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Cholangiocarcinoma (CCA) displays enhanced glycolysis, pivotal for fulfilling the heightened energy demands intrinsic to its malignant progression. Recent research has indicated that endogenous glycogen rather than exogenous glucose acts as the major carbon source for glycolysis, highlighting the need to better understand the regulation of glycogen homeostasis in CCA. Here, through comprehensive integrative analysis, we identified that glycogen phosphorylase brain form (PYGB), the main enzyme involved in glycogen homeostasis, was markedly upregulated in CCA tissues, serving as an independent prognostic indicator for human CCA patients. Moreover, elevated PYGB expression potentiated cholangiocarcinogenesis and augmented CCA cell proliferation in both organoid and xenograft models. Hypoxia stimulated PYGB activity in a phosphoglycerate kinase 1 (PGK1)-dependent manner, leading to glycogenolysis and the subsequent release of glucose-6-phosphate (G6P) and thereby facilitating aerobic glycolysis. Notably, a virtual screening pinpointed the beta-blocker carvedilol as a potent pharmacological inhibitor of PYGB that could attenuate CCA progression. Collectively, these findings position PYGB as a promising prognostic biomarker and therapeutic target for CCA.
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Background: Distal malignant biliary obstruction (DMBO) can result in obstructive jaundice. Endoscopic ultrasound- (EUS-) guided biliary drainage (EUS-BD) has been an alternative for DMBO after failed ERCP. Aim: To compare the efficacy and safety between antegrade and transluminal approaches in patients with unresectable DMBO when ERCP failed. Methods: Patients with DMBO leading to obstructive jaundice after failed ERCP were enrolled in this study. We retrospectively evaluated the safety and efficacy between EUS-guided transluminal stenting (TLS group) and antegrade stenting (AGS group). Results: 82 patients were enrolled, of which 45 patients were in TLS group and 37 in AGS group. There were no statistical differences in the malignancy type, baseline common bile duct diameter, total bilirubin level, reason for EUS-BD, and history of biliary drainage between TLS and AGS groups. The technical success rate was statistically higher in TLS group than in AGS group (97.8 vs. 81.1%, P = 0.031). There were no statistical differences in clinical success rate, procedure-related adverse events, stent migration rate, stent dysfunction rate, reintervention rate, and overall patient survival time between TLS and AGS groups. The median time to stent dysfunction or patient death in TLS and AGS groups was 53 and 81 days, respectively (P = 0.017). Conclusions: Although AGS had a lower technical success rate than TLS, it was superior to TLS in stent patency in patients with DMBO.
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BACKGROUND: Endoscopic visualization of gallbladder lesions by the traditional peroral cholangioscopy (POCS) during the endoscopic retrograde cholangiopancreatography process is challenging. In the present study, we evaluated the feasibility of a newly designed POCS with an ultrafine outer diameter that facilitates gallbladder visualization. METHODS: The novel POCS was designed and manufactured with an outer diameter of 7 French and achieved extremely high performance. The feasibility of this novel POCS for gallbladder observation was assessed in our center between April 2022 and January 2023. The primary outcome was technical success. RESULTS: A total of 16 patients (64.6 ± 18.1 years, 9 males) who underwent novel ultrafine POCS inspection for gallbladder visualization were included. Technical success was achieved in 14 of 16 cases (87.5%); the main reasons for the two unsuccessful inspections were the presence of cystic duct strictures. A total of 1 adverse event occurred, for an overall rate of 6.3%, and there were no serious adverse events during the follow-up. CONCLUSIONS: The results suggest that endoscopic visualization of the gallbladder using the novel ultrafine POCS is feasible. The device is expected to provide a new direction for the management of gallbladder disorders in the future.
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Lithium compounds, a classic class of metal complex medicine that target GSK 3ß and are widely known as mood-stabilizer, have recently been reported as potential anti-tumor drugs. The objective of this investigation was to explore the anticancer potential of lithium chloride (LiCl) and elucidate its mode of action in pancreatic cancer cells. The MTT, colony formation, and Edu assay were used to evaluate the impact of LiCl on pancreatic cancer cell proliferation. Various methods were employed to investigate the anti-tumor activity of LiCl and its underlying mechanisms. Cell cycle analysis and apoptosis detection assays were utilized for in vitro experiments, while the orthotopic pancreatic cancer mouse model was employed to evaluate the effectiveness of LiCl treatment in vivo. Furthermore, the impact of LiCl on the proliferation of patient-derived organoids was also studied. The results demonstrated that LiCl inhibited the proliferation of pancreatic cancer (PC) cells, induced G2/M phase arrest, and activated apoptosis. Notably, the triggering of endoplasmic reticulum (ER) stress by LiCl was observed, leading to the activation of the PERK/CHOP/GADD34 pathway, which subsequently promoted apoptosis in PC cells. In the future, Lithium compounds could become an essential adjunct in the treatment of human pancreatic cancer.
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Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease refractory to all targeted and immune therapies. However, our understanding of PDAC microenvironment especially the metastatic microenvironment is very limited partly due to the inaccessibility to metastatic tumor tissues. Here, we present the single-cell transcriptomic landscape of synchronously resected PDAC primary tumors and matched liver metastases. We perform comparative analysis on both cellular composition and functional phenotype between primary and metastatic tumors. Tumor cells exhibit distinct transcriptomic profile in liver metastasis with clearly defined evolutionary routes from cancer cells in primary tumor. We also identify specific subtypes of stromal and immune cells critical to the formation of the pro-tumor microenvironment in metastatic lesions, including RGS5+ cancer-associated fibroblasts, CCL18+ lipid-associated macrophages, S100A8+ neutrophils and FOXP3+ regulatory T cells. Cellular interactome analysis further reveals that the lack of tumor-immune cell interaction in metastatic tissues contributes to the formation of the immunosuppressive microenvironment. Our study provides a comprehensive characterization of the transcriptional landscape of PDAC liver metastasis.
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Carcinome du canal pancréatique , Tumeurs du foie , Tumeurs du pancréas , Humains , Transcriptome , Microenvironnement tumoral/génétique , Tumeurs du pancréas/génétique , Tumeurs du foie/génétique , Carcinome du canal pancréatique/génétique , Immunosuppresseurs , Tumeurs du pancréasRÉSUMÉ
Background: Readmission shortly after discharge is indicative of an increased disease severity for patients with ulcerative colitis (UC) and ineffectiveness to medical therapy, which may contribute to a dismal prognosis. Objectives: This study aimed to explore prognostic variables with a nomogram to predict unplanned UC-related readmission within 1 year after discharge. Design: A retrospective cohort study. Methods: Electronic medical records of all UC patients treated at our center between 1 January 2014 and 31 June 2021 were reviewed. A comprehensive analysis of various characteristics, such as demographics, comorbidities, medical history, follow-up appointments, admission endoscopy, histopathologic features, etc., was used to determine the primary end point, which was unplanned UC-related calendar year readmission. Results: We found that the unplanned UC-related readmission rate within 1 year was 20.8%. In multivariable cox analysis, the predictors of the Elixhauser comorbidity index [Hazard ratio (HR): 3.50, 95% confidence interval (CI): 1.93-6.37], regular follow-up (HR: 0.29, 95% CI: 0.16-0.53), any history of corticosteroid use (HR: 3.38, 95% CI: 1.83-6.27), seral level of C-reactive protein (HR: 1.01, 95% CI: 1.00-1.02), and the UC endoscopic index of severity (HR: 1.29, 95% CI: 1.05-1.57) independently predicted calendar year readmission after discharge. The established nomogram had a consistently high accuracy in predicting calendar year readmission in the training cohort, with a concordance index of 0.784, 0.825, and 0.837 at 13, 26, and 52 weeks, respectively, which was validated in both the internal and external validation cohorts. Therefore, UC patients were divided into clinically low-, high-, and extremely high-risk groups for readmission, based on the calculated score of 272.5 and 378. Conclusion: The established nomogram showed good discrimination and calibration powers in predicting calendar year readmission in high-risk UC patients, who may need intensive treatment and regular outpatient visits.
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BACKGROUND AND AIMS: It is crucial to accurately determine malignant biliary strictures (MBSs) for early curative treatment. This study aimed to develop a real-time interpretable artificial intelligence (AI) system to predict MBSs under digital single-operator cholangioscopy (DSOC). METHODS: A novel interpretable AI system called MBSDeiT was developed consisting of 2 models to identify qualified images and then predict MBSs in real time. The overall efficiency of MBSDeiT was validated at the image level on internal, external, and prospective testing data sets and subgroup analyses, and at the video level on the prospective data sets; these findings were compared with those of the endoscopists. The association between AI predictions and endoscopic features was evaluated to increase the interpretability. RESULTS: MBSDeiT can first automatically select qualified DSOC images with an area under the curve (AUC) of .963 and .968 to .973 on the internal testing data set and the external testing data sets, and then identify MBSs with an AUC of .971 on the internal testing data set, an AUC of .978 to .999 on the external testing data sets, and an AUC of .976 on the prospective testing data set, respectively. MBSDeiT accurately identified 92.3% of MBSs in prospective testing videos. Subgroup analyses confirmed the stability and robustness of MBSDeiT. The AI system achieved superior performance to that of expert and novice endoscopists. The AI predictions were significantly associated with 4 endoscopic features (nodular mass, friability, raised intraductal lesion, and abnormal vessels; P < .05) under DSOC, which is consistent with the endoscopists' predictions. CONCLUSIONS: The study findings suggest that MBSDeiT could be a promising approach for the accurate diagnosis of MBSs under DSOC.
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Intelligence artificielle , Laparoscopie , Humains , Sténose pathologique/diagnostic , Sténose pathologique/étiologie , Études prospectives , Aire sous la courbeRÉSUMÉ
Background and Aims: Currently sedation is a common practice in colonoscopy to reduce pain of patients and improve the operator satisfaction, whereas its impact on examination quality, especially adenoma detection rate (ADR) is still controversial. Thus, we aimed to investigate the association of sedation with ADR. Methods: Consecutive patients receiving colonoscopy between January 2017 and January 2020 at the Nanjing Drum Tower Hospital, Nanjing, China, were collected. Univariate and multivariate logistic regression models were performed to investigate the association between sedation and ADR. Subgroup analysis and propensity score matching (PSM) analysis, as sensitivity analysis, were performed to validate the independent effect. Results: The ADR was significantly higher in cases with sedation (ADR: 36.9% vs. 29.1%, odds ratio [OR]: 1.42, 95% confidence interval [CI]: 1.31-1.55, P < 0.001). Multivariate analysis showed that the sedation was an independent factor associated with ADR (OR: 1.49, 95% CI: 1.35-1.65, P < 0.001). The effect was consistent in subgroup analyses (P > 0.05) and PSM analysis (ADR: 37.6% vs. 29.1%, OR: 1.47, 95% CI: 1.33-1.63, P < 0.001). Conclusion: Sedation was associated with a higher polyp and ADR s during colonoscopy, which can promote the quality of colonoscopy.
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Given the metastasis-promoting effect of pancreatic ductal adenocarcinoma (PDAC)-derived exosomes through activation of fibrotic premetastatic niches, targeting and intervening in premetastatic organs to inhibit distant metastasis have challenged researchers and clinicians. Herein, a self-biomimetic drug delivery system based on exosomes derived from PDAC (PF@PCCEs) was constructed to precisely deliver an antifibrotic drug (pirfenidone, PF) to fibrotic premetastatic organs. First, PDAC-derived exosomes were confirmed to remarkably promote liver fibrosis. Then the prepared PF@PCCEs were actively internalized by HSCs (hepatic stellate cells) and subsequently alleviated the activation of HSCs. Delivery of PF to the premetastatic liver affected the niche suitable for the colonization of circulating tumour cells, further suppressing liver metastasis of PDAC. Thus, the strategy for intervening in the formation of fibrotic premetastatic niches to inhibit liver metastasis of PDAC using PF@PCCEs might offer inspiration for the treatment of tumour metastasis.
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Carcinome du canal pancréatique , Exosomes , Tumeurs du foie , Tumeurs du pancréas , Humains , Lignée cellulaire tumorale , Carcinome du canal pancréatique/traitement médicamenteux , Carcinome du canal pancréatique/anatomopathologie , Tumeurs du pancréas/traitement médicamenteux , Tumeurs du pancréas/anatomopathologie , Tumeurs du foie/anatomopathologie , Cirrhose du foie/traitement médicamenteux , Cirrhose du foie/anatomopathologie , Tumeurs du pancréasRÉSUMÉ
Dietary interventions, including dietary ingredients, nutrients and probiotics, exert anti-inflammatory effects in ulcerative colitis (UC). Our previous study showed that Akkermansia muciniphila (Akk), a promising probiotic, could protect against colitis via the regulation of the immune response. However, whether it can restore aberrant tryptophan (Trp) metabolism during colitis remains unclear. In this study, untargeted serum metabolomics of patients with UC and colitis mice showed that Trp metabolism was activated, which was confirmed by quantification of Trp metabolites from a validation cohort and animal study. Integrative analysis of faecal metagenomes and serum metabolomes revealed significant associations between Akk and three Trp metabolites. Live Akk, pasteurised Akk and Amuc_1100 failed to restore the reduction in Trp metabolites involved in the serotonin pathway in colitis mice. However, live Akk, pasteurised Akk and Amuc_1100 increased kynurenine (Kyn) but decreased 2-picolinic acid (PIC) levels and the PIC/Kyn ratio without regulating any of the genes involved in Trp metabolism, suggesting that they could suppress the Kyn pathway (KP) independent of colon tissue. In addition, they could significantly restore the enrichment of Trp metabolism mediated by faecal microbiota. Specifically, live Akk, pasteurised Akk and Amuc_1100 could significantly offset the reduction in indoleacetic acid (IAA) levels. Pasteurised Akk significantly elevated the serum levels of indole acrylic acid (IA). In addition, live Akk, pasteurised Akk and Amuc_1100 could upregulate aryl hydrocarbon receptor (AhR) targeted genes, including CYP1A1, IL-10 and IL-22, suggesting that Akk could activate AhR signaling by regulating Trp metabolism, thereby attenuating colonic inflammation.
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Protéines de la membrane externe bactérienne/pharmacologie , Rectocolite hémorragique/traitement médicamenteux , Probiotiques/pharmacologie , Tryptophane/métabolisme , Adulte , Akkermansia (genre) , Animaux , Colite/traitement médicamenteux , Colite/métabolisme , Rectocolite hémorragique/sang , Rectocolite hémorragique/métabolisme , Fèces/microbiologie , Microbiome gastro-intestinal/effets des médicaments et des substances chimiques , Humains , Cynurénine/métabolisme , Mâle , Métabolomique/méthodes , Métagénomique/méthodes , Souris , Souris de lignée C57BL , Adulte d'âge moyen , Acides picoliniques/métabolisme , Sérotonine/métabolismeRÉSUMÉ
The effect of projectile nose shape on the ballistic performance of the ultra-high molecular weight polyethylene (UHMWPE) composite was studied through experiments and simulations. Eight projectiles such as conical, flat, hemispherical, and ogival nose projectiles were used in this study. The deformation process, failure mechanisms, and the specific energy absorption (SEA) ability were systematically investigated for analyzing the ballistic responses on the projectile and the UHMWPE composite. The results showed that the projectile nose shape could invoke different penetration mechanisms on the composite. The sharper nose projectile tended to shear through the laminate, causing localized damage zone on the composite. For the blunt nose projectile penetration, the primary deformation features were the combination of shear plugging, tensile deformation, and large area delamination. The maximum value of specific energy absorption (SEA) was 290 J/(kg/m2) for the flat nose projectile penetration, about 3.8 times higher than that for the 30° conical nose projectile. Furthermore, a ballistic resistance analytical model was built based on the cavity expansion theory to predict the energy absorption ability of the UHMWPE composite. The model exhibited a good match between the ballistic resistance curves in simulations with the SEA ability of the UHMWPE composite in experiments.
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Homeostasis of microelements in organisms is vital for normal metabolism. In plants, the cation diffusion facilitator (CDF) protein family, also known as metal tolerance proteins (MTPs), play critical roles in maintaining trace metal homeostasis. However, little is known about these proteins in wheat. In this study, we characterized the MTP family of Triticum urartu, the donor of 'A' genome of Triticum aestivum, and analysed their phylogenetic relationships, sequence signatures, spatial expression patterns in the diploid wheat, and their transport activity when heterologously expressed. Nine MTPs were identified in the T. urartu genome database, and were classified and designated based on their sequence similarity to Arabidopsis thaliana (Arabidopsis) and Oryza sativa MTPs. Phylogenetic and sequence analyses indicated that the triticum urartu metal tolerance protein (TuMTP)s comprise three Zn-CDFs, two Fe/Zn-CDFs, and four Mn-CDFs; and can be further classified into six subgroups. Among the TuMTPs, there are no MTP2-5 and MTP9-10 counterparts but two MTP1/8/11 orthologs in relation to AtMTPs. It was also shown that members of the same cluster share similar sequence characteristic, i.e. number of introns, predicted transmembrane domains, and motifs. When expressed in yeast, TuMTP1 and TuMTP1.1 conferred tolerance to Zn and Co but not to other metal ions; while TuMTP8, TuMTP8.1, TuMTP11, and TuMTP11.1 conferred tolerance to Mn. When expressed in Arabidopsis, TuMTP1 localized to the tonoplast and significantly enhanced Zn and Co tolerance. TuMTPs showed diverse tissue-specific expression patterns. Taken together, the closely clustered TuMTPs share structural features and metal specificity but play diverse roles in the homeostasis of microelements in plant cells.
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Transporteurs de cations/métabolisme , Régulation de l'expression des gènes végétaux , Métaux/métabolisme , Phylogenèse , Protéines végétales/métabolisme , Triticum/métabolisme , Séquence d'acides aminés , Arabidopsis/génétique , Arabidopsis/métabolisme , Transporteurs de cations/génétique , Oryza/génétique , Oryza/métabolisme , Protéines végétales/génétique , Saccharomyces cerevisiae/génétique , Saccharomyces cerevisiae/métabolisme , Similitude de séquences , Triticum/génétique , Triticum/croissance et développementRÉSUMÉ
BACKGROUND: A few models have been proposed for the prediction of the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP), but many include factors that are not assessed routinely. Herein, we intend to develop and validate a predictive model for the occurrence of PEP. METHODS: Data of patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) from January 01, 2016 to May 16, 2019 (training set and internal test set) and from May 17, 2019 to December 25, 2019 (external test set) were retrospectively collected. The performance of the model was validated in the two validation cohorts. RESULTS: A total of 342 patients were included for the external test set, and 47 (13.7%) developed PEP. The variables included in the scoring system were gastrectomy history, high direct bilirubin (DBIL), high albumin (ALB), villous type of papillary orifice, nodular type of papillary orifice, pancreatic guidewire passages, precut sphincterotomy, and high operator experience. A total score >5 indicated high risk. In the external test set, the area under the curve (AUC) was 0.718, the sensitivity was 0.723, and the specificity was 0.676. In the external test set, the probability of PEP was 6.1%, 17.0%, and 37.5% in patients with low (<0), moderate (0-5), and high (>5) risk scores, respectively. CONCLUSIONS: This study established a scoring system for predicting the risk of PEP using routinely measured clinical variables. Its application in routine work warrants further investigation.
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Background and study aims Gastric outlet obstruction (GOO) is common in the late stage of many malignant tumors of the digestive system. Endoscopic ultrasound (EUS)-guided gastroenterostomy (EUS-GE) is commonly used for palliative treatment of malignant GOO. The objective of this study was to investigate the safety, efficacy, and prognosis of EUS-GE in treatment of malignant GOO in Chinese patients. Patients and methods This was a retrospective, single-center study with 36 consecutive patients with malignant GOO who were treated with EUS-GE. The main outcome measures were technical success rate, clinical success rate, incidence of adverse events (AEs), and median survival time. Results A total of 36 patients with malignant GOO underwent double-balloon-assisted EUS-GE between March 2017 and June 2019 in our hospital. GOO occurred mainly in elderly men (mean age 69.0 years, M:F 0.89). The most common etiology of GOO was pancreatic cancer (41.7â%). The most common obstruction site was the second part of the duodenum (63.9â%). The technical success rate was 100â% (36/36). The clinical success rate was 94.4â% (34/36). Median time for the total procedure was 52 minutes (range 34â-â156âmin). Median time for determination of puncture site was 20 minutes (range 15â-â28âmin). Median time between puncture and successful delivery of the stent was 38 minutes (range 19â-â128âmin). The GOOSS score was 0.2 before EUS-GE. The GOO Scoring System (GOOSS) score was 2.2 at 15 days after the EUS-GE ( P â=â0.001). The GOOSS score was still higher than 2 during a median follow-up period of 89 days. AEs were observed in nine patients (25.0â%) and 13 total AEs occurred. One patient died as a result of delayed stent migration and bleeding. Mean length of hospital stay was 5.8â±â4.7 days. The median survival period was 103 days. The rate of GOO recurrence was 2.7â% (1/36). Conclusion EUS-GE was associated with increased safety and efficacy for treatment of malignant GOO in Chinese Mainland.
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Laparoscopic cholecystectomy is the routine method to treat gallbladder polyps. Nowadays, endoscopic ultrasound (EUS)-guided cholecystostomy as a bridge for per-oral transmural endoscopic resection of gallbladder polyps is introduced because preservation of gallbladder is increasingly getting attention. The aim of our study was to evaluate the approach in the treatment of patients with gallbladder polyps and symptomatic gallstones.EUS-guided cholecystostomy with the placement of a lumen-apposing metal stent (LAMS) was performed for those patients with accompanying gallbladder polyps and symptomatic gallstones. Several days after the cholecystostomy with LAMS, a gastroscope was introduced into the gallbladder to remove gallbladder polyps.All patients were successfully performed with the procedures of EUS-guided cholecystoduodenostomy (nâ=â3) or cholecystogastrostomy (nâ=â1) and endoscopic resection of gallbladder polyps. One patient experienced severe peritonitis. During the follow-up at 3 months, 1 patient was performed with laparoscopic cholecystectomy because ultrasonography examination showed the reappeared gallstones. No stone recurrence was found in other patients. During the follow-up of 3 to 15 months, no polyp recurrence was found in all the patients.The approach is novel for performing EUS-guided gallbladder fistulization, which can subsequently allow procedures of per-oral transmural endoscopic resection of gallbladder polyps to avoid cholecystectomy in the patients with gallbladder polyps and gallstones. However, further studies are needed before clinical recommendation because of the complications and stone recurrence.
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Cholécystostomie/méthodes , Endosonographie/méthodes , Vésicule biliaire/imagerie diagnostique , Polypes/chirurgie , Adulte , Anastomose chirurgicale/méthodes , Duodénostomie/méthodes , Femelle , Études de suivi , Vésicule biliaire/anatomopathologie , Calculs biliaires/chirurgie , Gastrostomie/méthodes , Humains , Mâle , Métaux , Adulte d'âge moyen , Études rétrospectives , Endoprothèses , Résultat thérapeutique , Échographie interventionnelle/instrumentationRÉSUMÉ
Submucosal glands (SMGs) present throughout human esophagus with clusters at either the upper third or lower third of the organ. SMGs tend to atrophy with age, and neoplasms arising in these glands are rare. In order to bring convenience to diagnosis, we summarize the histopathologic characteristics of all esophageal submucosal gland tumors (SGTs). Due to the morphological similarity, the nomenclature of salivary tumors is adopted for SGTs. However, there is great confusion about the definition and histogenesis of these tumors, especially the malignant subtypes. In the literature, esophageal mucoepidermoid carcinoma and adenoid cystic carcinoma usually adjoin the surface squamous epithelium and coexist with intraepithelial neoplasia or invasive squamous cell carcinoma (SCC). In addition, the typical gene alterations of salivary tumors have not been reported in these SGTs. Therefore, we propose to apply stringent diagnostic criteria to esophageal SGTs so as to exclude mimickers that are SCCs with various degree of SMG differentiation.
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Tumeurs de l'oesophage/anatomopathologie , Oesophage/anatomopathologie , Tumeurs épithéliales épidermoïdes et glandulaires/anatomopathologie , Sujet âgé de 80 ans ou plus , Atrophie/anatomopathologie , Épithélioma in situ/anatomopathologie , Carcinome adénoïde kystique/diagnostic , Carcinome mucoépidermoïde/diagnostic , Carcinome épidermoïde/diagnostic , Humains , Kératines/métabolisme , Mâle , Mucine 5B/métabolisme , Tumeurs épithéliales épidermoïdes et glandulaires/métabolisme , Études rétrospectivesRÉSUMÉ
PURPOSE: Patients with inflammatory bowel disease (IBD) frequently suffer from venous thromboembolic events, and the risk of thromboembolism increases along with disease activity. This study was conducted to discover novel thrombophilic markers using thromboelastography (TEG) and to evaluate the relation between the predisposing factors and the activity of disease in Chinese patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Thirty-four patients with CD, 29 patients with UC, and 53 healthy volunteers were enrolled into this study. Blood levels of R, K, α Angle, G, maximal amplitude (MA), and LY30 with TEG were determined. RESULTS: Mean values of R, K, α Angle, G, and MA were significantly different in patients with CD and UC compared with the healthy individuals. Patients with active CD had different K, α Angle, G, and MA levels compared with patients in remission (P < 0.05, P < 0.001, P < 0.001, and P < 0.001). Levels of R, α Angle, G, and MA were also significantly different in active UC patients compared with those in remission (P < 0.01, P < 0.001, P < 0.001, and P < 0.001). Except for the G level in the CD group, differences in all TEG levels between healthy individuals and IBD patients in remission were not statistically significant. No statistical differences were observed in LY30 among patients with active phase, patients in remission, and the healthy individuals. CONCLUSION: Thrombophilic defects are common in Chinese patients with IBD, and TEG can be considered a new direction to anticoagulant thromboprophylaxis in IBD.
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Tumeurs des canaux biliaires , Cholangiocarcinome , Ictère rétentionnel , Tumeurs des canaux biliaires/complications , Conduits biliaires intrahépatiques , Cholangiocarcinome/complications , Diagnostic différentiel , Humains , Ictère rétentionnel/étiologie , Veine porte/imagerie diagnostiqueRÉSUMÉ
BACKGROUND: The transcription factor, E2F transcription factor 3 (E2F3), has been proved to modulate metastasis in multiple human cancers. The present study was aimed to expound the function and specific mechanism of E2F3 in gastric cancer (GC) progression. MATERIALS AND METHODS: The expression of E2F3, microRNA-152 (miR-152) and PLK1 (polo-like kinase 1) in GC cell lines was detected by quantitative RT-PCR and Western blot. The roles of E2F3 and miR-152 in GC metastasis were classified using gain-of-function and loss-of-function assays. The miRNAs directly targeting E2F3 were identified by bioinformatics analysis and luciferase reporter experiment. Chromatin immunoprecipitation was carried out to reveal the correlation between E2F3 and PLK1. RESULTS: E2F3 expression was frequently up-regulated in GC tissues, and its high expression might imply poor prognosis. Downregulation of E2F3 restrained GC migration and invasion in vitro and in vivo. Interestingly, we proved that miR-152 was an upstream regulator of E2F3. Moreover, miR-152 reduced E2F3 expression by directly targeting its 3'-UTR, and then modulated GC metastasis via polo-like kinase 1 (PLK1) mediated protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) signals. CONCLUSION: E2F3 plays a crucial role in GC progression and the newly discovered miR-152/E2F3/PLK1 axis provides a new underlying target for therapy of metastasis in GC patients.
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BACKGROUND: Endoscopic transpapillary cannulation of the gallbladder is useful but challenging. This study aimed to investigate cystic duct anatomy patterns, which may guide cystic duct cannulation. METHODS: A total of 226 patients who underwent endoscopic transpapillary cannulation of the gallbladder were analyzed retrospectively. RESULTS: According to the cystic duct take-off, 226 cystic duct patterns were divided into 3 patterns: Type I (193, 85.4%), located on the right and angled up; Type II (7, 3.1%), located on the right and angled down; and Type III (26, 11.5%), located on the left and angled up. Type I was further divided into three subtypes: Line type, S type (S1, not surrounding the common bile duct; S2, surrounding the common bile duct), and α type (α1, forward α; α2, reverse α). Types I and III cystic ducts were easier to be cannulated with a higher success rate (85.1 and 86.4%, respectively) compared with Type II cystic duct (75%) despite no statistically significant difference. The reasons for the failure of gallbladder cannulation included invisible cyst duct take-off, severe cyst duct stenosis, impacted stones in cyst duct or neck of the gallbladder, sharply angled cyst duct, and markedly dilated cyst duct with the tortuous valves of Heister. CONCLUSION: Classification of cystic duct patterns was helpful in guiding endoscopic transpapillary gallbladder cannulation.