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1.
Cell ; 179(5): 1160-1176.e24, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31730855

RESUMO

Pediatric-onset colitis and inflammatory bowel disease (IBD) have significant effects on the growth of infants and children, but the etiopathogenesis underlying disease subtypes remains incompletely understood. Here, we report single-cell clustering, immune phenotyping, and risk gene analysis for children with undifferentiated colitis, Crohn's disease, and ulcerative colitis. We demonstrate disease-specific characteristics, as well as common pathogenesis marked by impaired cyclic AMP (cAMP)-response signaling. Specifically, infiltration of PDE4B- and TNF-expressing macrophages, decreased abundance of CD39-expressing intraepithelial T cells, and platelet aggregation and release of 5-hydroxytryptamine at the colonic mucosae were common in colitis and IBD patients. Targeting these pathways by using the phosphodiesterase inhibitor dipyridamole restored immune homeostasis and improved colitis symptoms in a pilot study. In summary, comprehensive analysis of the colonic mucosae has uncovered common pathogenesis and therapeutic targets for children with colitis and IBD.


Assuntos
Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/terapia , Mucosa Intestinal/patologia , Antígenos CD/metabolismo , Apirase/metabolismo , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Morte Celular/efeitos dos fármacos , Microambiente Celular/efeitos dos fármacos , Criança , Estudos de Coortes , Colo/patologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Dipiridamol/farmacologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Predisposição Genética para Doença , Homeostase/efeitos dos fármacos , Humanos , Imunoglobulina G/sangue , Memória Imunológica , Inflamação/patologia , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/genética , Interferon Tipo I/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Metilprednisolona/farmacologia , Células Mieloides/efeitos dos fármacos , Células Mieloides/metabolismo
2.
Haematologica ; 109(9): 2955-2968, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38385251

RESUMO

Mutations in the master hematopoietic transcription factor GATA1 are often associated with functional defects in erythropoiesis and megakaryopoiesis. In this study, we identified a novel GATA1 germline mutation (c.1162delGG, p.Leu387Leufs*62) in a patient with congenital anemia and occasional thrombocytopenia. The C-terminal GATA1, a rarely studied mutational region, undergoes frameshifting translation as a consequence of this double-base deletion mutation. To investigate the specific function and pathogenic mechanism of this mutant, in vitro mutant models of stable re-expression cells were generated. The mutation was subsequently validated to cause diminished transcriptional activity of GATA1 and defective differentiation of erythroid and megakaryocytes. Using proximity labeling and mass spectrometry, we identified selective alterations in the proximal protein networks of the mutant, revealing decreased binding to a set of normal GATA1-interaction proteins, including the essential co-factor FOG1. Notably, our findings further demonstrated enhanced recruitment of the protein arginine methyltransferase PRMT6, which mediates histone modification at H3R2me2a and represses transcription activity. We also found an enhanced binding of this mutant GATA1/PRMT6 complex to the transcriptional regulatory elements of GATA1's target genes. Moreover, treatment of the PRMT6 inhibitor MS023 could partially rescue the inhibited transcriptional and impaired erythroid differentiation caused by the GATA1 mutation. Taken together, our results provide molecular insights into erythropoiesis in which mutation leads to partial loss of GATA1 function, and the role of PRMT6 and its inhibitor MS023 in congenital anemia, highlighting PRMT6 binding as a negative factor of GATA1 transcriptional activity in aberrant hematopoiesis.


Assuntos
Fator de Transcrição GATA1 , Mutação em Linhagem Germinativa , Ligação Proteica , Proteína-Arginina N-Metiltransferases , Humanos , Fator de Transcrição GATA1/genética , Fator de Transcrição GATA1/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Diferenciação Celular/genética , Eritropoese/genética , Masculino , Feminino , Anemia/genética
3.
Phys Rev Lett ; 133(12): 126602, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39373446

RESUMO

Chiral bulk Landau levels and surface arcs, as the two distinctive features unique to Weyl semimetals, have each attracted enormous interest. Recent works have revealed that surface-arc modes can support one-sided chiral hinge modes, a hallmark of the three-dimensional quantum Hall effect, as a combined result of chiral Landau levels of bulk states and magnetic response of surface arcs. Here, we exploit a two-dimensional phononic crystal to construct an ideal Weyl semimetal under a pseudomagnetic field, in which a structural parameter is combined to construct a synthetic three-dimensional space. By directly measuring the acoustic pressure fields, we have not only visualized the one-sided chiral hinge modes, but also observed the quantized Landau level modes. The results pave the way to explore the high-dimensional quantum Hall physics in low-dimensional phononic platforms.

4.
Phys Rev Lett ; 132(6): 066601, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38394560

RESUMO

Higher-order topological insulators and semimetals, which generalize the conventional bulk-boundary correspondence, have attracted extensive research interest. Among them, higher-order Weyl semimetals feature twofold linear crossing points in three-dimensional momentum space, 2D Fermi-arc surface states, and 1D hinge states. Higher-order nodal-point semimetals possessing Weyl points or Dirac points have been implemented. However, higher-order nodal-line or nodal-surface semimetals remain to be further explored in experiments in spite of many previous theoretical efforts. In this work, we realize a second-order nodal-line semimetal in 3D phononic crystals. The bulk nodal lines, 2D drumhead surface states guaranteed by Zak phases, and 1D flat hinge states attributed to k_{z}-dependent quadrupole moments are observed in simulations and experiments. Our findings of nondispersive surface and hinge states may promote applications in acoustic sensing and energy harvesting.

5.
Phys Rev Lett ; 132(26): 266602, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38996328

RESUMO

Twisted moiré materials, a new class of layered structures with different twist angles for neighboring layers, are attracting great attention because of the rich intriguing physical phenomena associated with them. Of particular interest are the topological network modes, first proposed in the small angle twisted bilayer graphene under interlayer bias. Here we report the observations of such topological network modes in twisted moiré phononic crystals without requiring the external bias fields. Acoustic topological network modes that can be constructed in a wide range of twist angles are both observed in the domain walls with and without reconstructions, which serve as the analogy of the lattice relaxations in electronic moiré materials. Topological robustness of the topological network modes is observed by introducing valley-preserved defects to the network channel. Furthermore, the network can be reconfigured into two-dimensional patterns with any desired connectivity, offering a unique prototype platform for acoustic applications.

6.
J Clin Gastroenterol ; 58(1): 53-56, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36507929

RESUMO

OBJECTIVES: This study aimed to confirm whether premedication with pronase before endoscopy improves mucosal visualization and increases precancerous lesion and cancer lesion detection rates. MATERIALS AND METHODS: From June 2018 to April 2019, out-patients scheduled for endoscopy from 13 hospitals were screened to be randomly allocated in a 2:1 ratio to premedication with pronase (group A) and water (group B). The primary endpoint was mucosal visibility scores, and the secondary endpoint was precancerous and cancer lesion detection rates. This trial was registered at Chinese Clinical Trial Registry, and the registration number was ChiCTR1800016853. RESULTS: Group A showed significantly lower mucosal visibility scores (better mucosal visibility) of esophagus, stomach, and duodenum than group B, with all P -values <0.001. The overall cancer detection rates between group A and group B were 0.83 and 1.08%, and overall detection rates of precancerous and cancer lesion were 4.4 and 4.9%, both without significant difference ( P =1.000 and 0.824). In addition, the flushing volume (milliliter) of group A (10.52±23.41) was less than group B (36.30±52.11) ( P <0.001), and the flushing frequency of group A (0.46±1.01) was fewer than group B (1.62±2.12) ( P <0.001). CONCLUSIONS: Premedication with pronase could achieve better mucosal visibility and decrease flushing frequency and volume, but may not increase lesion detection rates.


Assuntos
Endoscopia Gastrointestinal , Lesões Pré-Cancerosas , Humanos , Pronase/uso terapêutico , Estudos Prospectivos , Pré-Medicação
7.
Nature ; 560(7716): 61-64, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30068954

RESUMO

Reflection and refraction of waves occur at the interface between two different media. These two fundamental interfacial wave phenomena form the basis of fabricating various wave components, such as optical lenses. Classical refraction-now referred to as positive refraction-causes the transmitted wave to appear on the opposite side of the interface normal compared to the incident wave. By contrast, negative refraction results in the transmitted wave emerging on the same side of the interface normal. It has been observed in artificial materials1-5, following its theoretical prediction6, and has stimulated many applications including super-resolution imaging7. In general, reflection is inevitable during the refraction process, but this is often undesirable in designing wave functional devices. Here we report negative refraction of topological surface waves hosted by a Weyl phononic crystal-an acoustic analogue of the recently discovered Weyl semimetals8-12. The interfaces at which this topological negative refraction occurs are one-dimensional edges separating different facets of the crystal. By tailoring the surface terminations of the Weyl phononic crystal, constant-frequency contours of surface acoustic waves can be designed to produce negative refraction at certain interfaces, while positive refraction is realized at different interfaces within the same sample. In contrast to the more familiar behaviour of waves at interfaces, unwanted reflection can be prevented in our crystal, owing to the open nature of the constant-frequency contours, which is a hallmark of the topologically protected  surface states in Weyl crystals8-12.

8.
Int J Med Sci ; 21(1): 61-69, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38164345

RESUMO

Background: Primary biliary cholangitis (PBC) is a rare autoimmune liver disease with few effective treatments and a poor prognosis, and its incidence is on the rise. There is an urgent need for more targeted treatment strategies to accurately identify high-risk patients. The use of stochastic survival forest models in machine learning is an innovative approach to constructing a prognostic model for PBC that can improve the prognosis by identifying high-risk patients for targeted treatment. Method: Based on the inclusion and exclusion criteria, the clinical data and follow-up data of patients diagnosed with PBC-associated cirrhosis between January 2011 and December 2021 at Taizhou Hospital of Zhejiang Province were retrospectively collected and analyzed. Data analyses and random survival forest model construction were based on the R language. Result: Through a Cox univariate regression analysis of 90 included samples and 46 variables, 17 variables with p-values <0.1 were selected for initial model construction. The out-of-bag (OOB) performance error was 0.2094, and K-fold cross-validation yielded an internal validation C-index of 0.8182. Through model selection, cholinesterase, bile acid, the white blood cell count, total bilirubin, and albumin were chosen for the final predictive model, with a final OOB performance error of 0.2002 and C-index of 0.7805. Using the final model, patients were stratified into high- and low-risk groups, which showed significant differences with a P value <0.0001. The area under the curve was used to evaluate the predictive ability for patients in the first, third, and fifth years, with respective results of 0.9595, 0.8898, and 0.9088. Conclusion: The present study constructed a prognostic model for PBC-associated cirrhosis patients using a random survival forest model, which accurately stratified patients into low- and high-risk groups. Treatment strategies can thus be more targeted, leading to improved outcomes for high-risk patients.


Assuntos
Cirrose Hepática Biliar , Humanos , Prognóstico , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/tratamento farmacológico , Ácido Ursodesoxicólico/uso terapêutico , Estudos Retrospectivos , Cirrose Hepática/tratamento farmacológico
9.
Cell Mol Life Sci ; 80(2): 41, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36633714

RESUMO

SRC is the first identified oncogene, and its aberrant activation has been implicated as a driving event in tumor initiation and progression. However, its role in cancer stemness regulation and the underlying regulatory mechanism are still elusive. Here, we identified a YAP1 tyrosine phosphorylation-dependent YAP1-KLF5 oncogenic module, as the key downstream mediator of SRC kinase regulating cancer stemness and metastasis in triple-negative breast cancer (TNBC). SRC was overexpressed in TNBC patient tissues and its expression level was highly correlated with the tumor malignancy. SRC activation induced, while inhibition of SRC kinase reduced the cancer stemness, tumor cell growth and metastasis in vitro and in vivo. Transcriptomic and proteomic analysis revealed that SRC-mediated YAP1 tyrosine phosphorylation induced its interaction with Kruppel-like factor 5 (KLF5) to form a YAP1/TEAD-KLF5 complex in TNBC cells. YAP1-KLF5 association further promoted TEAD-mediated transcriptional program independently of canonical Hippo kinases, which eventually gave rise to the enhanced cancer stemness and metastasis. Disruption of YAP1-KLF5 module in TNBC cells dramatically attenuated the SRC-induced cancer stemness and metastasis in vitro and in vivo. Accordingly, co-upregulations of SRC and YAP1-KLF5 module in TNBC tissues were significantly positively correlated with the tumor malignance. Altogether, our work presents a novel tyrosine phosphorylation-dependent YAP1-KLF5 oncogenic module governing SRC-induced cancer stemness and metastasis in TNBC. Therefore, targeting YAP1/KLF5-mediated transcription may provide a promising strategy for TNBC treatment with SRC aberrantly activation.


Assuntos
Proteínas Tirosina Quinases , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/metabolismo , Proteômica , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Quinases da Família src/metabolismo , Proliferação de Células , Tirosina , Linhagem Celular Tumoral , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo
10.
Sensors (Basel) ; 24(16)2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39205132

RESUMO

The surge in image data has significantly increased the pressure on storage and transmission, posing new challenges for image compression technology. The structural texture of an image implies its statistical characteristics, which is effective for image encoding and decoding. Consequently, content-adaptive compression methods based on learning can better capture the content attributes of images, thereby enhancing encoding performance. However, learned image compression methods do not comprehensively account for both the global and local correlations among the pixels within an image. Moreover, they are constrained by rate-distortion optimization, which prevents the attainment of a compact representation of image attributes. To address these issues, we propose a syntax-guided content-adaptive transform framework that efficiently captures image attributes and enhances encoding efficiency. Firstly, we propose a syntax-refined side information module that fully leverages syntax and side information to guide the adaptive transformation of image attributes. Moreover, to more thoroughly exploit the global and local correlations in image space, we designed global-local modules, local-global modules, and upsampling/downsampling modules in codecs, further eliminating local and global redundancies. The experimental findings indicate that our proposed syntax-guided content-adaptive image compression model successfully adapts to the diverse complexities of different images, which enhances the efficiency of image compression. Concurrently, the method proposed has demonstrated outstanding performance across three benchmark datasets.

11.
Phys Rev Lett ; 130(11): 116103, 2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-37001063

RESUMO

Higher-order topological phases have raised widespread interest in recent years with the occurrence of the topological boundary states of dimension two or more less than that of the system bulk. The higher-order topological states have been verified in gapped phases, in a wide variety of systems, such as photonic and acoustic systems, and recently also observed in gapless semimetal phase, such as Weyl and Dirac phases, in systems alike. The higher-order topology is signaled by the hinge states emerging in the common band gaps of the bulk states and the surface states. In this Letter, we report our first prediction and observation of a new type of hinge states, the bound hinge states in the continuum (BHICs) bulk band, in a higher-order Weyl semimetal implemented in phononic crystal. In contrast to the hinge state in gap, which is characterized by the bulk polarization, the BHIC is identified by the nontrivial surface polarization. The finding of the topological BHICs broadens our insight to the topological states, and may stimulate similar researches in other systems such as electronic, photonic, and cold atoms systems. Our Letter may pave the way toward high-Q acoustic devices in application.

12.
Chemistry ; 29(32): e202203693, 2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-36918515

RESUMO

New molecular scaffolds of C-, Z- and box-shaped configurations are constructed by fusing phenazine and pyrene units with oxanorbornene. As revealed by X-ray crystallography, the C-shaped molecules exhibit two interesting π-π stacking modes of phenazine depending on the substituting groups, and the box-shaped molecule accommodates two chloroform molecules in the cavity and forms H-bonds with another four molecules of chloroform. The C- and Z-shaped molecules as a pair of diastereomers exhibit almost the same charge transfer absorption and emission including positive solvatochromism, indicating that the intramolecular charge transfer between pyrene (π-donor) and phenazine (π-acceptor) is not dependent on the overall molecular geometry.


Assuntos
Clorofórmio , Pirenos , Modelos Moleculares , Fenazinas
13.
Prev Med ; 174: 107605, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37419420

RESUMO

Gastric cancer continues to be a significant health concern in China, with a high incidence rate. To mitigate its impact, early detection and treatment is key. However, conducting large-scale endoscopic gastric cancer screening is not feasible in China. Instead, a more appropriate approach would be to initially screen high-risk groups and follow up with endoscopic testing as needed. We conducted a study on 25,622 asymptomatic participants aged 45-70 years from a free gastric cancer screening program in the Taizhou city government's Minimum Living Guarantee Crowd (MLGC) initiative. Participants completed questionnaires, blood tests, and underwent gastrin-17 (G-17), pepsinogen I and II (PGI and PGII), and H. pylori IgG antibody (IgG) assessments. Using the light gradient boosting machine (lightGBM) algorithm, we developed a predictive model for gastric cancer risk. In the full model, F1 score was 2.66%, precision was 1.36%, and recall was 58.14%. In the high-risk model, F1 score was 2.51%, precision was 1.27%, and recall was 94.55%. Excluding IgG, the F1 score was 2.73%, precision was 1.40%, and recall was 68.62%. We conclude that H. pylori IgG appears to be able to be excluded from the prediction model without significantly affecting its performance, which is important from a health economic point of view. It suggests that screening indicators can be optimized, and expenditures reduced. These findings can have important implications for policymakers, as we can focus resources on other important aspects of gastric cancer prevention and control.


Assuntos
Helicobacter pylori , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/prevenção & controle , Pepsinogênio A , Detecção Precoce de Câncer , Pepsinogênio C , Imunoglobulina G
14.
Breast Cancer Res ; 24(1): 99, 2022 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-36581908

RESUMO

Breast cancer (BC) has been ranked the most common malignant tumor throughout the world and is also a leading cause of cancer-related deaths among women. SRC family kinases (SFKs) belong to the non-receptor tyrosine kinase (nRTK) family, which has eleven members sharing similar structure and function. Among them, SRC is the first identified proto-oncogene in mammalian cells. Oncogenic overexpression or activation of SRC has been revealed to play essential roles in multiple events of BC progression, including tumor initiation, growth, metastasis, drug resistance and stemness regulations. In this review, we will first give an overview of SRC kinase and SRC-relevant functions in various subtypes of BC and then systematically summarize SRC-mediated signaling transductions, with particular emphasis on SRC-mediated substrate phosphorylation in BC. Furthermore, we will discuss the progress of SRC-based targeted therapies in BC and the potential future direction.


Assuntos
Neoplasias da Mama , Quinases da Família src , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Fosforilação , Transdução de Sinais , Quinases da Família src/genética , Quinases da Família src/metabolismo
15.
Biochem Biophys Res Commun ; 615: 163-171, 2022 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-35665610

RESUMO

BACKGROUNDS: Although several studies on mutant p53 reported cancer-promoting activities via "gain-of-function", the mechanism underlying these differences in function between p53 R175H, R175P, and p53 wild-type (WT) remains unclear. METHODS: Linking miniTurbo with p53 WT, R175H, and R175P, the expression of fusion and biotinylated proteins were assessed by Western blotting. The function and subcellular localization of fusion proteins were detected by apoptosis assay and immunofluorescence, respectively. Biotinylated proteins were analyzed by liquid chromatography-tandem mass spectrometry, followed by bioinformatics analysis. Small-scale pull-downs and Co-Immunoprecipitation were performed to validate the interaction between mutant or p53 WT and biotinylated proteins. RESULTS: The fusion protein's cellular localization and function were consistent with those of previous studies on the corresponding p53. Comparative profiles of R175H versus WT showed that most of the interacting proteins belonged to the intracellular organelle lumen, and the pathways involved were metabolism and genetic information processing. Comparative profiles of R175P versus WT suggested that the majority of the interacting proteins belonged to the intracellular organelle lumen and the extracellular membrane-bounded organelle, and the pathways involved were metabolism and genetic information processing pathways. The comparison between R175H and R175P revealed that most interacting proteins belonged to the organelle lumen, and pathways involved were genetic information processing pathways. Finally, the mutation of p53 significantly altered the interaction with the target proteins were confirmed. CONCLUSION: We verified the reliability of the miniTurbo system and obtained candidate targets of mutant p53, which provided new thoughts on the mechanism of mutant p53 gain-of-function and new potential targets for cancer therapy.


Assuntos
Proteína Supressora de Tumor p53 , Linhagem Celular Tumoral , Proteínas Mutantes/metabolismo , Mutação , Reprodutibilidade dos Testes , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
16.
Gastrointest Endosc ; 95(2): 269-280.e6, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34547254

RESUMO

BACKGROUND AND AIMS: White-light endoscopy (WLE) is the most pivotal tool to detect gastric cancer in an early stage. However, the skill among endoscopists varies greatly. Here, we aim to develop a deep learning-based system named ENDOANGEL-LD (lesion detection) to assist in detecting all focal gastric lesions and predicting neoplasms by WLE. METHODS: Endoscopic images were retrospectively obtained from Renmin Hospital of Wuhan University (RHWU) for the development, validation, and internal test of the system. Additional external tests were conducted in 5 other hospitals to evaluate the robustness. Stored videos from RHWU were used for assessing and comparing the performance of ENDOANGEL-LD with that of experts. Prospective consecutive patients undergoing upper endoscopy were enrolled from May 6, 2021 to August 2, 2021 in RHWU to assess clinical practice applicability. RESULTS: Over 10,000 patients undergoing upper endoscopy were enrolled in this study. The sensitivities were 96.9% and 95.6% for detecting gastric lesions and 92.9% and 91.7% for diagnosing neoplasms in internal and external patients, respectively. In 100 videos, ENDOANGEL-LD achieved superior sensitivity and negative predictive value for detecting gastric neoplasms from that of experts (100% vs 85.5% ± 3.4% [P = .003] and 100% vs 86.4% ± 2.8% [P = .002], respectively). In 2010 prospective consecutive patients, ENDOANGEL-LD achieved a sensitivity of 92.8% for detecting gastric lesions with 3.04 ± 3.04 false positives per gastroscopy and a sensitivity of 91.8% and specificity of 92.4% for diagnosing neoplasms. CONCLUSIONS: Our results show that ENDOANGEL-LD has great potential for assisting endoscopists in screening gastric lesions and suspicious neoplasms in clinical work. (Clinical trial registration number: ChiCTR2100045963.).


Assuntos
Inteligência Artificial , Neoplasias Gástricas , Gastroscopia/métodos , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia
17.
Endoscopy ; 54(8): 771-777, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35272381

RESUMO

BACKGROUND AND STUDY AIMS: Endoscopic reports are essential for the diagnosis and follow-up of gastrointestinal diseases. This study aimed to construct an intelligent system for automatic photo documentation during esophagogastroduodenoscopy (EGD) and test its utility in clinical practice. PATIENTS AND METHODS: Seven convolutional neural networks trained and tested using 210,198 images were integrated to construct the endoscopic automatic image reporting system (EAIRS). We tested its performance through man-machine comparison at three levels: internal, external, and prospective test. Between May 2021 and June 2021, patients undergoing EGD at Renmin Hospital of Wuhan University were recruited. The primary outcomes were accuracy for capturing anatomical landmarks, completeness for capturing anatomical landmarks, and detected lesions. RESULTS: The EAIRS outperformed endoscopists in retrospective internal and external test. A total of 161 consecutive patients were enrolled in the prospective test. The EAIRS achieved an accuracy of 95.2% in capturing anatomical landmarks in the prospective test. It also achieved higher completeness on capturing anatomical landmarks compared with endoscopists: (93.1% vs. 88.8%), and was comparable to endoscopists on capturing detected lesions: (99.0% vs. 98.0%). CONCLUSIONS: The EAIRS can generate qualified image reports and could be a powerful tool for generating endoscopic reports in clinical practice.


Assuntos
Aprendizado Profundo , Endoscopia do Sistema Digestório , Endoscopia/métodos , Endoscopia do Sistema Digestório/métodos , Humanos , Estudos Prospectivos
18.
J Bone Miner Metab ; 40(1): 40-55, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34626248

RESUMO

INTRODUCTION: Heterotopic ossification of tendons and ligaments is a painful and debilitating disease with no effective treatment. Although aging has been reported to be correlated with the occurrence and development of this disease, the mechanism remains unknown. MATERIALS AND METHODS: In the present study, we generated Bmal1-/- mice, which disrupted the circadian clock and displayed premature aging, as an aging model to explore the role of Bmal1 in TGF-beta (ß)/BMP signaling in progressive heterotopic ossification of tendons and ligaments with aging. RESULTS: We first confirmed that BMAL1 expression is downregulated in human fibroblasts from ossification of the posterior longitudinal ligament using online datasets. Bmal1 deficiency in mice caused significantly progressive heterotopic ossification with aging starting at week 6, notably in the Achilles tendons and posterior longitudinal ligaments. Ossification of the Achilles tendons was accompanied by progressive motor dysfunction of the ankle joint. Histology and immunostaining showed markedly increased endochondral ossification in the posterior longitudinal ligaments and Achilles tendons of Bmal1-/- mice. Ligament-derived Bmal1-/- fibroblasts showed an osteoblast-like phenotype, upregulated osteogenic and chondrogenic markers, and activated TGFß/BMP signaling, which was enhanced by TGFß1 stimulation. Furthermore, Bmal1-/- mouse embryonic fibroblasts had a stronger potential for osteogenic differentiation with activation of TGFß/BMP signaling. CONCLUSIONS: These findings demonstrated that Bmal1 negatively regulates endochondral ossification in heterotopic ossification of tendons and ligaments with aging via TGFß/BMP signaling, thereby identifying a new regulatory mechanism in age-related heterotopic ossification of tendons and ligaments.


Assuntos
Tendão do Calcâneo , Ossificação Heterotópica , Fatores de Transcrição ARNTL/genética , Envelhecimento , Animais , Fibroblastos , Camundongos , Ossificação Heterotópica/genética , Osteogênese , Fator de Crescimento Transformador beta
19.
Surg Endosc ; 36(5): 3619-3628, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35059840

RESUMO

BACKGROUND AND AIMS: Currently, published data of endoscopic resection (ER) for giant (≥ 6 cm) gastric subepithelial tumors originating from the muscularis propria layer (MP-SETs) are extremely rare and limited to only case reports. The aim of this study was thus to assess the feasibility of using ER for giant (≥ 6 cm) gastric MP-SETs in a case series. METHODS: Between July 2013 and December 2020, a total of 23 patients with giant (≥ 6 cm) gastric MP-SETs were treated with ER in the endoscopic center of Taizhou hospital. The study assessed outcomes of en bloc resection, complete resection, total complications, and local residual/recurrence of tumors. RESULTS: The mean procedure time was 112.2 min. En bloc resection was achieved in 22 tumors (95.7%). En bloc removal from the stomach and complete resection were achieved in 6 patients (26.1%). The rate of complete resection differed significantly depending on the minimum tumor diameter (P < 0.001). During hospitalization, 4 patients had complications, including localized peritonitis (3/23, 13.0%) and pulmonary infection (1/23, 4.3%). These 4 patients recovered successfully after conservative medical treatment. Histopathological examination revealed that 18 tumors were gastrointestinal stromal tumors (GISTs), and 5 tumors were leiomyoma. No patients were observed to have residual or recurrent tumors during the follow-up. CONCLUSIONS: Although ER for giant (≥ 6 cm) gastric MP-SETs was associated with several technical challenges and a relatively low complete resection rate, this technique was found to be a feasible therapeutic method for selected patients with a giant (≥ 6 cm) gastric MP-SETs when performed by an experienced endoscopic team.


Assuntos
Ressecção Endoscópica de Mucosa , Tumores do Estroma Gastrointestinal , Laparoscopia , Neoplasias Gástricas , Ressecção Endoscópica de Mucosa/métodos , Estudos de Viabilidade , Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/cirurgia , Gastroscopia/métodos , Humanos , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
20.
Surg Endosc ; 36(4): 2705-2711, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35075524

RESUMO

BACKGROUND: With the increasing realization of the importance of gallbladder function, choledochoscopic gallbladder-preserving surgery has been advocated for benign gallbladder diseases. However, limited information is available regarding the use of endoscopic gallbladder-preserving surgery (EGPS) for patients with benign gallbladder diseases. The aim of this study was to evaluate the feasibility of EGPS for benign gallbladder diseases. METHODS: Between June 2020 and January 2021, 22 patients with gallbladder stones and/or gallbladder polyps were treated with EGPS. The main outcome measures included the rate of complications, residual gallbladder stones, and gallbladder stone recurrence. RESULTS: In this study, transgastric EGPS was successfully performed in 22 patients (13 female, 9 male) with benign gallbladder diseases, and included 8 cases of multiple gallstones, 4 cases of gallbladder polyps with gallstones, 6 cases of multiple gallbladder polyps, 2 cases of single gallstone, and 2 case of singe gallbladder polyp. The median time of transgastric EGPS was 118 min. During hospitalization, 4 patients suffered localized peritonitis (4/22, 18.2%), and these patients successfully recovered after conservative medical treatment. None of the patients experienced massive bleeding, delayed bleeding, diffuse peritonitis, or any other serious complications. During the median follow-up of 4 months, 1 patient suffered residual gallstone, while no gallstone recurrence or deaths related to transgastric EGPS occurred in any patients. CONCLUSIONS: Transgastric EGPS appears to be a feasible treatment method in selected patients with benign gallbladder diseases. However, as it is a new technique, further studies are needed to explore the long-term effectiveness of transgastric EGPS.


Assuntos
Doenças da Vesícula Biliar , Cálculos Biliares , Peritonite , Pólipos , Estudos de Viabilidade , Feminino , Vesícula Biliar/cirurgia , Doenças da Vesícula Biliar/diagnóstico por imagem , Doenças da Vesícula Biliar/patologia , Doenças da Vesícula Biliar/cirurgia , Cálculos Biliares/diagnóstico por imagem , Cálculos Biliares/cirurgia , Humanos , Masculino , Pólipos/patologia , Pólipos/cirurgia
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