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1.
Turk J Gastroenterol ; 35(1): 41-47, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38454276

RESUMO

BACKGROUND/AIMS: The aim of this study was to explore the risk factors for the incidence of gastroscopy-assisted capsule endoscopy and the small bowel transit time in pediatric patients who underwent capsule endoscopy examination. MATERIALS AND METHODS: A retrospective analysis was performed to analyze the clinical data collected from pediatric patients who underwent capsule endoscopy examination. RESULTS: A total of 239 pediatric patients were enrolled in this study. About 196 (82.0%) patients completed the entire small bowel capsule endoscopy examination, while 3 (1.3%) patients were subjected to capsule retention. Only age, not gender, height, body weight, body mass index, chief complaint, and intestinal preparation medications, has been identified as a risk factor for the incidence of gastroscopy-assisted capsule endoscopy (P < .05) by multivariate logistic regression. Further analysis showed that the small bowel transit time in the self-swallowed group was shorter than that in the gastroscopy-assisted group, while no significant difference was obtained in other factors, including intestinal preparation medications, metoclopramide, and lesions in the small intestine, which did not significantly affect small bowel transit time compared with the corresponding control group (P > .05). CONCLUSION: A comprehensive assessment is required before performing capsule endoscopy, because age has been identified as a critical risk factor for the incidence of gastroscopy-assisted capsule endoscopy in pediatric patients.


Assuntos
Endoscopia por Cápsula , Humanos , Criança , Estudos Retrospectivos , Gastroscopia , Intestino Delgado/patologia , Fatores de Risco
2.
J Cancer Res Clin Oncol ; 150(2): 93, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38369672

RESUMO

PURPOSE: Precise identification of lymph node metastases is vital for the management of cervical cancer. However, the existing diagnostic methods for lymph node metastases have certain drawbacks. In this study, we aim to explore the expression of cancer-associated fibroblasts (CAFs) and tumor-to-stroma CD8+ T cells ratio (CD8+ T cells T:S ratio) and its association with lymph node metastases of cervical cancer. METHODS: Hundred and ten cervical cancer tissues and 39 biopsy tissues from patients were investigated immunocytochemically for the expression of CAFs and CD8+ T cells. The statistical correlation analysis was carried out using the SPSS system. RESULTS: A strong and statistically significant negative correlation (r= - 0.690; P < 0.001) was observed between CAF density and CD8+ T cells T:S ratio. Not only were CAFs density and CD8+ T cells T:S ratio correlated with lymph node metastases respectively (P < 0.001), but the combination of them also significantly correlated with lymph node metastases (P < 0.001). Then, we constructed the combined diagnosis model (Logit (P) = - 4.446 + 0.300 × CAFs + 0.752 × CD8+ T cells T:S Ratio) of cervical cancer lymph node metastases. ROC curves analysis showed that the ROC curves areas for CAFs, CD8+ T cells T:S ratio, and a combination of both are 0.879, 0.747, and 0.951. Then, the prediction model was verified by biopsy specimens and consistent results were obtained. CONCLUSIONS: The combination of CAF density and CD8+ T cells T:S ratio has a significant predictive value for lymph node metastases in patients with cervical cancer.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias do Colo do Útero , Feminino , Humanos , Metástase Linfática/patologia , Neoplasias do Colo do Útero/patologia , Fibroblastos Associados a Câncer/metabolismo , Linfócitos T CD8-Positivos/patologia , Biópsia , Linfonodos/patologia
3.
Tzu Chi Med J ; 36(1): 46-52, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38406567

RESUMO

Achilles tendon rupture is a common and primary cause of lower limb tendon injury suffered during sports-related activities. The causes of Achilles tendon rupture include the calf muscle and tendon overuse, poor tendon quality, and various medical conditions. Historically, acute Achilles tendon rupture was treated conservatively. However, historical techniques are now associated with an increased risk of rerupture. To address this problem, open repair has been proposed. Open repair is associated with a reduced risk of rerupture; however, it is also closely associated with wound complications, like wound infection, whose treatment is time-consuming and costly. Therefore, minimally invasive Achilles tendon repair has been proposed as a promising option with acceptable functional outcomes. Nevertheless, despite its benefits, minimally invasive Achilles tendon repair is associated with increased risks of sural nerve injury and rerupture. In this review, we evaluate the currently used treatment strategies for acute Achilles tendon rupture and their historical evolution to provide evidence-based recommendations for physicians.

4.
Orthop J Sports Med ; 12(1): 23259671231218649, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38274016

RESUMO

Background: The arthroscopic Broström technique with or without Gould modification has been used to treat patients with anterior talofibular ligament injury who failed nonoperative management and progressed to chronic lateral ankle instability. However, some patients develop limited range of motion over the ankle joint postoperatively. Purpose/Hypothesis: To compare the clinical outcomes and midterm functional performance of knot-tying techniques between using a knot pusher and a semiconstrained freehand tie during arthroscopic Broström-Gould procedure with inferior extensor retinaculum (IER) augmentation. It was hypothesized that the semiconstrained freehand tie would provide better plantarflexion of the ankle joint compared with the knot pusher. Study Design: Cohort study; Level of evidence, 3. Methods: Included were 135 consecutive patients with mild-to-moderate lateral ankle instability (mean age, 42.7 years; range, 16-78 years) who underwent an arthroscopic Broström-Gould procedure from March 1, 2016, to April 30, 2022. The patients were divided into 2 groups according to the tying technique used in the Gould modification: surgical tie using a knot pusher (KP group; n = 30) or a semiconstrained freehand tie (FT group; n = 105). Radiographic parameters and ultrasound dynamic testing were examined during the preoperative assessment. Preoperative and 2-year postoperative assessments comprised American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale, visual analog scale for pain, and 12-Item Short Form Survey (SF-12) scores. Results: The 2 groups had no differences in age, sex, or severity distribution in the preoperative assessment. American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale, visual analog scale pain, and SF-12 scores were significantly better at the postoperative evaluation (all P < .05) in both groups. No significant difference was noted between groups in outcome scores. In the KP group, however, 7 out of 30 patients (23.3%) developed ankle stiffness with tightness when performing plantarflexion movement. No patients in the FT group reported similar symptoms. Conclusion: For mild-to-moderate chronic lateral ankle instability, we propose an arthroscopic Broström procedure with the addition of IER augmentation using a semiconstrained freehand tie to avoid overtightening the IER. This ensures favorable patient satisfaction and clinical outcomes without limitation of plantarflexion of the ankle joint and avoids the possible complication of stiffness with plantarflexion.

5.
Acta Biomater ; 174: 281-296, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37951519

RESUMO

RNA interference (RNAi) presents great potential against intractable liver diseases. However, the establishment of specific, efficient, and safe delivery systems targeting hepatocytes remains a great challenge. Herein, we described a promising hepatocytes-targeting system through integrating triantennary N-acetylgalactosamine (GalNAc)-engineered cell membrane with biodegradable mesoporous silica nanoparticles, which efficiently and safely delivered siRNA to hepatocytes and silenced the target PCSK9 gene expression for the treatment of non-alcoholic fatty liver disease. Having optimized the GalNAc-engineering strategy, insertion orders, and cell membrane source, we obtained the best-performing GalNAc-formulations allowing strong hepatocyte-specific internalization with reduced Kupffer cell capture, resulting in robust gene silencing and less hepatotoxicity when compared with cationic lipid-based GalNAc-formulations. Consequently, a durable reduction of lipid accumulation and damage was achieved by systemic administering siRNAs targeting PCSK9 in high-fat diet-fed mice, accompanied by displaying desirable safety profiles. Taken together, this GalNAc-engineering biomimetics represented versatile, efficient, and safe carriers for the development of hepatocyte-specific gene therapeutics, and prevention of metabolic diseases. STATEMENT OF SIGNIFICANCE: Compared to MSN@LP-GN3 (MC3-LNP), MSN@CM-GN3 exhibited strong hepatocyte targeting and Kupffer cell escaping, as well as good biocompatibility for safe and efficient siRNA delivery. Furthermore, siPCSK9 delivered by MSN@CM-GN3 reduced both serum and liver LDL-C, TG, TC levels and lipid droplets in HFD-induced mice, resulting in better performance than MSN/siPCSK9@LP-GN3 in terms of lipid-lowering effect and safety profiles. These findings indicated promising advantages of our biomimetic GN3-based systems for hepatocyte-specific gene delivery in chronic liver diseases. Our work addressed the challenges associated with the lower targeting efficiency of cell membrane-mimetic drug delivery systems and the immunogenicity of traditional GalNAc delivery systems. In conclusion, this study provided an effective and versatile approach for efficient and safe gene editing using ligand-integrated biomimetic nanoplatforms.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Pró-Proteína Convertase 9 , Camundongos , Animais , Interferência de RNA , Pró-Proteína Convertase 9/genética , Pró-Proteína Convertase 9/metabolismo , Pró-Proteína Convertase 9/farmacologia , Hepatopatia Gordurosa não Alcoólica/terapia , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Biomimética , Hepatócitos/metabolismo , Fígado/metabolismo , RNA Interferente Pequeno/farmacologia , Lipídeos/farmacologia
6.
Biomater Adv ; 156: 213722, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38101076

RESUMO

Noninvasive lung drug delivery is critical for treating respiratory diseases. Pluronic-based copolymers have been used as multifunctional materials for medical and biological applications. However, the Pluronic F127-based hydrogel is rapidly degraded, adversely affecting the mechanical stability for prolonged drug release. Therefore, this study designed two thermosensitive copolymers by modifying the Pluronic F127 terminal groups with carboxyl (ADF127) or amine groups (EDF127) to improve the viscosity and storage modulus of drug formulations. ß-alanine and ethylenediamine were conjugated at the terminal of Pluronic F127 using a two-step acetylation process, and the final copolymers were characterized using 1H nuclear magnetic resonance (1H NMR) and Fourier-transform infrared spectra. According to the 1H NMR spectra, Pluronic F127 was functionalized to form ADF127 and EDF127 with 85 % and 71 % functionalization degrees, respectively. Rheological studies revealed that the ADF127 (15 wt%) and EDF127 (15 wt%) viscosities increased from 1480 Pa.s (Pluronic F127) to 1700 Pa.s and 1800 Pa.s, respectively. Furthermore, the elastic modulus of ADF127 and EDF127 increased, compared with that of native Pluronic F127 with the addition of 5 % mucin, particularly for ADF127, thereby signifying the stronger adhesive nature of ADF127 and EDF127 with mucin. Additionally, ADF127 and EDF127 exhibited a decreased gelation temperature, decreasing from 33 °C (Pluronic F127 at 15 wt%) to 24 °C. Notably, the in vitro ADF127 and EDF127 drug release was prolonged (95 %; 48 h) by the hydrogel encapsulation of the liposome-Bdph combined with mucin, and the intermolecular hydrogen bonding between the mucin and the hydrogel increased the retention time and stiffness of the hydrogels. Furthermore, ADF127 and EDF127 incubated with NIH-3T3 cells exhibited biocompatibility within 2 mg/mL, compared with Pluronic F127. The nasal administration method was used to examine the biodistribution of the modified hydrogel carrying liposomes or exosomes with fluorescence using the IVIS system. Drug accumulation in the lungs decreased in the following order: ADF127 > EDF127 > liposomes or exosomes alone. These results indicated that the carboxyl group-modified Pluronic F127 enabled well-distributed drug accumulation in the lungs, which is beneficial for intranasal administration routes in treating diseases such as lung fibrosis.


Assuntos
Lipossomos , Poloxâmero , Camundongos , Animais , Poloxâmero/química , Hidrogéis , Mucinas , Distribuição Tecidual , Polímeros , Pulmão
7.
bioRxiv ; 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38045396

RESUMO

The human cerebral cortex is organized into functionally segregated but synchronized regions connected by the structural connectivity of white matter pathways. While the structure-function coupling has been implicated in cognitive development and neuropsychiatric disorders, it remains unclear to what extent the coupling reflects a group-common characteristic or varies across individuals at global and regional levels. Leveraging two independent, high-quality datasets, we found that the graph neural network predicted unseen individuals' functional connectivity from structural connectivity more accurately than previous studies, reflecting a strong structure-function coupling. This coupling was primarily driven by network topology and was substantially stronger than linear models. We also found that structure-function coupling was dominated by the group-common effects, with subtle yet significant individual-specific effects. The regional group and individual effects in the coupling were both hierarchically organized across the cortex along a sensorimotor-association cortical axis, with lower group effects and higher individual effects in association cortices. These findings emphasize the importance of considering the group and individual effects in cortical structure-function coupling, suggesting insights into connectivity-guided therapeutics.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38161195

RESUMO

A patient-friendly and efficient treatment method for patients with spinocerebellar ataxia type 3 (SCA3) was provided through a nose-to-brain liposomal system. Initially, PGK1 was overexpressed in HEK 293-84Q-GFP diseased cells (HEK 293-84Q-GFP-PGK1 cells) to confirm its effect on the diseased protein polyQ. A decrease in polyQ expression was demonstrated in HEK 293-84Q-GFP-PGK1 cells compared to HEK 293-84Q-GFP parental cells. Subsequently, PGK1 was encapsulated in a liposomal system to evaluate its therapeutic efficiency in SCA3. The optimized liposomes exhibited a significantly enhanced positive charge, facilitating efficient intracellular protein delivery to the cells. The proteins were encapsulated within the liposomes using an optimized method involving a combination of heat shock and sonication. The liposomal system was further demonstrated to be deliverable to the brain via intranasal administration. PGK1/liposomes were intranasally delivered to SCA3 mice, which subsequently exhibited an amelioration of motor impairment, as assessed via the accelerated rotarod test. Additionally, fewer shrunken morphology Purkinje cells and a reduction in polyQ expression were observed in SCA3 mice that received PGK1/liposomes but not in the untreated, liposome-only, or PGK1-only groups. This study provides a non-invasive route for protein delivery and greater delivery efficiency via the liposomal system for treating neurodegenerative diseases.

9.
Turk J Gastroenterol ; 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37966265

RESUMO

BACKGROUND/AIMS: The aim of this study was to explore the risk factors for the incidence of gastroscopy-assisted capsule endoscopy and the small bowel transit time in pediatric patients who underwent capsule endoscopy examination. MATERIALS AND METHODS: A retrospective analysis was performed to analyze the clinical data collected from pediatric patients who underwent capsule endoscopy examination. RESULTS: A total of 239 pediatric patients were enrolled in this study. About 196 (82.0%) patients completed the entire small bowel capsule endoscopy examination, while 3 (1.3%) patients were subjected to capsule retention. Only age, not gender, height, body weight, body mass index, chief complaint, and intestinal preparation medications, has been identified as a risk factor for the incidence of gastroscopy-assisted capsule endoscopy (P < .05) by multivariate logistic regression. Further analysis showed that the small bowel transit time in the self-swallowed group was shorter than that in the gastroscopy-assisted group, while no significant difference was obtained in other factors, including intestinal preparation medications, metoclopramide, and lesions in the small intestine, which did not significantly affect small bowel transit time compared with the corresponding control group (P > .05). CONCLUSION: A comprehensive assessment is required before performing capsule endoscopy, because age has been identified as a critical risk factor for the incidence of gastroscopy-assisted capsule endoscopy in pediatric patients.

10.
Front Immunol ; 14: 1270411, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38022496

RESUMO

Background: Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder affecting millions worldwide. Due to the complexity of its pathogenesis, the treatment options for IBD are limited. This study focuses on ELF4, a member of the ETS transcription factor family, as a target to elucidate its role in IBD and investigate its mechanism of action in alleviating IBD symptoms by activating IL1RN transcription to suppress the activity of inflammatory TH17 cells. Methods: Using the GEO database, this study examined LPS-induced intestinal inflammatory genes and their regulation mechanisms. We examined the colon length of LPS-treated mice and derived the Disease Activity Index (DAI). H&E staining, ELISA, and flow cytometry were used to detect mice colon tissue damage, inflammatory factor levels in mouse serum, mouse macrophage types and inflammatory TH17 cell activity. RT-qPCR and Western blot detected ELF4, IL1RN, M1, and M2 polarization markers. In Vitro, using dual-luciferase and ChIP assays, we tested mouse bone marrow-derived macrophages (BMDMs) and mouse intestinal epithelial cells for IL1RN promoter activity and ELF4 enrichment. Results: Bioinformatics showed that LPS-induced colitis animals have reduced ELF4 expression in their colon tissue. In vivo tests confirmed reduced ELF4 expression in mice with LPS-induced colitis. ELF4 overexpression reduced mouse intestinal inflammation. ELF4 activated IL1RN transcription in bioinformatics and in vitro tests. ELF4 promoted IL1RN transcription and macrophage M2 polarization to limit intestinal epithelial cell death and inflammation and reduce mouse intestinal inflammation in vitro. ELF4 also reduced the Th17/Treg ratio by increasing IL1RN transcription. Conclusion: ELF4 activates IL1RN transcription, suppresses inflammatory TH17 cells, and induces macrophage M2 polarization to treat IBD.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Animais , Camundongos , Diferenciação Celular/genética , Colite/induzido quimicamente , Inflamação/genética , Inflamação/metabolismo , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/metabolismo , Lipopolissacarídeos/efeitos adversos , Macrófagos/metabolismo , Células Th17 , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
11.
Gen Psychiatr ; 36(5): e101133, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37859750

RESUMO

Background: Youth suicide has been a pressing public mental health concern in China, yet there is a lack of gatekeeper intervention programmes developed locally to prevent suicide among Chinese adolescents. Aims: The current Delphi study was the first step in the systematic development of the Life Gatekeeper programme, the first gatekeeper programme to be developed locally in China that aims to equip teachers and parents with the knowledge, skills and ability to identify and intervene with students at high risk of suicide. Methods: The Delphi method was used to elicit a consensus of experts who were invited to evaluate the importance of training content, the feasibility of the training delivery method, the possibility of achieving the training goals and, finally, the appropriateness of the training materials. Two Delphi rounds were conducted among local experts with diversified professional backgrounds in suicide research and practice. Statements were accepted for inclusion in the adjusted training programme if they were endorsed by at least 80% of the panel. Results: Consensus was achieved on 201 out of 207 statements for inclusion into the adapted guidelines for the gatekeeper programme, with 151 from the original questionnaire and 50 generated from comments of the panel members. These endorsed statements were synthesised to develop the content of the Life Gatekeeper training programme. Conclusions: This Delphi study provided an evidence base for developing the first gatekeeper training programme systematically and locally in China. We hope that the current study can pave the way for more evidence-based suicide prevention programmes in China. Further study is warranted to evaluate the effectiveness of the Life Gatekeeper training programme.

12.
Comput Biol Med ; 166: 107517, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37778214

RESUMO

Electroencephalogram (EEG) signal contains important information about abnormal brain activity, which has become an important basis for epilepsy diagnosis. Recently, epilepsy EEG signal classification methods mainly extract features from the perspective of a single domain, which cannot effectively utilize the spatial domain information in EEG signals. The redundant information in EEG signals will affect the learning features with the increase of convolution layer and multi-domain features, resulting in inefficient learning and a lack of distinguishing features. To tackle these issues, we propose an end-to-end 3D convolutional multiband seizure-type classification model based on attention mechanisms. Specifically, to process preprocessed electroencephalogram (EEG) data, a multilevel wavelet decomposition is applied to obtain the joint distribution information in the two-dimensional time-frequency domain across multiple frequency bands. Subsequently, this information is transformed into three-dimensional spatial data based on the electrode configuration. Discriminative joint activity features in the time, frequency, and spatial domains are then extracted by a series of parallel 3D convolutional sub-networks, where 3D channels and spatial attention mechanisms improve the ability to learn critical global and local information. A multi-layer perceptron is finally implemented to integrate the extracted features and further map them to the classification results. Experimental results on the TUSZ dataset, the world's largest publicly available seizure corpus, show that 3D-CBAMNet significantly outperforms the state-of-the-art methods, indicating effectiveness in the seizure type classification task.

13.
Eur J Pharm Sci ; 191: 106608, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37832855

RESUMO

Exosome therapy is a novel trend in regeneration medicine. However, identifying a suitable biomarker that can associate the therapeutic efficacy of exosomes with SCA3/MJD is essential. In this study, parental cells were preconditioned with butylidenephthalide (Bdph) for exosome preparation to evaluate the therapeutic effect of SCA3/MJD. The therapeutic agent hsa-miRNA-6780-5p was enriched up to 98-fold in exosomes derived from butylidenephthalide (Bdph)-preconditioned human olfactory ensheathing cells (hOECs) compared with that in naïve hOECs exosomes. The particle sizes of exosomes derived from naïve hOECs and those derived from hOECs preconditioned with Bdph were approximately 113.0 ± 3.5 nm and 128.9 ± 0.7 nm, respectively. A liposome system was used to demonstrate the role of hsa-miRNA-6780-5p, wherein hsa-miRNA-6780-5p was found to enhance autophagy and inhibit the expression of spinocerebellar ataxia type 3 (SCA3) disease proteins with the polyglutamine (polyQ) tract. Exosomes with enriched hsa-miRNA-6780-5p were further applied to HEK-293-84Q cells, leading to decreased expression of polyQ and increased autophagy. The results were reversed when 3MA, an autophagy inhibitor, was added to the cells treated with hsa-miRNA-6780-5p-enriched exosomes, indicating that the decreased polyQ expression was modulated via autophagy. SCA3 mice showed improved motor coordination behavior when they intracranially received exosomes enriched with hsa-miRNA-6780-5p. SCA3 mouse cerebellar tissues treated with hsa-miRNA-6780-5p-enriched exosomes showed decreased expression of polyQ and increased expression of LC3II/I, an autophagy marker. In conclusion, our findings can serve as a basis for developing an alternative therapeutic strategy for SCA3 disease treatment using miRNA-enriched exosomes derived from chemically preconditioned cells.


Assuntos
Exossomos , Doença de Machado-Joseph , MicroRNAs , Humanos , Camundongos , Animais , Doença de Machado-Joseph/tratamento farmacológico , Doença de Machado-Joseph/metabolismo , Exossomos/metabolismo , Células HEK293 , MicroRNAs/metabolismo
14.
Asian J Psychiatr ; 89: 103755, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37672951

RESUMO

To combat the pressing issue of contemporary suicide rates, an effective Life Gatekeeper training program was developed to educate school teachers in identifying and intervening with at-risk students. Two single-arm sequential studies evaluated the program's effectiveness, spanning implementation science stages from design to refinement. The initial study employed face-to-face training (FTF), followed by a standardized video-based 'Train-the-trainer' (TTT) approach. In Study 1, post-intervention and one-month follow-up results showed improved suicide literacy, reduced stigma, and increased willingness to intervene among gatekeepers. The revised TTT program (study 2) also yielded reduced stigmatization and improved intervention competence. In addition, six out of twenty teachers exhibited gatekeeper behaviors. In conclusion, both delivery methods proved effective, particularly the practical application of the TTT version, although further research is warranted to examine long-term effectiveness of the program.


Assuntos
População do Leste Asiático , Prevenção ao Suicídio , Suicídio , Adolescente , Humanos , Professores Escolares , Estudantes
15.
Artigo em Inglês | MEDLINE | ID: mdl-37669211

RESUMO

High-resolution ultrasound shear wave elastography has been used to determine the mechanical properties of hand tendons. However, because of fiber orientation, tendons have anisotropic properties; this results in differences in shear wave velocity (SWV) between ultrasound scanning cross sections. Rotating transducers can be used to achieve full-angle scanning. However, this technique is inconvenient to implement in clinical settings. Therefore, in this study, high-frequency ultrasound (HFUS) dual-direction shear wave imaging (DDSWI) based on two external vibrators was used to create both transverse and longitudinal shear waves in the human flexor carpi radialis tendon. SWV maps from two directions were obtained using 40-MHz ultrafast imaging at the same scanning cross section. The anisotropic map was calculated pixel by pixel, and 3-D information was obtained using mechanical scanning. A standard phantom experiment was then conducted to verify the performance of the proposed HFUS DDSWI technique. Human studies were also conducted where volunteers assumed three hand postures: relaxed (Rel), full fist (FF), and tabletop (TT). The experimental results indicated that both the transverse and longitudinal SWVs increased due to tendon flexion. The transverse SWV surpassed the longitudinal SWV in all cases. The average anisotropic ratios for the Rel, FF, and TT hand postures were 1.78, 2.01, and 2.21, respectively. Both the transverse and the longitudinal SWVs were higher at the central region of the tendon than at the surrounding region. In conclusion, the proposed HFUS DDSWI technique is a high-resolution imaging technique capable of characterizing the anisotropic properties of tendons in clinical applications.


Assuntos
Técnicas de Imagem por Elasticidade , Tendões , Humanos , Anisotropia , Tendões/diagnóstico por imagem , Ultrassonografia/métodos , Técnicas de Imagem por Elasticidade/métodos , Imagens de Fantasmas
16.
ACS Appl Mater Interfaces ; 15(34): 40864-40876, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37603418

RESUMO

Biofilm infections are associated with most human bacterial infections and are prone to bacterial multidrug resistance. There is an urgent need to develop an alternative approach to antibacterial and antibiofilm agents. Herein, two positively charged semiconductor conjugated polymer nanoparticles (SPPD and SPND) were prepared for additive antibacterial and antibiofilm activities with the aid of positive charge and photothermal therapy (PTT). The positive charge of SPPD and SPND was helpful in adhering to the surface of bacteria. With an 808 nm laser irradiation, the photothermal activity of SPPD and SPND could be effectively transferred to bacteria and biofilms. Under the additive effect of positive charge and PTT, the inhibition rate of Staphylococcus aureus (S. aureus) treated with SPPD and SPND (40 µg/mL) could reach more than 99.2%, and the antibacterial activities of SPPD and SPND against S. aureus biofilms were 93.5 and 95.8%. SPPD presented better biocompatibility than SPND and exhibited good antibiofilm properties in biofilm-infected mice. Overall, this additive treatment strategy of positive charge and PTT provided an optional approach to combat biofilms.


Assuntos
Nanoestruturas , Infecções Estafilocócicas , Humanos , Animais , Camundongos , Staphylococcus aureus , Semicondutores , Antibacterianos/farmacologia , Biofilmes , Polímeros/farmacologia , Infecções Estafilocócicas/tratamento farmacológico
17.
Front Med (Lausanne) ; 10: 1160013, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37547611

RESUMO

Background: Predicting physical function upon discharge among hospitalized older adults is important. This study has aimed to develop a prediction model of physical function upon discharge through use of a machine learning algorithm using electronic health records (EHRs) and comprehensive geriatrics assessments (CGAs) among hospitalized older adults in Taiwan. Methods: Data was retrieved from the clinical database of a tertiary medical center in central Taiwan. Older adults admitted to the acute geriatric unit during the period from January 2012 to December 2018 were included for analysis, while those with missing data were excluded. From data of the EHRs and CGAs, a total of 52 clinical features were input for model building. We used 3 different machine learning algorithms, XGBoost, random forest and logistic regression. Results: In total, 1,755 older adults were included in final analysis, with a mean age of 80.68 years. For linear models on physical function upon discharge, the accuracy of prediction was 87% for XGBoost, 85% for random forest, and 32% for logistic regression. For classification models on physical function upon discharge, the accuracy for random forest, logistic regression and XGBoost were 94, 92 and 92%, respectively. The auROC reached 98% for XGBoost and random forest, while logistic regression had an auROC of 97%. The top 3 features of importance were activity of daily living (ADL) at baseline, ADL during admission, and mini nutritional status (MNA) during admission. Conclusion: The results showed that physical function upon discharge among hospitalized older adults can be predicted accurately during admission through use of a machine learning model with data taken from EHRs and CGAs.

18.
Mediterr J Hematol Infect Dis ; 15(1): e2023040, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37435035

RESUMO

Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid clonal diseases that are characterized by ineffective bone marrow hematopoiesis. Since studies have confirmed the significance of miRNAs in ineffective hematopoiesis in MDS, the current report elucidated the mechanism mediated by miR-155-5p. The bone marrow of MDS patients was collected to detect miR-155-5p and to analyze the correlation between miR-155-5p and clinicopathological variables. Isolated bone marrow CD34+ cells were transfected with lentiviral plasmids that interfere with miR-155-5p, followed by apoptosis analysis. Finally, miR-155-5p-targeted regulation of RAC1 expression was identified, as well as the interaction between RAC1 and CREB, the co-localization of RAC1 and CREB, and the binding of CREB to miR-15b. As measured, miR-155-5p was upregulated in the bone marrow of MDS patients. Further cell experiments validated that miR-155-5p promoted CD34+ cell apoptosis. miR-155-5p could reduce the transcriptional activity of miR-15b by inhibiting RAC1, dissociating the interaction between RAC1 and CREB, and inhibiting the activation of CREB. Upregulating RAC1, CREB, or miR-15b could reduce miR-155-5p-mediated apoptosis promotion on CD34+ cells. Additionally, miR-155-5p could force PD-L1 expression, and this effect was impaired by elevating RAC1, CREB, or miR-15b. In conclusion, miR-155-5p mediates PD-L1-mediated apoptosis of CD34+ cells in MDS by RAC1/CREB/miR-15b axis, thereby inhibiting bone marrow hematopoiesis.

19.
J Exp Clin Cancer Res ; 42(1): 160, 2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37415190

RESUMO

BACKGROUND: Endothelial-mesenchymal transition (EndoMT) is an emerging adaptive process that modulates lymphatic endothelial function to drive aberrant lymphatic vascularization in the tumour microenvironment (TME); however, the molecular determinants that govern the functional role of EndoMT remain unclear. Here, we show that cancer-associated fibroblast (CAF)-derived PAI-1 promoted the EndoMT of lymphatic endothelial cells (LECs) in cervical squamous cell carcinoma (CSCC). METHODS: Immunofluorescent staining of α-SMA, LYVE-1 and DAPI were examined in primary tumour samples obtained from 57 CSCC patients. Assessment of cytokines secreted by CAFs and normal fibroblasts (NFs) was performed using human cytokine antibody arrays. The phenotype of EndoMT in lymphatic endothelial cells (LECs), gene expression levels, protein secretion and activity of signaling pathways were measured by real-time RT-PCR, ELISA or western blotting. The function of lymphatic endothelial monolayers was examined by transwell, tube formation assay, transendothelial migration assay in vitro. Lymphatic metastasis was measured using popliteal lymph node metastasis model. Furthermore, association between PAI-1 expression and EndoMT in CSCC was analyzed by immunohistochemistry. The Cancer Genome Atlas (TCGA) databases was used to assess the association of PAI-1 with survival rate in CSCC. RESULTS: CAF-derived PAI-1 promoted the EndoMT of LECs in CSCC. LECs undergoing EndoMT could initiate tumour neolymphangiogenesis that facilitated cancer cell intravasation/extravasation, which in turn promoted lymphatic metastasis in CSCC. Mechanistically, PAI-1 activated the AKT/ERK1/2 pathways by directly interacting with low-density lipoprotein receptor-related protein (LRP1), thereby leading to elevated EndoMT activity in LECs. Blockade of PAI-1 or inhibition of LRP1/AKT/ERK1/2 abrogated EndoMT and consequently attenuated CAF-induced tumour neolymphangiogenesis. Furthermore, clinical data revealed that increased PAI-1 levels positively correlated with EndoMT activity and poor prognosis in CSCC patients. CONCLUSION: Our data indicate that CAF-derived PAI-1 acts as an important neolymphangiogenesis-initiating molecular during CSCC progression through modulating the EndoMT of LECs, resulting in promotion of metastasis ability in primary site. PAI-1 could serve as an effective prognostic biomarker and therapeutic target for CSCC metastasis.


Assuntos
Fibroblastos Associados a Câncer , Células Endoteliais , Feminino , Humanos , Movimento Celular/genética , Células Endoteliais/metabolismo , Metástase Linfática , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Microambiente Tumoral
20.
Front Mol Biosci ; 10: 1113061, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37325472

RESUMO

Transforming growth factor beta (TGFß) is named for the function it was originally discovered to perform-transformation of normal cells into aggressively growing malignant cells. It became apparent after more than 30 years of research, however, that TGFß is a multifaceted molecule with a myriad of different activities. TGFßs are widely expressed with almost every cell in the human body producing one or another TGFß family member and expressing its receptors. Importantly, specific effects of this growth factor family differ in different cell types and under different physiologic and pathologic conditions. One of the more important and critical TGFß activities is the regulation of cell fate, especially in the vasculature, that will be the focus of this review.

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