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1.
Angew Chem Int Ed Engl ; : e202417223, 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39373560

RESUMEN

Multimodal upconversion and downshifting circularly polarized luminescent materials hold significant potential for optical anticounterfeiting applications due to their exceptional chiroptical properties. However, constructing these materials within a single emitter remains challenging. In this study, a conceptual model of multimodal up-conversion/downshifting circularly polarized luminescence (CPL) is realized within a single nanoparticle. A new type of nanoparticles with multilayer core-shell architecture is fabricated, capable of delivering upconversion/downshifting luminescence, when excited by a 980 nm laser. Utilizing a co-assembly strategy, multimodal upconversion/downshifting CPL emission, covering a broad emission range from ultraviolet (UV) to the second near-infrared (NIR-II) region, can be realized at the supramolecular level. These chiroptical properties closely follow the chirality of host matrix and are strongly dependent on the distribution mode of nanoparticles within the matrix films. The multimodal upconversion/downshifting CPL behavior enabled cutting-edge encryption applications including optical anticounterfeiting and information encryption. This work introduces a novel approach to designing multimodal upconversion/downshifting CPL materials and opens new avenues for the development of chiroptical functional materials.

2.
Proc Natl Acad Sci U S A ; 121(33): e2405644121, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39121163

RESUMEN

Nuclear factor kappa B (NFκB) is a pathogenic factor in chronic lymphocytic leukemia (CLL) that is not addressed specifically by current therapies. NFκB is activated by inflammatory factors that stimulate toll-like receptors (TLRs) and receptors for interleukin-1 (IL-1) family members. IL-1 is considered a master regulator of inflammation, and IL-1 receptor signaling is inhibited by the IL-1 receptor antagonist anakinra. These considerations suggested that anakinra might have a role in the treatment of CLL. Consistent with this idea, anakinra inhibited spontaneous and TLR7-mediated activation of the canonical NFκB pathway in CLL cells in vitro. However, CLL cells exhibited only weak signaling responses to IL-1 itself, and anakinra was found to inhibit NFκB along with oxidative stress in an IL-1 receptor-independent manner. Anakinra was then administered with minimal toxicity to 11 previously untreated CLL patients in a phase I dose-escalation trial (NCT04691765). A stereotyped clinical response was observed in all patients. Anakinra lowered blood lymphocytes and lymph node sizes within the first month that were associated with downregulation of NFκB and oxidative stress in the leukemia cells. However, inhibition of NFκB was accompanied by upregulation of type 1 interferon (IFN) signaling, c-MYC-regulated genes and proteins, and loss of the initial clinical response. Anakinra increased IFN signaling and survival of CLL cells in vitro that were, respectively, phenocopied by mitochondrial antioxidants and reversed by IFN receptor blocking antibodies. These observations suggest that anakinra has activity in CLL and may be a useful adjunct for conventional therapies as long as compensatory IFN signaling is blocked at the same time.


Asunto(s)
Proteína Antagonista del Receptor de Interleucina 1 , Leucemia Linfocítica Crónica de Células B , FN-kappa B , Transducción de Señal , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Interferones/metabolismo , Proteína Antagonista del Receptor de Interleucina 1/farmacología , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Receptores de Interleucina-1/metabolismo , Receptores de Interleucina-1/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 7/metabolismo , Receptor Toll-Like 7/antagonistas & inhibidores
3.
Cell Death Discov ; 10(1): 314, 2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-38972937

RESUMEN

Kidney fibrosis is considered to be the ultimate aggregation pathway of chronic kidney disease (CKD), but its underlying mechanism remains elusive. Protein kinase C-delta (PKC-δ) plays critical roles in the control of growth, differentiation, and apoptosis. In this study, we found that PKC-δ was highly upregulated in human biopsy samples and mouse kidneys with fibrosis. Rottlerin, a PKC-δ inhibitor, alleviated unilateral ureteral ligation (UUO)-induced kidney fibrosis, inflammation, VDAC1 expression, and cGAS-STING signaling pathway activation. Adeno-associated virus 9 (AAV9)-mediated VDAC1 silencing or VBIT-12, a VDAC1 inhibitor, attenuated renal injury, inflammation, and activation of cGAS-STING signaling pathway in UUO mouse model. Genetic and pharmacologic inhibition of STING relieved renal fibrosis and inflammation in UUO mice. In vitro, hypoxia resulted in PKC-δ phosphorylation, VDAC1 oligomerization, and activation of cGAS-STING signaling pathway in HK-2 cells. Inhibition of PKC-δ, VDAC1 or STING alleviated hypoxia-induced fibrotic and inflammatory responses in HK-2 cells, respectively. Mechanistically, PKC-δ activation induced mitochondrial membrane VDAC1 oligomerization via direct binding VDAC1, followed by the mitochondrial DNA (mtDNA) release into the cytoplasm, and subsequent activated cGAS-STING signaling pathway, which contributed to the inflammation leading to fibrosis. In conclusion, this study has indicated for the first time that PKC-δ is an important regulator in kidney fibrosis by promoting cGAS-STING signaling pathway which mediated by VDAC1. PKC-δ may be useful for treating renal fibrosis and subsequent CKD.

4.
PLoS One ; 19(6): e0299389, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38870184

RESUMEN

Renal fibrosis is the most common pathway in progressive kidney diseases. The unilateral ureteral obstruction (UUO) model is used to induce progressive renal fibrosis. We evaluated the effects of irisin on renal interstitial fibrosis in UUO mice. The GSE121190, GSE36496, GSE42303, and GSE96101 datasets were downloaded from the Gene Expression Omnibus (GEO) database. In total, 656 differentially expressed genes (DEGs) were identified in normal and UUO mouse renal samples. Periostin and matrix metalloproteinase-2 (MMP-2) were selected to evaluate the effect of irisin on renal fibrosis in UUO mice. In UUO mice, irisin ameliorated renal function, decreased the expression of periostin and MMP-2, and attenuated epithelial-mesenchymal transition and extracellular matrix deposition in renal tissues. In HK-2 cells, irisin treatment markedly attenuated TGF-ß1-induced expression of periostin and MMP-2. Irisin treatment also inhibited TGF-ß1-induced epithelial-mesenchymal transition, extracellular matrix formation, and inflammatory responses. These protective effects of irisin were abolished by the overexpression of periostin and MMP-2. In summary, irisin treatment can improve UUO-induced renal interstitial fibrosis through the TGF-ß1/periostin/MMP-2 signaling pathway, suggesting that irisin may be used for the treatment of renal interstitial fibrosis.


Asunto(s)
Moléculas de Adhesión Celular , Transición Epitelial-Mesenquimal , Fibronectinas , Fibrosis , Enfermedades Renales , Metaloproteinasa 2 de la Matriz , Transducción de Señal , Factor de Crecimiento Transformador beta1 , Obstrucción Ureteral , Animales , Obstrucción Ureteral/complicaciones , Obstrucción Ureteral/patología , Obstrucción Ureteral/metabolismo , Obstrucción Ureteral/tratamiento farmacológico , Fibronectinas/metabolismo , Ratones , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/genética , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta1/metabolismo , Moléculas de Adhesión Celular/metabolismo , Moléculas de Adhesión Celular/genética , Transición Epitelial-Mesenquimal/efectos de los fármacos , Masculino , Humanos , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Enfermedades Renales/etiología , Enfermedades Renales/tratamiento farmacológico , Riñón/patología , Riñón/metabolismo , Riñón/efectos de los fármacos , Ratones Endogámicos C57BL , Línea Celular , Modelos Animales de Enfermedad , Periostina
5.
Biomed Eng Online ; 23(1): 52, 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38851691

RESUMEN

Accurate segmentation of multiple organs in the head, neck, chest, and abdomen from medical images is an essential step in computer-aided diagnosis, surgical navigation, and radiation therapy. In the past few years, with a data-driven feature extraction approach and end-to-end training, automatic deep learning-based multi-organ segmentation methods have far outperformed traditional methods and become a new research topic. This review systematically summarizes the latest research in this field. We searched Google Scholar for papers published from January 1, 2016 to December 31, 2023, using keywords "multi-organ segmentation" and "deep learning", resulting in 327 papers. We followed the PRISMA guidelines for paper selection, and 195 studies were deemed to be within the scope of this review. We summarized the two main aspects involved in multi-organ segmentation: datasets and methods. Regarding datasets, we provided an overview of existing public datasets and conducted an in-depth analysis. Concerning methods, we categorized existing approaches into three major classes: fully supervised, weakly supervised and semi-supervised, based on whether they require complete label information. We summarized the achievements of these methods in terms of segmentation accuracy. In the discussion and conclusion section, we outlined and summarized the current trends in multi-organ segmentation.


Asunto(s)
Aprendizaje Profundo , Procesamiento de Imagen Asistido por Computador , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Automatización
6.
Quant Imaging Med Surg ; 14(4): 3086-3106, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38617147

RESUMEN

Background: Parkinson's disease (PD) is an irreversible, chronic degenerative disease of the central nervous system, potentially associated with cerebral white matter (WM) lesions. Investigating the microstructural alterations within the WM in the early stages of PD can help to identify the disease early and enable intervention to reduce the associated serious threats to health. Methods: This study selected 227 cases from the Parkinson's Progression Markers Initiative (PPMI) database, including 152 de novo PD patients and 75 normal controls (NC). Whole-brain voxel analysis of the WM was performed using the tract-based spatial statistics (TBSS) method. The WM regions with statistically significant differences (P<0.05) between the PD and NC groups were identified and used as masks. The mask was applied to each case's fractional anisotropy (FA) image to extract voxel values as feature vectors. Geometric dimensionality reduction was then applied to eliminate redundant values in the feature vectors. Subsequently, the cases were randomly divided into a training group (158 cases, including 103 PD patients and 55 NC) and a test group (69 cases, including 49 PD patients and 20 NC). The least absolute shrinkage and selection operator (LASSO) regression algorithm was employed to extract the minimal set of relevant features, then the random forest (RF) algorithm was utilized for classification using 5-fold cross validation. The resulting model was further integrated with clinical factors to create a comprehensive prediction model. Results: In comparison to the NC group, the FA values in PD patients exhibited a statistically significant decrease (P<0.05), indicating the presence of widespread WM lesions across multiple brain regions. Moreover, the PD prediction model, constructed based on these WM lesion regions, yielded prediction accuracy (ACC) and area under the receiver operating characteristic (ROC) curve (AUC) values of 0.778 and 0.865 in the validation set, and 0.783 and 0.831 in the test set, respectively. Furthermore, the performance of the integrated model showed some improvement, with ACC and AUC values in the test set reaching 0.804 and 0.844, respectively. Conclusions: The quantitative calculation of WM lesion area on FA images using the TBSS method can serve as a neuroimaging biomarker for diagnosing and predicting early PD at the individual level. When integrated with clinical variables, the predictive performance improves.

8.
Ren Fail ; 46(1): 2338933, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38616177

RESUMEN

Thioredoxin-interacting protein (TXNIP) is an important regulatory protein for thioredoxin (TRX) that elicits the generation of reactive oxygen species (ROS) by inhibiting the redox function of TRX. Abundant evidence suggests that TXNIP is involved in the fibrotic process of diabetic kidney disease (DKD). However, the potential mechanism of TXNIP in DKD is not yet well understood. In this study, we found that TXNIP knockout suppressed renal fibrosis and activation of mammalian target of rapamycin complex 1 (mTORC1) and restored transcription factor EB (TFEB) and autophagy activation in diabetic kidneys. Simultaneously, TXNIP interference inhibited epithelial-to-mesenchymal transformation (EMT), collagen I and fibronectin expression, and mTORC1 activation, increased TFEB nuclear translocation, and promoted autophagy restoration in HK-2 cells exposed to high glucose (HG). Rapamycin, an inhibitor of mTORC1, increased TFEB nuclear translocation and autophagy in HK-2 cells under HG conditions. Moreover, the TFEB activators, curcumin analog C1 and trehalose, effectively restored HG-induced autophagy, and abrogated HG-induced EMT and collagen I and fibronectin expression in HK-2 cells. Taken together, these findings suggest that TXNIP deficiency ameliorates renal fibrosis by regulating mTORC1/TFEB-mediated autophagy in diabetic kidney diseases.


Asunto(s)
Nefropatías Diabéticas , Humanos , Autofagia , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Proteínas Portadoras/genética , Colágeno Tipo I , Nefropatías Diabéticas/etiología , Fibronectinas , Fibrosis , Diana Mecanicista del Complejo 1 de la Rapamicina , Tiorredoxinas
9.
Diabetes Metab Syndr Obes ; 17: 75-92, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38196512

RESUMEN

Background: Diabetic kidney disease (DKD) is characterized by renal fibrosis, and the pathogenesis of renal fibrosis is still not definitely confirmed. MiR-204-5p plays an important role in the regulation of fibrosis, autophagy and oxidative stress. In this study, we aimed to investigate the role of miR-204-5p on renal damage in diabetic kidneys and the underlying mechanisms involved. Methods: In vivo, AAV-Ksp-miR-204-5p mimics were injected into mice via tail vein. In vitro, high glucose-induced HK-2 cells were treated with miR-204-5p inhibitor, miR-204-5p mimics, ATG5 siRNA, tertiary butyl hydroquinone (TBHQ), ML385, or 3-Methyladenine (3-MA). FISH and qRT-PCR were used to detect miR-204-5p expression. The expressions of protein and mRNA were detected by Western blotting, immunofluorescence, immunohistochemistry and qRT-PCR. The concentration of fibronectin in HK-2 cells culture medium was detected by ELISA. Results: The expression of miR-204-5p in diabetic kidneys was significantly inhibited than that in control group. Delivering miR-204-5p mimics increased miR-204-5p expression, improved renal function, inhibited renal fibrosis and oxidative stress, and restored autophagy in db/db mice. In vitro, the expression of miR-204-5p was inhibited by HG treatment in HK-2 cells. MiR-204-5p mimics effectively increased miR-204-5p expression and reduced fibronectin and collagen I expression, restored autophagy dysfunction, and increased Nrf2 expression, whereas these alterations were abrogated by Nrf2 inhibitor ML385, autophagy inhibitor 3-methyladenine (3-MA, 5 mM) treatment or ATG5 siRNA transfection in HG-induced HK-2 cells. In addition, miR-204-5p inhibitor significantly inhibited miR-204-5p expression and aggravated HG-induced fibronectin and collagen I expression, autophagy dysfunction, and decreased Nrf2 expression, while these alterations were abolished by Nrf2 activator TBHQ. Furthermore, the binding of miR-204-5p with Keap1 was confirmed by luciferase reporter assay and miR-204-5p negatively regulated Keap1 expression, resulting in the activation of Nrf2 pathway. Conclusion: MicroRNA-204-5p protects against the progression of diabetic renal fibrosis by restoring autophagy via regulating Keap1/Nrf2 pathway.

10.
Int Wound J ; 21(1): e14545, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38272814

RESUMEN

This study aimed to systematically evaluate the impact of evidence-based nursing (EBN) on perioperative wound infections and postoperative complications in patients undergoing surgery for liver hepatocellular carcinoma (LIHC). Randomised controlled trials (RCTs) on the application of EBN on patients receiving LIHC surgery were searched in PubMed, Web of Science, Cochrane Library, Embase, Wanfang, China Biomedical Literature Database and China National Knowledge Infrastructure from the inception of each database to September 2023. Studies were screened and evaluated by two investigators based on inclusion and exclusion criteria, and data were extracted from the final included literature. RevMan 4.0 was used for data analysis. Overall, 15 RCTs involving 1374 patients with LIHC were included, with 687 in the EBN group and 687 in the conventional care group. The analysis revealed that the incidence of wound infections (odds ratio [OR] = 0.32, 95% confidence interval [CI]: 0.18-0.56, p < 0.001) and postoperative complications (OR = 0.22, 95% CI: 0.15-0.31, p < 0.001) was significantly lower in the EBN group than in the conventional care group. The available evidence suggests that nursing strategies for EBN applied in the perioperative period in patients with LIHC receiving surgery can effectively reduce the incidence of wound infections and postoperative complications and promote postoperative recovery.


Asunto(s)
Enfermería Basada en la Evidencia , Neoplasias Hepáticas , Humanos , Infección de la Herida Quirúrgica/etiología , Neoplasias Hepáticas/cirugía , Abdomen , China
11.
Planta Med ; 90(2): 84-95, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37714195

RESUMEN

A brand-new class of interstitial cells, called telocytes, has been detected in the heart. Telocytes can connect and transmit signals to almost all cardiomyocytes; this is highly interrelated with the occurrence and development of heart diseases. Modern studies have shown that berberine has a therapeutic effect on cardiovascular health. However, berberine's mechanism of action on the cardiovascular system through cardiac telocytes is unclear. Interestingly, 5 µm of berberine remarkably decreased the concentration of intracellular calcium and membrane depolarization in cultured telocytes, upregulated the expression of CX43 and ß-catenin, and downregulated the expressions of TRPV4 and TRPV1. Here, telocytes were identified in the vascular adventitia and intima, endocardium, myocardium, adventitia, and heart valves. Moreover, telocytes were broadly dispersed around cardiac vessels and interacted directly through gap junctions and indirectly through extracellular vesicles. Together, cardiac telocytes interact with berberine and then deliver drug information to the heart. Telocytes may be an essential cellular target for drug therapy of the cardiovascular system.


Asunto(s)
Berberina , Telocitos , Animales , Conejos , Berberina/farmacología , Miocardio/metabolismo , Telocitos/metabolismo , Endocardio/metabolismo , Miocitos Cardíacos
12.
Theriogenology ; 215: 312-320, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38128224

RESUMEN

Duck Tembusu virus (DTMUV) is an emerging mosquito-borne flavivirus that infects mainly poultry and has caused huge economic losses to the poultry farming industry in China. Also known as duck hemorrhagic ovarian disease, DTMUV principally destroys ovarian tissue in ducks, causing a dramatic drop in egg production. and can also invade the male reproductive system causing lesions. Currently, little research has been done to reveal the underlying mechanisms of reproductive dysfunction in ducks caused by DTMUV infection. In this study, histopathological analysis and electron microscopy of testes of ducks infected with DTMUV showed that DTMUV caused testicular atrophy and cytoplasmic vacuolation in ducks. Terminal Deoxynucleotidyl Transferase-Mediated Nick-End Labeling (TUNEL) staining and real-time quantitative PCR(RT-qPCR) results further indicated that DTMUV induced spermatogenic cells apoptosis. After DTMUV infection, a large amount of cytochrome c(Cytc) was released from the mitochondrial matrix into the cytoplasm, activating downstream target proteins and causing apoptosis. To sum up, DTMUV induces spermatogenic cell apoptosis through the Cytc-induced mitochondrial apoptosis pathway, our study provides evidence for DTMUV infection-induced male reproductive disorders.


Asunto(s)
Infecciones por Flavivirus , Flavivirus , Enfermedades de las Aves de Corral , Masculino , Animales , Infecciones por Flavivirus/veterinaria , Transducción de Señal , Patos , Apoptosis
14.
Microsc Microanal ; 29(3): 1190-1204, 2023 06 09.
Artículo en Inglés | MEDLINE | ID: mdl-37749671

RESUMEN

Acupuncture can ameliorate or treat diseases according to the meridian theory in traditional Chinese medicine (TCM); however, its mechanism has not been scientifically clarified. On the other hand, telocytes (TCs) are morphologically in accordance with the meridian system, which needs further cytological investigations and acupuncture confirmation. The present study showed that acupuncture could activate TCs in several ways, alleviating rabbit ulcerative colitis. TCs could cytologically communicate the acupoints, the acupuncture sites in skin with their corresponding large intestine by TC homo-cellular junctions, exosomes around TCs, and TC-mediated nerves or blood vessels. TCs expressed transient receptor potential vanilloid type 4, the mechanosensitive channel protein that can transduce the mechanical stimulation of acupuncture into biochemical signals transferring along the extremely thin and long TCs. Collectively, a cellular mechanism diagram of acupuncture was concluded based on TC characteristics. Those results also confirmed the viewpoint that TCs were the key cells of meridian essence in TCM.


Asunto(s)
Terapia por Acupuntura , Colitis Ulcerosa , Meridianos , Telocitos , Animales , Conejos , Colitis Ulcerosa/terapia , Comunicación
15.
Nat Commun ; 14(1): 6123, 2023 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-37777553

RESUMEN

Existing circularly polarized luminescence materials can hardly satisfy the requirements of both large luminescence dissymmetry factor and high luminescent quantum yield, which hinders their practical applications. Here, we present a soft photonic crystal film embedded with chiral nanopores that possesses excellent circularly polarized luminescence performance with a high luminescence dissymmetry factor as well as a large luminescent quantum yield when loaded with various luminescent dyes. Benefitting from the retention of chiral nanopores imprinted from a chiral liquid crystal arrangement, the chiral soft photonic crystal film can not only endow dyes with chiral properties, but also effectively avoid severe aggregation of guest dye molecules. More importantly, the soft photonic crystal film can be recycled many times by loading and eluting guest dye molecules while retaining good stability as well as circularly polarized luminescence performance, enabling various applications, including smart windows, multi-color circularly polarized luminescence and anticounterfeiting.

16.
Microsc Microanal ; 29(5): 1746-1754, 2023 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-37639834

RESUMEN

Electroacupuncture has been generally applied to target obesity, the principle of which is based on the meridian in traditional Chinese medicine. Although Telocytes (TCs) have been reported as the potential essence of meridians, their specific role in the electroacupuncture treatment of obesity remains unclear. Thus, we investigated the cellular evidence for TC-mediated electroacupuncture to alleviate obesity. Mice were divided into three groups as follows: electroacupuncture group (EA), control group (CG), and normal group (NG). The present study showed that the weight of perirenal white adipose tissue (rWAT), the serum level of total cholesterol, and the low-density lipoprotein cholesterol were all significantly decreased after electroacupuncture. Ultrastructurally, the prolongations (telopodes, Tps) of TCs were in direct contact with adipocytes, and lipid droplets were distributed on the surface of Tps. The proportions of double-positive fluorescent areas of TCs (CD34 and PDGFRα) were significantly elevated with concomitant elongated Tps in EA mice, as compared to those in CG mice. The expression of Cx43 and CD63 (gap junction and exosome markers) was significantly enhanced. These characteristics facilitated the transmission of electroacupuncture stimulation from skin to rWAT. We conclude that electroacupuncture relieved obesity by activating TCs morphologically, upregulating the gap junctions between TCs, and increasing the exosomes around TCs.


Asunto(s)
Electroacupuntura , Exosomas , Telocitos , Animales , Ratones , Exosomas/metabolismo , Colesterol/metabolismo
17.
Mod Pathol ; 36(12): 100316, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37634868

RESUMEN

We developed a deep learning framework to accurately predict the lymph node status of patients with cervical cancer based on hematoxylin and eosin-stained pathological sections of the primary tumor. In total, 1524 hematoxylin and eosin-stained whole slide images (WSIs) of primary cervical tumors from 564 patients were used in this retrospective, proof-of-concept study. Primary tumor sections (1161 WSIs) were obtained from 405 patients who underwent radical cervical cancer surgery at the Fudan University Shanghai Cancer Center (FUSCC) between 2008 and 2014; 165 and 240 patients were negative and positive for lymph node metastasis, respectively (including 166 with positive pelvic lymph nodes alone and 74 with positive pelvic and para-aortic lymph nodes). We constructed and trained a multi-instance deep convolutional neural network based on a multiscale attention mechanism, in which an internal independent test set (100 patients, 228 WSIs) from the FUSCC cohort and an external independent test set (159 patients, 363 WSIs) from the Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma cohort of the Cancer Genome Atlas program database were used to evaluate the predictive performance of the network. In predicting the occurrence of lymph node metastasis, our network achieved areas under the receiver operating characteristic curve of 0.87 in the cross-validation set, 0.84 in the internal independent test set of the FUSCC cohort, and 0.75 in the external test set of the Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma cohort of the Cancer Genome Atlas program. For patients with positive pelvic lymph node metastases, we retrained the network to predict whether they also had para-aortic lymph node metastases. Our network achieved areas under the receiver operating characteristic curve of 0.91 in the cross-validation set and 0.88 in the test set of the FUSCC cohort. Deep learning analysis based on pathological images of primary foci is very likely to provide new ideas for preoperatively assessing cervical cancer lymph node status; its true value must be validated with cervical biopsy specimens and large multicenter datasets.


Asunto(s)
Adenocarcinoma , Carcinoma de Células Escamosas , Aprendizaje Profundo , Neoplasias del Cuello Uterino , Femenino , Humanos , Carcinoma de Células Escamosas/patología , Neoplasias del Cuello Uterino/patología , Metástasis Linfática/patología , Estudios Retrospectivos , Eosina Amarillenta-(YS) , Hematoxilina , China , Ganglios Linfáticos/patología , Adenocarcinoma/patología
18.
Diagnostics (Basel) ; 13(13)2023 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-37443644

RESUMEN

BACKGROUND: Clinically, physicians diagnose portal vein diseases on abdominal CT angiography (CTA) images scanned in the hepatic arterial phase (H-phase), portal vein phase (P-phase) and equilibrium phase (E-phase) simultaneously. However, existing studies typically segment the portal vein on P-phase images without considering other phase images. METHOD: We propose a method for segmenting portal veins on multiphase images based on unsupervised domain transfer and pseudo labels by using annotated P-phase images. Firstly, unsupervised domain transfer is performed to make the H-phase and E-phase images of the same patient approach the P-phase image in style, reducing the image differences caused by contrast media. Secondly, the H-phase (or E-phase) image and its style transferred image are input into the segmentation module together with the P-phase image. Under the constraints of pseudo labels, accurate prediction results are obtained. RESULTS: This method was evaluated on the multiphase CTA images of 169 patients. The portal vein segmented from the H-phase and E-phase images achieved DSC values of 0.76 and 0.86 and Jaccard values of 0.61 and 0.76, respectively. CONCLUSION: The method can automatically segment the portal vein on H-phase and E-phase images when only the portal vein on the P-phase CTA image is annotated, which greatly assists in clinical diagnosis.

19.
Poult Sci ; 102(9): 102891, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37454644

RESUMEN

The Duck Tembusu virus (DTMUV) is a zoonotic flavivirus characterized by nonsuppurative encephalitis and decreasing egg production that has adversely affected the poultry industry. While the way of invasion of DTMUV into different host cells, especially primary cells, remains elusive. In the present study, the ultrastructural pathological characteristics showed that DTMUV underwent a typical maturation and replication process: progeny virus particles gathered in rough endoplasmic reticulum (RER) cisternae, reached the cell membrane via Golgi body's endocrine channel, then were released in the infected baby hamster kidney-21 (BHK-21) and duck embryo fibroblast (DEF). Endoplasmic reticulum vesicles in BHK-21 were short rods and densely arranged like honeycombs, whereas vesicles in DEF were round and dispersed. Further study showed that the virus replication peak in mammalian BHK-21 cells was at 48 hpi, whereas in avian DEF cells was at 24 hpi. DTMUV entry into BHK-21 and DEF cells was blocked by clathrin inhibitor, chlorpromazine (CPZ), indicating that the flavivirus DTMUV enters BHK-21 and DEF both via a clathrin-mediated endocytosis (CME) pathway rather than caveola-mediated endocytosis or micropinocytosis. The endocytic difference in DTMUV entry into BHK-21 and DEF cells might provide insight into understanding the underlying virulence difference between passaged cells and cultured cells.


Asunto(s)
Flavivirus , Enfermedades de las Aves de Corral , Cricetinae , Animales , Patos/metabolismo , Pollos/metabolismo , Endocitosis , Fibroblastos , Clatrina/metabolismo , Riñón/metabolismo , Mamíferos/metabolismo
20.
Front Neurosci ; 17: 1203823, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37360174

RESUMEN

Background: Sarcopenia is generally diagnosed by the total area of skeletal muscle in the CT axial slice located in the third lumbar (L3) vertebra. However, patients with severe liver cirrhosis cannot accurately obtain the corresponding total skeletal muscle because their abdominal muscles are squeezed, which affects the diagnosis of sarcopenia. Purpose: This study proposes a novel lumbar skeletal muscle network to automatically segment multi-regional skeletal muscle from CT images, and explores the relationship between cirrhotic sarcopenia and each skeletal muscle region. Methods: This study utilizes the skeletal muscle characteristics of different spatial regions to improve the 2.5D U-Net enhanced by residual structure. Specifically, a 3D texture attention enhancement block is proposed to tackle the issue of blurred edges with similar intensities and poor segmentation between different skeletal muscle regions, which contains skeletal muscle shape and muscle fibre texture to spatially constrain the integrity of skeletal muscle region and alleviate the difficulty of identifying muscle boundaries in axial slices. Subsequentially, a 3D encoding branch is constructed in conjunction with a 2.5D U-Net, which segments the lumbar skeletal muscle in multiple L3-related axial CT slices into four regions. Furthermore, the diagnostic cut-off values of the L3 skeletal muscle index (L3SMI) are investigated for identifying cirrhotic sarcopenia in four muscle regions segmented from CT images of 98 patients with liver cirrhosis. Results: Our method is evaluated on 317 CT images using the five-fold cross-validation method. For the four skeletal muscle regions segmented in the images from the independent test set, the avg. DSC is 0.937 and the avg. surface distance is 0.558 mm. For sarcopenia diagnosis in 98 patients with liver cirrhosis, the cut-off values of Rectus Abdominis, Right Psoas, Left Psoas, and Paravertebral are 16.67, 4.14, 3.76, and 13.20 cm2/m2 in females, and 22.51, 5.84, 6.10, and 17.28 cm2/m2 in males, respectively. Conclusion: The proposed method can segment four skeletal muscle regions related to the L3 vertebra with high accuracy. Furthermore, the analysis shows that the Rectus Abdominis region can be used to assist in the diagnosis of sarcopenia when the total muscle is not available.

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