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1.
World J Clin Cases ; 12(4): 865-871, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38322683

RESUMO

BACKGROUND: Meckel's diverticulum is a common congenital malformation of the small intestine, with the three most common complications being obstruction, perforation, and inflammation. To date, only a few cases have been reported worldwide. In children, the clinical symptoms are similar to appendicitis. As most of the imaging features are nonspecific, the preoperative diagnosis is not precise. In addition, the clinical characteristics are highly similar to pediatric acute appendicitis, thus special attention is necessary to distinguish Meckel's diverticulum from pediatric appendicitis. Patients with poor disease control should undergo laparoscopic exploration to avoid serious complications, including intestinal necrosis, intestinal perforation and gastrointestinal bleeding. CASE SUMMARY: This report presents three cases of appendicitis in children combined with intestinal obstruction, which was caused by fibrous bands (ligaments) arising from the top part of Meckel's diverticulum, diverticular perforation, and diverticular inflammation. All three patients, aged 11-12 years, had acute appendicitis as their initial clinical presentation. All were treated by laparoscopic surgery with a favorable outcome. A complete dataset including clinical presentation, diagnostic imaging, surgical information, and histopathologic findings was also provided. CONCLUSION: Preoperative diagnosis of Meckel's diverticulum and its complications is challenging because its clinical signs and complications are similar to those of appendicitis in children. Laparoscopy combined with laparotomy is useful for diagnosis and treatment.

2.
J Phys Chem A ; 128(6): 1041-1048, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38311924

RESUMO

To determine the H-abstraction reaction probabilities of H/O/OH radicals with a polypropylene (PP) surface, a first-principles calculation was performed based on the DLPNO-CCSD(T)/CBS//M06-2X-D3/def-TZVP theory level. The PP chain model used in this study was 2,4,6-trimethylheptane. The rate constants of the H/O/OH radicals with the isolated PP chain model were calculated based on the conventional transition-state theory. By comparing the experimental values and considering the error factors and their compensation, it was concluded that the orders of magnitude of the predicted rate constants were accurate. The resulting rate constants were converted to reaction probabilities between the H/O/OH radicals and the PP surface. The method used in this study is applicable for obtaining theoretical values of surface reaction probabilities based on first-principles calculations. The calculation at the DLPNO-CCSD(T)/CBS theory level has high accuracy but consumes a large amount of computational resources. The study also demonstrated that the double-hybrid functionals, wB97x-2-D3(BJ) and rev-DSD-PBEP86-D3(BJ), with a 3-ζ or 4-ζ basis set, could reproduce the electronic energy values obtained from DLPNO-CCSD(T)/CBS while using only approximately 1/100 of the computational resources required by the latter under our computer configuration.

3.
Cureus ; 16(1): e52688, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38384624

RESUMO

Primary bladder lymphoma, a rare form of non-Hodgkin's lymphoma, is diagnosed through histopathology and immunostaining. Most bladder lymphomas are of the B-cell type, with a higher incidence in women and often presenting with hematuria. This report details an exceptionally rare case of primary bladder T-cell lymphoma. A 50-year-old male, without hematuria or other symptoms, was diagnosed during a routine ultrasound. A computed tomography scan showed a tumor located in the anterior, right, and posterior walls. The patient underwent transurethral resection of the bladder lesion. Pathological examination of the tumor showed that it was composed of lymphoid tissue, in accordance with peripheral T-cell lymphoma of non-Hodgkin subtype.

4.
Cancer Res ; 84(3): 372-387, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37963207

RESUMO

Neuronal activity can drive progression of high-grade glioma by mediating mitogen production and neuron-glioma synaptic communications. Glioma stem cells (GSC) also play a significant role in progression, therapy resistance, and recurrence in glioma, which implicates potential cross-talk between neuronal activity and GSC biology. Here, we manipulated neuronal activity using chemogenetics in vitro and in vivo to study how it influences GSCs. Neuronal activity supported glioblastoma (GBM) progression and radioresistance through exosome-induced proneural-to-mesenchymal transition (PMT) of GSCs. Molecularly, neuronal activation led to elevated miR-184-3p in neuron-derived exosomes that were taken up by GSCs and reduced the mRNA N6-methyladenosine (m6A) levels by inhibiting RBM15 expression. RBM15 deficiency decreased m6A modification of DLG3 mRNA and subsequently induced GSC PMT by activating the STAT3 pathway. Loss of miR-184-3p in cortical neurons reduced GSC xenograft growth, even when neurons were activated. Levetiracetam, an antiepileptic drug, reduced the neuronal production of miR-184-3p-enriched exosomes, inhibited GSC PMT, and increased radiosensitivity of tumors to prolong survival in xenograft mouse models. Together, these findings indicate that exosomes derived from active neurons promote GBM progression and radioresistance by inducing PMT of GSCs. SIGNIFICANCE: Active neurons secrete exosomes enriched with miR-184-3p that promote glioblastoma progression and radioresistance by driving the proneural-to-mesenchymal transition in glioma stem cells, which can be reversed by antiseizure medication levetiracetam.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , MicroRNAs , Humanos , Animais , Camundongos , Glioblastoma/patologia , Neoplasias Encefálicas/patologia , Levetiracetam/metabolismo , Levetiracetam/uso terapêutico , Células-Tronco Neoplásicas/patologia , Glioma/patologia , Neurônios/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética
5.
CNS Neurosci Ther ; 30(1): e14408, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37564004

RESUMO

AIMS: Adenosine 2A receptor (A2A R) is widely expressed in the brain and plays important roles in neuroinflammation, and the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome is a crucial component of the innate immune system while the regulation of A2A R on it in the central nervous system (CNS) has not been clarified. METHODS: The effects of microglial A2A R on NLRP3 inflammasome assembly and activation were investigated in wild-type, A2A R- or NLRP3-knockout primary microglia with pharmacological treatment. Microglial A2A R or NLRP3 conditional knockout mice were used to interrogate the effects of this regulation on neuroinflammation posttraumatic brain injury (TBI). RESULTS: We found that A2A R directly interacted with NLRP3 and facilitated NLRP3 inflammasome assembly and activation in primary microglia while having no effects on mRNA levels of inflammasome components. Inhibition of the interaction via A2A R agonist or knockout attenuated inflammasome assembly and activation in vitro. In the TBI model, microglial A2A R and NLRP3 were co-expressed at high levels in microglia next to the peri-injured cortex, and abrogating of this interaction by microglial NLRP3 or A2A R conditional knockout attenuated the neurological deficits and neuropathology post-TBI via reducing the NLRP3 inflammasome activation. CONCLUSION: Our results demonstrated that inhibition of the interaction between A2A R and NLRP3 in microglia could mitigate the NLRP3 inflammasome assembly and activation and ameliorate the neuroinflammation post-TBI. It provides new insights into the effects of A2A R on neuroinflammation regulation post-TBI and offers a potential target for the treatment of NLRP3 inflammasome-related CNS diseases.


Assuntos
Lesões Encefálicas Traumáticas , Inflamassomos , Animais , Camundongos , Adenosina/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Inflamassomos/metabolismo , Camundongos Knockout , Microglia , Doenças Neuroinflamatórias , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
6.
Clin Cancer Res ; 30(6): 1160-1174, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-37855702

RESUMO

PURPOSE: Neuronal activity in the brain has been reported to promote the malignant progression of glioma cells via nonsynaptic paracrine and electrical synaptic integration mechanisms. However, the interaction between neuronal activity and the immune microenvironment in glioblastoma (GBM) remains largely unclear. EXPERIMENTAL DESIGN: By applying chemogenetic techniques, we enhanced and inhibited neuronal activity in vitro and in a mouse model to study how neuronal activity regulates microglial polarization and affects GBM progression. RESULTS: We demonstrate that hypoxia drove glioma stem cells (GSC) to produce higher levels of glutamate, which activated local neurons. Neuronal activity promoted GBM progression by facilitating microglial M2 polarization through enriching miR-200c-3p in neuron-derived exosomes, which decreased the expression of the m6A writer zinc finger CCCH-type containing 13 (ZC3H13) in microglia, impairing methylation of dual specificity phosphatase 9 (DUSP9) mRNA. Downregulation of DUSP9 promoted ERK pathway activation, which subsequently induced microglial M2 polarization. In the mouse model, cortical neuronal activation promoted microglial M2 polarization whereas cortical neuronal inhibition decreased microglial M2 polarization in GBM xenografts. miR-200c-3p knockdown in cortical neurons impaired microglial M2 polarization and GBM xenograft growth, even when cortical neurons were activated. Treatment with the anti-seizure medication levetiracetam impaired neuronal activation and subsequently reduced neuron-mediated microglial M2 polarization. CONCLUSIONS: These findings indicated that hypoxic GSC-induced neuron activation promotes GBM progression by polarizing microglia via the exosomal miR-200c-3p/ZC3H13/DUSP9/p-ERK pathway. Levetiracetam, an antiepileptic drug, blocks the abnormal activation of neurons in GBM and impairs activity-dependent GBM progression. See related commentary by Cui et al., p. 1073.


Assuntos
Adenina/análogos & derivados , Glioblastoma , Glioma , MicroRNAs , Camundongos , Animais , Humanos , Microglia , MicroRNAs/genética , MicroRNAs/metabolismo , Levetiracetam/metabolismo , Glioma/patologia , Glioblastoma/patologia , Hipóxia/metabolismo , Neurônios , Desmetilação , Microambiente Tumoral/genética
8.
Animals (Basel) ; 13(23)2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38067041

RESUMO

Brachymystax tsinlingensis Li is an endangered cold-water salmonid fish native to China. This study aimed to identify sex-related genes and biological pathways via gonadal transcriptome sequencing of B. tsinlingensis Li. A total of 167,904 unigenes were identified with an average length of 836 bp and an N50 of 1452 bp, of which 84,977 (50.61%) unigenes were successfully annotated in six major databases. Comparative transcriptome analysis identified 22,864 differentially expressed genes (DEGs), of which 17,231 were up-regulated (male-biased genes, mDEGs) and 5633 were down-regulated (female-biased genes, fDEGs). Several DEGs associated with gonadal development were found through Gene Ontology enrichment analysis, such as ccnb1, zp3, bmp15, dmrt1, and psmc3ip. Signaling pathways related to gonadal development were found to be enriched through analysis using the Kyoto Encyclopedia of Genes and Genomes Pathway database, such as genes involves in base excision repair, the notch signaling pathway, neuroactive ligand-receptor interaction, the VEGF signaling pathway, and the estrogen signaling pathway. In addition, mRNA expression levels of 19 DEGs were determined to validate the reliability of the transcriptomic data by quantitative real-time polymerase chain reaction. These results revealed genes and signaling pathways potentially involved in gonadal development in B. tsinlingensis Li and provided basic molecular data for future research on reproductive regulation and breeding of B. tsinlingensis Li.

9.
Oncol Lett ; 26(5): 478, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37818134

RESUMO

Most patients with pancreatic cancer are already in the late stages of the disease when they are diagnosed, and pancreatic cancer is a deadly disease with a poor prognosis. With the advancement of research, immunotherapy has become a new focus in the treatment of tumors. To the best of our knowledge, there is currently no reliable diagnostic or prognostic marker for pancreatic cancer; therefore, the present study investigated the potential of eukaryotic translation initiation factor 2α kinase 2 (EIF2AK2) as a predictive and diagnostic marker for pancreatic cancer. Immunohistochemical staining of clinical samples independently verified that EIF2AK2 expression was significantly higher in clinically operated pancreatic cancer tissues than in adjacent pancreatic tissues., and EIF2AK2 expression and differentially expressed genes (DEGs) were identified using downloadable RNA sequencing data from The Cancer Genome Atlas and Genomic Tumor Expression Atlas. In addition, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analyses and immune cell infiltration were used for functional enrichment analysis of EIF2AK2-associated DEGs. The clinical importance of EIF2AK2 was also determined using Kaplan-Meier survival, Cox regression and time-dependent survival receiver operating characteristic curve analyses, and a predictive nomogram model was generated. Finally, the functional role of EIF2AK2 was assessed in PANC-1 cells using a short hairpin RNA-EIF2AK2 knockdown approach, including CCK-8, wound healing assay, cell cycle and apoptosis assays. The findings suggested that EIF2AK2 may have potential as a diagnostic and prognostic biomarker for patients with pancreatic cancer. Furthermore, EIF2AK2 may provide a new therapeutic target for patients with pancreatic cancer.

10.
Chemosphere ; 341: 140053, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37690558

RESUMO

The catalytic efficiency of photocatalysts highly depends on electron transport and mass transfer. Herein, we designed and prepared an effective H2WO4/Ti3C2/g-C3N4 (HTC) Z-scheme heterojunction through interfacial engineering strategy. The results manifested that 97.4% of Cr(VI) (80 µM, 50 mL) could be removed by HTC heterojunction within 10 min under visible light irradiation. The reduction rate constant of Cr(VI) for H2WO4/g-C3N4 (HC) heterojunction increased by a factor of 21 after introducing the conductive Ti3C2. Moreover, 96% of tetracycline (TC, 10 mg L-1, 50 mL) could be degraded by HTC heterojunction within 30 min. The electronic conductivity and ionic diffusion coefficient of HC heterojunction increased by a factor of 64 and 1064 after adding Ti3C2, respectively. This result indicated that the introduction of highly conductive Ti3C2 significantly improved the electron and mass transfer of the heterojunction. Meanwhile, the HCT heterojunction displayed favorable photocurrent, and keep excellent photostability during the long-term test. Moreover, density functional theory (DFT) calculations demonstrated that the internal electric field (IEF) from g-C3N4 to H2WO4 in HCT heterojunction promotes the combination of the photoinduced electrons in the H2WO4 conduction band (CB) with photoinduced holes in the g-C3N4 valence band (VB), thus accelerating the charge transfer in the HCT Z-scheme heterojunction. The antibacterial efficiency of HTC heterojunction against E. coli and S. aureus could reach up to 98.4% and 99.7%, respectively. The degradation intermediates and the potential degradation mechanism of TC were analyzed and proposed based on the results of HPLC-MS analysis. Moreover, the toxicity of TC and degradation intermediates were estimated by Toxicity Estimation Software (T.E.S.T.) based on quantitative structure-activity relationship (QSAR). This work provided a valuable guideline for designing the effective MXene-based Z-scheme heterojunction for environmental remediation.


Assuntos
Elétrons , Recuperação e Remediação Ambiental , Escherichia coli , Staphylococcus aureus , Titânio , Antibacterianos
11.
J Nanobiotechnology ; 21(1): 233, 2023 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-37481646

RESUMO

BACKGROUND: The immunosuppressive microenvironment in glioma induces immunotherapy resistance and is associated with poor prognosis. Glioma-associated mesenchymal stem cells (GA-MSCs) play an important role in the formation of the immunosuppressive microenvironment, but the mechanism is still not clear. RESULTS: We found that GA-MSCs promoted the expression of CD73, an ectonucleotidase that drives immunosuppressive microenvironment maintenance by generating adenosine, on myeloid-derived suppressor cells (MDSCs) through immunosuppressive exosomal miR-21 signaling. This process was similar to the immunosuppressive signaling mediated by glioma exosomal miR-21 but more intense. Further study showed that the miR-21/SP1/DNMT1 positive feedback loop in MSCs triggered by glioma exosomal CD44 upregulated MSC exosomal miR-21 expression, amplifying the glioma exosomal immunosuppressive signal. Modified dendritic cell-derived exosomes (Dex) carrying miR-21 inhibitors could target GA-MSCs and reduce CD73 expression on MDSCs, synergizing with anti-PD-1 monoclonal antibody (mAb). CONCLUSIONS: Overall, this work reveals the critical role of MSCs in the glioma microenvironment as signal multipliers to enhance immunosuppressive signaling of glioma exosomes, and disrupting the positive feedback loop in MSCs with modified Dex could improve PD-1 blockade therapy.


Assuntos
Glioma , MicroRNAs , Células Supressoras Mieloides , Humanos , Retroalimentação , Imunossupressores , MicroRNAs/genética , Microambiente Tumoral , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/metabolismo , Exossomos/genética , Exossomos/metabolismo , Fator de Transcrição Sp1
12.
Front Aging Neurosci ; 15: 1190869, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37358957

RESUMO

Insulin-like growth factor-1 (IGF-1) is an active polypeptide protein that closely resembles the structural sequence of insulin and is involved in a variety of metabolic processes in the body. Decreased IGF-1 circulation levels are associated with an increased risk of stroke and a poorer prognosis, but the relationship with cerebral small vessel disease (cSVD) is unclear. Some studies found that the level of IGF-1 in patients with cSVD was significantly reduced, but the clinical significance and underlying mechanisms are unknown. This article reviews the correlation between IGF-1 and cerebrovascular disease and explores the potential relationship and mechanism between IGF-1 and cSVD.

13.
Br J Pharmacol ; 180(17): 2250-2265, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37076137

RESUMO

BACKGROUND AND PURPOSE: Renal fibrosis is a common feature of chronic kidney disease. Myeloid fibroblasts and macrophages contribute significantly to the pathogenesis of renal fibrosis. However, the molecular mechanisms underlying myeloid fibroblast activation and macrophage polarization are not fully understood. In this study, we examined the role of Jumonji domain-containing protein-3 (JMJD3) in myeloid fibroblast activation, macrophage polarization, and renal fibrosis development in a preclinical model of obstructive nephropathy. EXPERIMENTAL APPROACH: To examine the role of JMJD3 in renal fibrosis, we generated mice with global or myeloid cell-specific deletion of JMJD3, and we treated wild-type mice with vehicle or GSK-J4 (selective JMJD3 inhibitor). Mice were subjected to unilateral ureteral obstructive injury to induce renal fibrosis. KEY RESULTS: JMJD3 expression was significantly increased in the kidneys during the development of renal fibrosis, which was associated with an increase in H3K27 dimethylation. Mice with either global or myeloid JMJD3 deficiency exhibited significantly reduced total collagen deposition and extracellular matrix protein production, myeloid fibroblast activation and M2 macrophage polarization in the obstructed kidney. Moreover, IFN regulatory factor 4, a mediator of M2 macrophage polarization, was significantly induced in the obstructed kidneys, which was abolished by JMJD3 deficiency. Furthermore, pharmacological inhibition of JMJD3 with GSK-J4 attenuated kidney fibrosis, reduced myeloid fibroblast activation and suppressed M2 macrophage polarization in the obstructed kidney. CONCLUSION AND IMPLICATIONS: Our study identifies JMJD3 as a critical regulator of myeloid fibroblast activation, macrophage polarization, and renal fibrosis development. Therefore, JMJD3 may represent a promising therapeutic target for chronic kidney disease.


Assuntos
Ativação de Macrófagos , Insuficiência Renal Crônica , Camundongos , Animais , Rim/patologia , Macrófagos/metabolismo , Fibrose , Insuficiência Renal Crônica/metabolismo , Fibroblastos/patologia , Camundongos Endogâmicos C57BL
14.
IEEE J Biomed Health Inform ; 27(8): 3782-3793, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37027577

RESUMO

The morphology and distribution of microcalcifications are the most important descriptors for radiologists to diagnose breast cancer based on mammograms. However, it is very challenging and time-consuming for radiologists to characterize these descriptors manually, and there also lacks of effective and automatic solutions for this problem. We observed that the distribution and morphology descriptors are determined by the radiologists based on the spatial and visual relationships among calcifications. Thus, we hypothesize that this information can be effectively modelled by learning a relationship-aware representation using graph convolutional networks (GCNs). In this study, we propose a multi-task deep GCN method for automatic characterization of both the morphology and distribution of microcalcifications in mammograms. Our proposed method transforms morphology and distribution characterization into node and graph classification problem and learns the representations concurrently. We trained and validated the proposed method in an in-house dataset and public DDSM dataset with 195 and 583 cases,respectively. The proposed method reaches good and stable results with distribution AUC at 0.812 ± 0.043 and 0.873 ± 0.019, morphology AUC at 0.663 ± 0.016 and 0.700 ± 0.044 for both in-house and public datasets. In both datasets, our proposed method demonstrates statistically significant improvements compared to the baseline models. The performance improvements brought by our proposed multi-task mechanism can be attributed to the association between the distribution and morphology of calcifications in mammograms, which is interpretable using graphical visualizations and consistent with the definitions of descriptors in the standard BI-RADS guideline. In short, we explore, for the first time, the application of GCNs in microcalcification characterization that suggests the potential of using graph learning for more robust understanding of medical images.


Assuntos
Neoplasias da Mama , Calcinose , Humanos , Feminino , Mamografia/métodos , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Redes Neurais de Computação , Calcinose/diagnóstico por imagem
15.
BMC Pediatr ; 23(1): 142, 2023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-36997989

RESUMO

OBJECTIVE: Studies have shown that obesity has a significant impact on poor surgical outcomes. However, the relationship between obesity and pediatric epilepsy surgery has not been reported. This study aimed to explore the relationship between obesity and complications of pediatric epilepsy surgery and the effect of obesity on the outcome of pediatric epilepsy surgery, and to provide a reference for weight management of children with epilepsy. METHODS: A single-center retrospective analysis of complications in children undergoing epilepsy surgery was conducted. Body mass index (BMI) percentiles were adjusted by age and used as a criterion for assessing obesity in children. According to the adjusted BMI value, the children were divided into the obese group (n = 16) and nonobese group (n = 20). The intraoperative blood loss, operation time, and postoperative fever were compared between the two groups. RESULTS: A total of 36 children were included in the study, including 20 girls and 16 boys. The mean age of the children was 8.0 years old, ranging from 0.8 to 16.9 years old. The mean BMI was 18.1 kg/m2, ranging from 12.4 kg/m2 to 28.3 kg/m2. Sixteen of them were overweight or obese (44.4%). Obesity was associated with higher intraoperative blood loss in children with epilepsy (p = 0.04), and there was no correlation between obesity and operation time (p = 0.21). Obese children had a greater risk of postoperative fever (56.3%) than nonobese children (55.0%), but this was statistically nonsignificant (p = 0.61). The long-term follow-up outcomes showed that 23 patients (63.9%) were seizure-free (Engel grade I), 6 patients (16.7%) had Engel grade II, and 7 patients (19.4%) had Engel grade III. There was no difference in long-term seizure control outcomes between obese and nonobese groups (p = 0.682). There were no permanent neurological complications after surgery. CONCLUSION: Compared with nonobese children with epilepsy, obese children with epilepsy had a higher intraoperative blood loss. It is necessary to conduct early weight management of children with epilepsy as long as possible.


Assuntos
Epilepsia , Obesidade Infantil , Masculino , Feminino , Humanos , Criança , Lactente , Pré-Escolar , Adolescente , Estudos Retrospectivos , Obesidade Infantil/complicações , Perda Sanguínea Cirúrgica , Sobrepeso/complicações , Epilepsia/complicações , Epilepsia/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Índice de Massa Corporal , Resultado do Tratamento
16.
Interdiscip Sci ; 15(2): 262-272, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36656448

RESUMO

Differentiation of ductal carcinoma in situ (DCIS, a precancerous lesion of the breast) from fibroadenoma (FA) using ultrasonography is significant for the early prevention of malignant breast tumors. Radiomics-based artificial intelligence (AI) can provide additional diagnostic information but usually requires extensive labeling efforts by clinicians with specialized knowledge. This study aims to investigate the feasibility of differentially diagnosing DCIS and FA using ultrasound radiomics-based AI techniques and further explore a novel approach that can reduce labeling efforts without sacrificing diagnostic performance. We included 461 DCIS and 651 FA patients, of whom 139 DCIS and 181 FA patients constituted a prospective test cohort. First, various feature engineering-based machine learning (FEML) and deep learning (DL) approaches were developed. Then, we designed a difference-based self-supervised (DSS) learning approach that only required FA samples to participate in training. The DSS approach consists of three steps: (1) pretraining a Bootstrap Your Own Latent (BYOL) model using FA images, (2) reconstructing images using the encoder and decoder of the pretrained model, and (3) distinguishing DCIS from FA based on the differences between the original and reconstructed images. The experimental results showed that the trained FEML and DL models achieved the highest AUC of 0.7935 (95% confidence interval, 0.7900-0.7969) on the prospective test cohort, indicating that the developed models are effective for assisting in differentiating DCIS from FA based on ultrasound images. Furthermore, the DSS model achieved an AUC of 0.8172 (95% confidence interval, 0.8124-0.8219), indicating that our model outperforms the conventional radiomics-based AI models and is more competitive.


Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Fibroadenoma , Humanos , Feminino , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/patologia , Inteligência Artificial , Diagnóstico Diferencial , Fibroadenoma/diagnóstico por imagem , Fibroadenoma/patologia , Estudos Prospectivos , Neoplasias da Mama/diagnóstico por imagem , Ultrassonografia
17.
Gene Ther ; 30(1-2): 75-87, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35132206

RESUMO

Traumatic brain injury (TBI) survivors suffer from long-term disability and neuropsychiatric sequelae due to irreparable brain tissue destruction. However, there are still few efficient therapies to promote neurorestoration in damaged brain tissue. This study aimed to investigate whether the pro-oncogenic gene ski can promote neurorestoration after TBI. We established a ski-overexpressing experimental TBI mouse model using adenovirus-mediated overexpression through immediate injection after injury. Hematoxylin-eosin staining, MRI-based 3D lesion volume reconstruction, neurobehavioral tests, and analyses of neuronal regeneration and astrogliosis were used to assess neurorestorative efficiency. The effects of ski overexpression on the proliferation of cultured immature neurons and astrocytes were evaluated using imaging flow cytometry. The Ski protein level increased in the perilesional region at 3 days post injury. ski overexpression further elevated Ski protein levels up to 14 days post injury. Lesion volume was attenuated by approximately 36-55% after ski overexpression, with better neurobehavioral recovery, more newborn immature and mature neurons, and less astrogliosis in the perilesional region. Imaging flow cytometry results showed that ski overexpression elevated the proliferation rate of immature neurons and reduced the proliferation rate of astrocytes. These results show that ski can be considered a novel neurorestoration-related gene that effectively promotes neurorestoration, facilitates neuronal regeneration, and reduces astrogliosis after TBI.


Assuntos
Lesões Encefálicas Traumáticas , Gliose , Camundongos , Animais , Gliose/genética , Gliose/metabolismo , Gliose/patologia , Neurônios/metabolismo , Lesões Encefálicas Traumáticas/terapia , Encéfalo/metabolismo , Regeneração
18.
Artigo em Inglês | MEDLINE | ID: mdl-36121961

RESUMO

The precise segmentation of medical images is one of the key challenges in pathology research and clinical practice. However, many medical image segmentation tasks have problems such as large differences between different types of lesions and similar shapes as well as colors between lesions and surrounding tissues, which seriously affects the improvement of segmentation accuracy. In this article, a novel method called Swin Pyramid Aggregation network (SwinPA-Net) is proposed by combining two designed modules with Swin Transformer to learn more powerful and robust features. The two modules, named dense multiplicative connection (DMC) module and local pyramid attention (LPA) module, are proposed to aggregate the multiscale context information of medical images. The DMC module cascades the multiscale semantic feature information through dense multiplicative feature fusion, which minimizes the interference of shallow background noise to improve the feature expression and solves the problem of excessive variation in lesion size and type. Moreover, the LPA module guides the network to focus on the region of interest by merging the global attention and the local attention, which helps to solve similar problems. The proposed network is evaluated on two public benchmark datasets for polyp segmentation task and skin lesion segmentation task as well as a clinical private dataset for laparoscopic image segmentation task. Compared with existing state-of-the-art (SOTA) methods, the SwinPA-Net achieves the most advanced performance and can outperform the second-best method on the mean Dice score by 1.68%, 0.8%, and 1.2% on the three tasks, respectively.

19.
Biomolecules ; 12(8)2022 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-36008975

RESUMO

Colon adenocarcinoma is one of the tumors with the highest mortality rate, and tumorigenesis or development of colon adenocarcinoma is the major reason leading to patient death. However, the molecular mechanism and biomarker to predict tumor progression are currently unclear. With the goal of understanding the molecular mechanism and tumor progression, we utilized the TCGA database to identify differentially expressed genes. After identifying the differentially expressed genes among colon adenocarcinoma tissues with different expression levels of LGR4 and normal tissue, protein-protein interaction, gene ontology, pathway enrichment, gene set enrichment analysis, and immune cell infiltration analysis were conducted. Here, the top 10 hub genes, i.e., ALB, F2, APOA2, CYP1A1, SPRR2B, APOA1, APOB, CYP3A4, SST, and GCG, were identified, and relative correlation analysis was conducted. Kaplan-Meier analysis revealed that higher expression of LGR4 correlates with overall survival of colon adenocarcinoma patients, although expression levels of LGR4 in normal tissues are higher than in tumor tissues. Further functional analysis demonstrated that higher expression of LGR4 in colon adenocarcinoma may be linked to up-regulate metabolism-related pathways, for example, the cholesterol biosynthesis pathway. These results were confirmed by gene set enrichment analysis. Immune cell infiltration analysis clearly showed that the infiltration percentage of T cells was significantly higher than other immune cells, and TIMER analysis revealed a positive correlation between T-cell infiltration and LGR4 expression. Finally, COAD cancer cells, Caco-2, were employed to be incubated with squalene and 25-hydroxycholesterol-3-sulfate, and relative experimental results confirmed that the cholesterol biosynthesis pathway involved in modulating the proliferation of COAD tumorigenesis. Our investigation revealed that LGR4 can be an emerging diagnostic and prognostic biomarker for colon adenocarcinoma by affecting metabolism-related pathways.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Receptores Acoplados a Proteínas G , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Células CACO-2 , Carcinogênese/genética , Colesterol , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Humanos , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo
20.
Comput Math Methods Med ; 2022: 5706341, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35860186

RESUMO

Purpose: To explore the comparison of the reduction of the subtalar articular surface and other postoperative effects of the minimally invasive tarsal sinus approach and lateral L-shaped incision conventional approach for the treatment of calcaneal fracture with 3D printing technology. Methods: Patients who received surgical treatment for calcaneal fractures in the First Affiliated Hospital of Henan University of Science and Technology from June 2019 to December 2020 were collected. 3D printing equipment produced the affected side reduction heel bone fracture model and navigation template model. The tarsal sinus approach was used in the experimental group, and the lateral L-shaped incision approach was used in the control group. Patients were followed up 3 days, 1 month, 3 months, 6 months, and 12 months after the operation. Imaging indicators were measured 12 months after surgery, and scores from American Foot and Ankle Orthopaedic Society (AOFAS) and MSF were performed. Results: Operation time was 70.52 ± 13.16 in the control group and 55.24 ± 12.25 minutes in the experimental group (P < 0.001). Intraoperative blood loss was 98.77 ± 18.65 in the control group and 89.56 + 17.54 in the experimental group (P > 0.05). The duration of antibiotic use was 5.53 ± 3.24 days in the control group and 5.48 ± 4.18 days in the experimental group (P > 0.05). The frequency of fluoroscopy was 6.56 ± 1.72 in the control group and 3.88 ± 1.05 in the experimental group (P < 0.001). Fracture healing time was 3.24 ± 0.52 months in the control group and 3.08 ± 0.58 months in the experimental group (P > 0.05). The postoperative Böhler angle was 28.31 ± 3.14 in the control group and 29.24 ± 2.76 in the experimental group (P > 0.05). Postoperative subtalar articular displacement (step > 2 mm) was observed in 4 patients in the control group and 1 in the experimental group (P < 0.05). MSF score was 90.12 ± 4.85 in the control group and 91.36 ± 2.58 in the experimental group (P > 0.05). Conclusion: The study found that the experimental group was significantly better than the control group in terms of the operation time, intraoperative fluoroscopy times, and success rate of reduction of the subtalar articular surface. 3D printing technology can shorten the operation time, accurately reduce the fracture block, and reduce the secondary trauma, which is conducive to the functional recovery of the affected foot.


Assuntos
Traumatismos do Tornozelo , Calcâneo , Fraturas Ósseas , Traumatismos do Joelho , Calcâneo/diagnóstico por imagem , Calcâneo/cirurgia , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Calcanhar , Humanos , Impressão Tridimensional , Resultado do Tratamento
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