomarker for prognosis and a powerful biomarker for ICI efficacy prediction.
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AIM: Nurse-led transitional care programmes (TCPs) have been shown to facilitate patient recovery in several illness settings, but its role among patients discharged with T-tubes remains uncertain. The aim of the study was to investigate the effects of a nurse-led TCP among patients discharged with T-tubes. DESIGN: This retrospective cohort study was conducted at a tertiary medical centre. METHODS: From January 2018 to December 2020, a total of 706 patients discharged with T-tubes after biliary surgery were included in the study. Patients were divided into a TCP group (n = 255) and a control group (n = 451) based on whether they participated in a TCP. The baseline characteristics, discharge readiness, self-care ability, transitional care quality and quality of life (QoL) were compared between the groups. RESULTS: Self-care ability and transitional care quality were significantly higher in the TCP group. Patients in the TCP group also exhibited improved QoL and satisfaction. The results suggest that the incorporation of a nurse-led TCP among patients discharged with T-tubes after biliary surgery is feasible and effective. No Patient or Public Contribution.
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Alta del Paciente , Cuidado de Transición , Humanos , Calidad de Vida , Rol de la Enfermera , Estudios RetrospectivosRESUMEN
Background and aims: Improved mortality prediction among intensive care unit (ICU) inpatients is a valuable and challenging task. Limited clinical data, especially with appropriate labels, are an important element restricting accurate predictions. Generative adversarial networks (GANs) are excellent generative models and have shown great potential for data simulation. However, there have been no relevant studies using GANs to predict mortality among ICU inpatients. In this study, we aim to evaluate the predictive performance of a variant of GAN called conditional medical GAN (c-med GAN) compared with some baseline models, including simplified acute physiology score II (SAPS II), support vector machine (SVM), and multilayer perceptron (MLP). Methods: Data from a publicly available intensive care database, the Medical Information Mart for Intensive Care III (MIMIC-III) database (v1.4), were included in this study. The area under the precision-recall curve (PR-AUC), area under the receiver operating characteristic curve (ROC-AUC), and F1 score were used to evaluate the predictive performance. In addition, the size of the dataset was artificially reduced, and the performance of the c-med GAN was compared in different size datasets. Results: The results showed that c-med GAN achieves the best PR-AUC, ROC-AUC, and F1 score compared with SAPS II, SVM, and MLP when training in the full MIMIC-III dataset. When the size of the dataset was reduced, the prediction performances of both MLP and c-med GAN were affected. However, the c-med GAN still outperformed MLP on smaller datasets and had less degradation. Conclusion: The prediction of in-hospital mortality based on the c-med GAN for ICU patients showed better performance than the baseline models. Despite some inadequacies, this model may have a promising future in clinical applications which will be explored by further research.
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Background and aims: Accurately predicting length of stay (LOS) is considered a challenging task for health care systems globally. In previous studies on LOS range prediction, researchers commonly pre-classified the LOS ranges, which were the same for all patients in the same classification, and then utilized a classifier for prediction. In this study, we innovatively aimed to predict the specific LOS range for each patient (the LOS range was different for each patient). Methods: In the modified deep neural network (DNN), the overall sample error (root mean square error (RMSE) method), the estimated sample error (ERRpred method), the probability distribution with different loss functions (Dispred_Loss1, Dispred_Loss2, and Dispred_Loss3 method), and the generative adversarial networks (WGAN-GP for LOS method) are used for LOS range prediction. The Medical Information Mart for Intensive Care III (MIMIC-III) database is used to validate these methods. Results: The RMSE method is convenient for LOS range prediction, but the predicted ranges are all consistent in the same batch of samples. The ERRpred method can achieve better prediction results in samples with low errors. However, the prediction effect is worse in samples with larger errors. The Dispred_Loss1 method encounters a training instability problem. The Dispred_Loss2 and Dispred_Loss3 methods perform well in making predictions. Although WGAN-GP for LOS method does not show a substantial advantage over other methods, this method might have the potential to improve the predictive performance. Conclusion: The results show that it is possible to achieve an acceptable accurate LOS range prediction through a reasonable model design, which may help physicians in the clinic.
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This study aimed to investigate whether mobile health (mHealth)-based transitional care, which utilized WeChat, could benefit patients undergoing hepatectomy. From January 2019 to December 2020, 807 patients who underwent hepatectomy in a tertiary care hospital were included in the study. Patients were divided into a transitional care group (TC group) (n = 238) and a control group (n = 569) based on whether they participated in mHealth-based transitional care, which utilized the WeChat application. Depending on the type of variables, t-tests, χ2 tests, and other statistical methods were used to compare differences between groups. Propensity score matching analysis was conducted for factors that differed in basic characteristics. After 1:1 matching, 238 patients were included in each group. Less readmission within 90 days of discharge, better quality of life, and higher satisfaction were found in the TC group both before and after matching (p < .05). This study showed the potential of applying mHealth-based transitional care among post-hepatectomy patients.
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Telemedicina , Cuidado de Transición , Humanos , Proyectos Piloto , Hepatectomía , Calidad de Vida , Telemedicina/métodosRESUMEN
BACKGROUND: Intra-abdominal hypertension (IAH) is an important risk factor for organ dysfunction, and it occurs in the early phase of severe acute pancreatitis (SAP). We have reported a novel step-up approach and shown the benefit of performing abdominal paracentesis drainage (APD) ahead of percutaneous catheter drainage (PCD) when treating Patients with SAP with fluid collections. This study aimed to evaluate the efficacy of APD in Patients with SAP complicated with IAH in the early phase. METHODS: In the present study, 206 AP patients complicated with IAH in the early phase were enrolled in hospital between June 2017 and December 2020. The patients were divided into two groups: 109 underwent APD (APD group) and 97 were managed without APD (non-APD group). We retrospectively compared the outcomes of the APD and non-APD groups for IAH treatment. The parameters including mortality, infection, organ failure, inflammatory factors, indications for further interventions, and drainage-related complications were observed. RESULTS: The demographic data and severity scores of the two groups were comparable. The mortality rate was lower in the APD group (3.7%) than in the non-APD group (8.2%). Compared with the non-APD group, the intra-abdominal pressure and laboratory parameters of the APD group decreased more rapidly, and the mean number of failed organs was lower. However, there was no significant difference in incidence of infections between the two groups. CONCLUSIONS: Application of APD is beneficial to AP patients. It significantly attenuated inflammation injury, avoided further interventions, and reduced multiple organ failure.
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Hipertensión Intraabdominal , Pancreatitis , Humanos , Pancreatitis/complicaciones , Pancreatitis/terapia , Paracentesis/efectos adversos , Hipertensión Intraabdominal/terapia , Hipertensión Intraabdominal/complicaciones , Estudios Retrospectivos , Enfermedad Aguda , Drenaje/efectos adversosRESUMEN
Accumulating studies have demonstrated critical roles of N6-methyladenosine (m6A) modification and long noncoding RNAs (lncRNAs) in the biological processes leading to occurrence, development and chemoresistance of cancers. However, the specific identities and functional roles of lncRNAs associated with m6A modification in hepatocellular carcinoma (HCC) remain elusive. In this study, eighty-two prognostic m6A-related lncRNAs (m6A-LncRNAs) were identified in HCC datasets. Patients with HCC were classified into three subtypes (C1, C2 and C3) based on the expression of the m6A-LncRNAs. The three subtypes showed significant differences in clinical features, immune and stromal infiltration signatures, and immunotherapy sensitivity. Subclass C1 was notable for high immune and stromal cell infiltration and active immune responses, low serum α-fetoprotein (AFP) levels and high sensitivity to immune checkpoint inhibitors (ICIs). Subclass C2 showed high metabolic activities and absence of immune infiltration with favorable prognosis. Subclass C3 was associated with an exhausted immune environment, high serum AFP and poor prognosis. Notably, subclass C3 displayed high expression of immune checkpoints but failed to respond to ICIs. Finally, 12 m6A-LncRNA signatures were identified for HCC classification and validated in an external dataset. This integrated analysis indicated that the interactions between m6A methylation and lncRNAs are involved in immune and stromal cell infiltration in HCC, and may provide novel insights into precision diagnostics as well as therapeutics for HCC patients.
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Objectives: This study aimed to develop a nomogram for predicting the risk of pressure injury (PI) in adult patients undergoing abdominal surgery and validate its effectiveness among these patients. Methods: This study retrospectively included 11,247 adult patients, who underwent abdominal surgery and postoperative supervision in ICU, in a tertiary care hospital in western China between January 2017 and December 2020. All datasets were extracted from the patient's medical records and randomly divided into the training cohort (8,997) and the validation cohort (2,250) by 8:2. The univariable logistic regression was used to select potentially relevant features. Then, multivariable logistic regression was also conducted and utilized to establish the nomogram. The nomogram was compared with the Braden scale for predicting PI in the validation cohort through the area under the curve (AUC) of the receiver operator characteristic (ROC) curve, Hosmer-Lemeshow (H-L) test, and decision curve analysis (DCA). Results: 873 (7.8%) patients suffered PIs. Logistic regression analysis showed that time of operation, weight, type of operation, albumin, and Braden scale score were independent risk factors for PI. A nomogram integrating five selected characteristics was constructed. The AUC of the ROC curve for the nomogram was 0.831, with a specificity of 85.2% and sensitivity of 63.7%. The AUC of the ROC curve for the Braden scale was 0.567, with a specificity of only 33.0%. The P-values of the H-L test were 0.45 (nomogram) and 0.22 (Braden scale), both indicating good calibration. The DCA also displayed that the nomogram had better predictive validity. Conclusion: Compared with the Braden scale, the nomogram showed a better predictive performance. This nomogram is informative and has the potential to better guide caregivers for risk stratification and prevention of PI, although it requires further validation.
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BACKGROUND: Jaundice is a major manifestation of posthepatectomy liver failure, a feared complication after hepatic resection. Herein, we report a case of posthepatectomy jaundice that was not caused by liver failure but by paroxysmal nocturnal hemoglobinuria (PNH)-induced hemolysis. CASE SUMMARY: A 56-year-old woman underwent right hepatectomy and biliary tract exploration surgery due to hepatic duct stones. Prior to surgery, the patient was mildly anemic. The direct antiglobulin test was negative. A bone marrow biopsy showed mild histiocyte hyperplasia. After surgery, the patient suffered a progressive increase in serum bilirubin. Meanwhile, the patient developed hemolytic symptoms after blood transfusion. She was ultimately diagnosed with PNH. PNH is a rare bone marrow failure disorder that manifests as complement-dependent intravascular hemolysis with varying severity. After steroid treatment, the patient's jaundice gradually decreased, and the patient was discharged on the 35th postoperative day. CONCLUSION: PNH-induced hemolysis is a rare cause of posthepatectomy jaundice. It should be suspected in patients having posthepatectomy hyperbilirubinemia without other signs of liver failure. Steroid therapy can be considered for the treatment of PNH in such cases.
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BACKGROUND: Several studies recommend that colonic hepatic flexure (CHF) should be mobilized preliminarily in minimally invasive pancreaticoduodenectomy (PD). However, there are little data to support that preferential mobilization of the CHF can positively affect the perioperative events of PD. We aimed to assess the effect of preferential mobilization of the CHF in PD. METHODS: A retrospective cohort study of patients who underwent PD was performed between 2016 and 2019. Clinical characteristics, operative data, and postoperative surgical complications were recorded. RESULTS: The study included 668 patients; 486 patients underwent open pancreaticoduodenectomy (OPD) and 182 patients underwent laparoscopic pancreaticoduodenectomy (LPD). Patients were divided into CHF-M (OPD, n=129; LPD, n=95) and conventional (OPD, n=357; LPD, n=87) groups according to preferential CHF mobilization. There were no differences between the groups regarding most demographics. Within patients who underwent OPD, decreased estimated blood loss (EBL) (251.2±146.4 vs. 307.3±173.5 mL, P<0.05) was observed in CHF-M group. Within patients who underwent LPD, operative time (328.7±66.3 vs. 406.5±85.5 min, P<0.001), EBL (166.8±96.4 vs. 271.8±130.7 mL, P<0.001), the incidence of clinically relevant pancreaticfistula (7.4% vs. 23.0%, P<0.05), and length of stay (12.3±5.1 vs. 16.0±7.4 d, P<0.05) were decreased in CHF-M group. Moreover, patients with high body mass index who underwent LPD showed more significant differences in operative time (336.0±67.7 vs. 431.9±79.1, P<0.001) and EBL (179.6±97.8 vs. 278.2±135.6, P<0.001) between groups. CONCLUSION: We first demonstrated that preferential mobilization of the CHF can facilitate PD. The patients who underwent minimally invasive surgery and the patients with high body mass index may benefit more from this technique.
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Laparoscopía , Neoplasias Pancreáticas , Colon Ascendente/cirugía , Humanos , Laparoscopía/métodos , Tiempo de Internación , Pancreatectomía/efectos adversos , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND: Fragility hip fracture (FHF) is a significant cause of morbidity and mortality in older adults. In 2018, Best Practice Nursing Care Standards for Older Adults with Fragility Hip Fracture (NSOF) were released by The International Collaboration of Orthopaedic Nursing (ICON). However, there are only limited clinical data about the application of this standard in clinical practice in China. AIMS: To determine the clinical practice effect of the NSOF. METHODS: A retrospective single-centre cohort study was performed from January 2016 to June 2020. Patients were divided into the standardized nursing care group (SN group) and the conventional nursing care group (CN group) depending on whether they were cared for according to the NSOF criteria. The propensity score matched (PSM) analysis was conducted in this study. The perioperative and follow-up outcomes between the two groups were analyzed. RESULTS: A total of 204 patients diagnosed with FHF were included in the study. After a 1:1 matching, 56 cases were identified in the SN group as well as the CN group. Patients in the SN group had significantly shorter preoperative wait times for surgery (17.4 ± 4.6 vs. 24.4 ± 7.6 h, p < 0.05) and a higher proportion of individuals performing exercise within 24 h after surgery (94.6% vs. 66.1%, p < 0.05). Notably, patients in the SN group also had a significantly shorter length of stay than those in the CN group (9.4 ± 3.1 vs. 14.2 ± 5.1 days, p < 0.05). At the 6-month follow-up, the incidence of refracture was significantly lower (3.6% vs. 14.3%, p < 0.05), and the timed up and go mobility index was improved in the SN group compared to the CN group (20.3 ± 1.7 vs. 24.6 ± 2.2 s, p < 0.05). CONCLUSION: This study showed that application of the NSOF resulted in a significant improvement in the treatment of older adults patients with FHF.
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Fracturas de Cadera , Nivel de Atención , Anciano , Estudios de Cohortes , Fracturas de Cadera/cirugía , Humanos , Puntaje de Propensión , Estudios RetrospectivosRESUMEN
BACKGROUND: There are few reports about the effect of glucocorticoids in the treatment of acute pancreatitis in humans. This study aims to evaluate the effect of glucocorticoids in the treatment of acute pancreatitis by propensity score matching analysis. RESULTS: Acute pancreatitis patients admitted between 2014 and 2019 were collected from the database and analyzed. Included patients were divided into the glucocorticoids-used group (GC group) and the non-glucocorticoids-used group (NGC group) according to whether glucocorticoids were used. A total of 818 eligible patients were included in the final analysis. Seventy-six patients were treated with glucocorticoids, and 742 patients were treated without glucocorticoids. Before propensity score matching, the triglyceride levels (38.2 ± 18.5 vs. 20.2 ± 16.8, P < 0.05) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (7.1 ± 2.5 vs. 4.5 ± 2.1, P < 0.05) at admission were significantly higher in the GC group than in the NGC group. The incidence of multi-organ failure (33.3% vs. 11.9%, P < 0.05) was significantly higher in the GC group than in the NGC group. Patients in the GC group showed a positive balance of fluid intake and output over 72 h. After 1:1 propensity score matching, 59 patients from each group (GC and NGC) were included in the analysis. There were no significant differences in age, sex, body mass index, triglycerides, or APACHE II scores between the two groups (P > 0.05), and the patients' clinical outcomes were reversed. The proportion of patients with organ failure (40.7% vs. 52.5%, p < 0.05) and multi-organ failure (35.0% vs. 67.7%, P < 0.05) was significantly lower in the GC group than in the NGC group. Furthermore, patients in the GC group had significantly shorter lengths of hospital stay (12.9 ± 5.5 vs. 16.3 ± 7.7, P < 0.05) and costs (25,348.4 ± 2512.6vs. 32,421.7 ± 2813.3, P < 0.05) than those in the NGC group. CONCLUSIONS: This study presents preliminary confirmation of the beneficial effect of glucocorticoids in the treatment of acute pancreatitis. More high-quality prospective studies are needed in the future.
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Glucocorticoides , Pancreatitis , APACHE , Enfermedad Aguda , Glucocorticoides/uso terapéutico , Humanos , Pancreatitis/tratamiento farmacológico , Puntaje de PropensiónAsunto(s)
Drenaje/métodos , Mucosa Intestinal/cirugía , Pancreatitis/cirugía , Paracentesis/métodos , Enfermedad Aguda , Animales , Epoprostenol/sangre , Mucosa Intestinal/irrigación sanguínea , Mucosa Intestinal/lesiones , Microcirculación , Pancreatitis/sangre , Pancreatitis/patología , Ratas , Índice de Severidad de la Enfermedad , Tromboxano A2/sangreRESUMEN
Acute pancreatitis (AP), a kind of common acute abdominal disease and typical chemical inflammation, is commonly caused by pancreatin digestion of the pancreas and surrounding tissues. The gene for phosphate and tension homology deleted on chromosome ten (PTEN) is a tumor suppressor that regulates numerous cellular processes. In the present study, we have elaborately investigated the effect of PTEN on the alleviating of AP and its underlying mechanisms. Firstly, we demonstrated an up-regulation of PTEN in the pancreatic tissues from AP rats by immunochemistry, qRT-PCR and western-blot assays. Subsequently, cellular experiments exhibited that PTEN has a significant inhibition effect on the proliferation, invasion and migration of AP cells. Further underlying mechanism studies showed that the growth of AP cells was mainly restrained by PTEN in the G1 phase through activation of the Wnt/ß-catenin pathway, which can be demonstrated by the down-regulation of various pro-inflammatory cytokines such as IL-6, IL-10, TNF and IL-1ß. Taking these results together, we can draw the conclusion that PTEN plays a significant role in suppressing the inflammation, viability and motility of acute pancreatitis and could be a potential target for AP therapies.
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BACKGROUND: Liver cancer stem cells (LCSCs) are the key factors for cancer metastasis, recurrent, and drug resistance. LCSCs are originated from either hepatocytes dedifferentiation or differentiation arresting of liver normal stem cells (LNSCs). Differentiation-inducing therapy is a novel strategy in solid tumors. Furthermore, Notch signaling pathway has been proved to play important role in the process of hepatocytes differentiation. In previous study, a malignant transformation cellular model of LNSCs has been built up, and in this study we are trying to illustrate whether inhibition of Notch can reverse this malignant tendency and drive these malignant cells back to differentiate into mature hepatocytes. RESULTS: Inhibition of Notch signaling pathway can down-regulate the stemness-related cancer markers, lower the proliferative status, alleviate the invasive characteristic, or attenuate the metastasis tendency. What is more, it can help the malignantly transformed cells to regain the mature hepatic function of glucagon synthesis, urea metabolism, albumin production, and indocyanine-green (ICG) clearance. MATERIALS AND METHODS: HOX transcript antisense RNA (HOTAIR) expression was enhanced in LNSCs via lentivirus transduction to set up the malignant transformation cellular model. Then, a Notch inhibitor was applied to induce malignantly transformed cells differentiate into mature hepatocytes, and malignant abilities of proliferation, invasiveness, tumorigenesis as well as mature hepatocyte function were observed and compared. CONCLUSIONS: The data demonstrate that the anti-tumor effects of Notch inhibition may lie not only on killing the cancer cells or LCSCs directly, it can also induce the LCSCs differentiation into mature hepatocytes via mesenchymal-epithelial transition (MET) progress or downgrade the malignancy.
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BACKGROUND The correlation between sham feeding and acute pancreatitis (AP) has only been examined in limited studies. We aimed to investigate the efficacy and safety of sham feeding in the early stage of AP. MATERIAL AND METHODS A randomized controlled clinical trial was performed. Equal groups of AP patients were recruited. Patients in the sham feeding group received chewing gum 4 times a day after admission. All patients in the trial received standard treatment consistent with the guidelines for AP. The primary outcomes were mortality, length of stay (LOS), and medical expenses. Secondary outcomes were the incidence of complications and other adverse events, return of gastrointestinal function, the details of enteral nutrition and intra-abdominal pressure. RESULTS From May 2014 to December 2015, a total of 204 patients were recruited. The LOS and hospital costs in the sham feeding group were reduced, although mortality was equivalent between groups. The return of gastrointestinal function occurred earlier in the sham feeding group, with no complications related to gum chewing. CONCLUSIONS Sham feeding with chewing gum is safe and efficacious in the early stage of AP.