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1.
Brain Res ; : 149010, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38763503

RESUMEN

OBJECTIVE: Cerebral blood perfusion (CBP) reduction is a prevalent complication following subarachnoid hemorrhage (SAH) in clinical practice, often associated with long-term cognitive impairment and prognosis. Electroacupuncture (EA), a widely utilized traditional Chinese therapy for central nervous system disorders, has demonstrated promising therapeutic effects. This study aims to investigate the therapeutic potential of EA in restoring CBP in SAH rats and to explore the mechanisms involving HIF-1α in this process. METHODS: Rats were randomly assigned to one of five groups, including Sham, SAH, EA, EA + Saline, and EA + dimethyloxallyl glycine (DMOG) groups. EA treatment was administered for 10 min daily, while DMOG were intraperitoneally injected. Behavioral tests, cerebral blood flow monitoring, vascular thickness measurement, western blotting, and immunofluorescence staining were conducted to assess the therapeutic effects of EA on cerebral blood flow. RESULTS: SAH resulted in elevated levels of HIF-1α, endothelin (ET), ICAM-1, P-SELECTIN, E-SELECTIN, and decreased level of eNOS in the brain. This led to cerebral vasospasm, decreased CBF, and cognitive deficits in the rat SAH model. EA intervention downregulated the expression of HIF-1α, ET, ICAM-1, P-SELECTIN, and E-SELECTIN, while increasing eNOS expression. This alleviated cerebral vasospasm, restored CBF, and improved cognitive function. However, the administration of the HIF-1α stabilizer (DMOG) counteracted the therapeutic effects of EA. CONCLUSION: EA promotes the recovery of cerebral blood flow after SAH injury, attenuates cerebral vasospasm, and accelerates the recovery of cognitive dysfunction, and its mechanism of action may be related to the inhibition of the HIF-1α signaling pathway.

2.
Clin Transl Med ; 14(4): e1665, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38649789

RESUMEN

BACKGROUND: White matter injury (WMI) is an important pathological process after traumatic brain injury (TBI). The correlation between white matter functions and the myeloid cells expressing triggering receptor-2 (TREM2) has been convincingly demonstrated. Moreover, a recent study revealed that microglial sterol metabolism is crucial for early remyelination after demyelinating diseases. However, the potential roles of TREM2 expression and microglial sterol metabolism in WMI after TBI have not yet been explored. METHODS: Controlled cortical injury was induced in both wild-type (WT) and TREM2 depletion (TREM2 KO) mice to simulate clinical TBI. COG1410 was used to upregulate TREM2, while PLX5622 and GSK2033 were used to deplete microglia and inhibit the liver X receptor (LXR), respectively. Immunofluorescence, Luxol fast blue staining, magnetic resonance imaging, transmission electron microscopy, and oil red O staining were employed to assess WMI after TBI. Neurological behaviour tests and electrophysiological recordings were utilized to evaluate cognitive functions following TBI. Microglial cell sorting and transcriptomic sequencing were utilized to identify alterations in microglial sterol metabolism-related genes, while western blot was conducted to validate the findings. RESULTS: TREM2 expressed highest at 3 days post-TBI and was predominantly localized to microglial cells within the white matter. Depletion of TREM2 worsened aberrant neurological behaviours, and this phenomenon was mediated by the exacerbation of WMI, reduced renewal of oligodendrocytes, and impaired phagocytosis ability of microglia after TBI. Subsequently, the upregulation of TREM2 alleviated WMI, promoted oligodendrocyte regeneration, and ultimately facilitated the recovery of neurological behaviours after TBI. Finally, the expression of DHCR24 increased in TREM2 KO mice after TBI. Interestingly, TREM2 inhibited DHCR24 and upregulated members of the LXR pathway. Moreover, LXR inhibition could partially reverse the effects of TREM2 upregulation on electrophysiological activities. CONCLUSIONS: We demonstrate that TREM2 has the potential to alleviate WMI following TBI, possibly through the DHCR24/LXR pathway in microglia.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Glicoproteínas de Membrana , Microglía , Receptores Inmunológicos , Sustancia Blanca , Animales , Masculino , Ratones , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/genética , Modelos Animales de Enfermedad , Receptores X del Hígado/metabolismo , Receptores X del Hígado/genética , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Ratones Endogámicos C57BL , Ratones Noqueados , Microglía/metabolismo , Receptores Inmunológicos/metabolismo , Receptores Inmunológicos/genética , Sustancia Blanca/metabolismo , Sustancia Blanca/patología
3.
Transl Stroke Res ; 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38356020

RESUMEN

The inflammatory response following subarachnoid hemorrhage (SAH) may lead to Early Brain Injury and subsequently contribute to poor prognosis such as cognitive impairment in patients. Currently, there is a lack of effective strategies for SAH to ameliorate inflammation and improve cognitive impairment in clinical. This study aims to examine the inhibitory impact of remote ischemic post-conditioning (RIPostC) on the body's inflammatory response by regulating Th17/Treg cell homeostasis after SAH. The ultimate goal is to search for potential early treatment targets for SAH. The rat SAH models were made by intravascular puncture of the internal carotid artery. The intervention of RIPostC was administered for three consecutive days immediately after successful modeling. Behavioral experiments including the Morris water maze and Y-maze tests were conducted to assess cognitive functions such as spatial memory, working memory, and learning abilities 2 weeks after successful modeling. The ratio of Th17 cells and Treg cells in the blood was detected using flow cytometry. Immunofluorescence was used to observe the infiltration of neutrophils into the brain. Signal transducers and activators of transcription 5 (STAT5) and signal transducers and activators of transcription 3 (STAT3) phosphorylation levels, receptor-related orphan receptor gamma-t (RORγt), and forkhead box protein P3 (Foxp3) levels were detected by Western blot. The levels of anti-inflammatory factors (IL-2, IL-10, IL-5, etc.) and pro-inflammatory factors (IL-6, IL-17, IL-18, TNF-α, IL-14, etc.) in blood were detected using Luminex Liquid Suspension Chip Assay. RIPostC significantly improved the cognitive impairment caused by SAH in rats. The results showed that infiltration of Th17 cells and neutrophils into brain tissue increased after SAH, leading to the release of pro-inflammatory factors (IL-6, IL-17, IL-18, and TNF-α). This response can be inhibited by RIPostC. Additionally, RIPostC facilitates the transfer of Treg from blood to the brain and triggers the release of anti-inflammatory (IL-2, IL-10, and IL-5) factors to suppress the inflammation following SAH. Finally, it was found that RIPostC increased the phosphorylation of STAT5 while decreasing the phosphorylation of STAT3. RIPostC reduces inflammation after SAH by partially balancing Th17/Treg cell homeostasis, which may be related to downregulation of STAT3 and upregulation of STAT5 phosphorylation, which ultimately alleviates cognitive impairment in rats. Targeting Th17/Treg cell homeostasis may be a promising strategy for early SAH treatment.

5.
Metabolism ; 152: 155784, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38211696

RESUMEN

BACKGROUND AND AIM: Triglyceride (TG) levels are closely related to obesity, fatty liver and cardiovascular diseases, while the regulatory factors and mechanism for triglyceride homeostasis are still largely unknown. Zinc Finger Protein 638 (ZNF638) is a newly discovered member of zinc finger protein family for adipocyte function in vitro. The aim of the present work was to investigate the role of ZNF638 in regulating triglyceride metabolism in mice. METHODS: We generated ZNF638 adipose tissue specific knockout mice (ZNF638 FKO) by cross-breeding ZNF638 flox to Adiponectin-Cre mice and achieved adipose tissue ZNF638 overexpression via adenoviral mediated ZNF638 delivery in inguinal adipose tissue (iWAT) to examined the role and mechanisms of ZNF638 in fat biology and whole-body TG homeostasis. RESULTS: Although ZNF638 FKO mice showed similar body weights, body composition, glucose metabolism and serum parameters compared to wild-type mice under chow diet, serum TG levels in ZNF638 FKO mice were increased dramatically after refeeding compared to wild-type mice, accompanied with decreased endothelial lipoprotein lipase (LPL) activity and increased lipid absorption of the small intestine. Conversely, ZNF638 overexpression in iWAT reduced serum TG levels while enhanced LPL activity after refeeding in female C57BL/6J mice and obese ob/ob mice. Specifically, only female mice exhibited altered TG metabolism upon ZNF638 expression changes in fat. Mechanistically, RNA-sequencing analysis revealed that the TG regulator angiopoietin-like protein 8 (Angptl8) was highly expressed in iWAT of female ZNF638 FKO mice. Neutralizing circulating ANGPTL8 in female ZNF638 FKO mice abolished refeeding-induced TG elevation. Furthermore, we demonstrated that ZNF638 functions as a transcriptional repressor by recruiting HDAC1 for histone deacetylation and broad lipid metabolic gene suppression, including Angptl8 transcription inhibition. Moreover, we showed that the sexual dimorphism is possibly due to estrogen dependent regulation on ZNF638-ANGPTL8 axis. CONCLUSION: We revealed a role of ZNF638 in the regulation of triglyceride metabolism by affecting Angptl8 transcriptional level in adipose tissue with sexual dimorphism.


Asunto(s)
Tejido Adiposo , Proteína 8 Similar a la Angiopoyetina , Proteínas de Unión al ADN , Proteínas de Unión al ARN , Triglicéridos , Animales , Femenino , Ratones , Tejido Adiposo/metabolismo , Proteínas de Unión al ADN/metabolismo , Metabolismo de los Lípidos/genética , Ratones Endogámicos C57BL , Ratones Noqueados , Obesidad/genética , Obesidad/metabolismo , Proteínas de Unión al ARN/metabolismo , Factores de Transcripción/metabolismo , Triglicéridos/metabolismo , Dedos de Zinc
6.
J Pediatr Nurs ; 75: e1-e9, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38212174

RESUMEN

PURPOSE: Pediatric cancer is a significant health concern in China, and evaluating the impact of cancer and its treatment on the well-being of young patients is essential for both clinical care and research purposes. This study aimed to psychometrically validate the Patient-reported Outcomes Measurement Information System Pediatric-25 Profile (PROMIS-Pediatric-25) among Chinese children with cancer. DESIGN AND METHODS: We enrolled a group of 114 children living with cancer between the ages of 8 and 17. Each participant completed questionnaires that covered sociodemographic and clinical information and the PROMIS-Pediatric-25. The floor and ceiling effect was examined. Cronbach's alpha and split-half coefficient were examined to determine the reliability. Factor structure was explored by factor analysis. Three assumptions of Rasch model-based item response theory (IRT) were assessed. Differential item functioning (DIF) was investigated concerning factors of gender, diagnosis, and treatment stage. RESULTS: The floor or ceiling effects were detected for six domains. The reliability was found to be excellent. Furthermore, the factor structure of these six domains was validated. Our analysis confirmed that the assumptions required for IRT were met with acceptable unidimensionality, local independence, and good monotonicity. Additionally, we observed measurement equivalence, with outstanding levels of DIF across factors such as gender, diagnosis, and treatment stage. CONCLUSION: PROMIS-Pediatric 25 is a highly reliable and valid instrument for evaluating key domains of health-related quality of life in Chinese pediatric cancer patients. PRACTICE IMPLICATION: Nursing practice could engage the PROMIS-Pediatric 25 for accurate and quick children symptom and function assessment.


Asunto(s)
Neoplasias , Calidad de Vida , Humanos , Niño , Adolescente , Reproducibilidad de los Resultados , Psicometría , Encuestas y Cuestionarios , Neoplasias/diagnóstico , Neoplasias/terapia
7.
BMJ Open ; 13(11): e071288, 2023 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-37989373

RESUMEN

OBJECTIVES: Implementing ethics is crucial to prevent harm and promote widespread benefits in social experiments based on medical artificial intelligence (MAI). However, insufficient information is available concerning this within the paediatric healthcare sector. We aimed to conduct a comparative survey among paediatricians, nurses and health information technicians regarding ethics implementation knowledge of and attitude towards MAI social experiments at children's hospitals in Shanghai. DESIGN AND SETTING: A cross-sectional electronic questionnaire was administered from 1 July 2022 to 31 July 2022, at tertiary children's hospitals in Shanghai. PARTICIPANTS: All the eligible individuals were recruited. The inclusion criteria were as follows: (1) should be a paediatrician, nurse and health information technician, (2) should have been engaged in or currently participating in social experiments based on MAI, and (3) voluntary participation in the survey. PRIMARY OUTCOME: Ethics implementation knowledge of and attitude to MAI social experiments among paediatricians, nurses and health information technicians. RESULTS: There were 137 paediatricians, 135 nurses and 60 health information technicians who responded to the questionnaire at tertiary children's hospitals. 2.4-9.6% of participants were familiar with ethics implementation knowledge of MAI social experiments. 31.9-86.1% of participants held an 'agree' ethics implementation attitude. Health information technicians accounted for the highest proportion of the participants who were familiar with the knowledge of implementing ethics, and paediatricians or nurses accounted for the highest proportion among those who held 'agree' attitudes. CONCLUSIONS: There is a significant knowledge gap and variations in attitudes among paediatricians, nurses and health information technicians, which underscore the urgent need for individualised education and training programmes to enhance MAI ethics implementation in paediatric healthcare.


Asunto(s)
Inteligencia Artificial , Conocimientos, Actitudes y Práctica en Salud , Humanos , Niño , Estudios Transversales , China , Pediatras , Encuestas y Cuestionarios , Actitud del Personal de Salud , Hospitales
8.
Transl Stroke Res ; 2023 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-37935878

RESUMEN

Myelin sheath injury contributes to cognitive deficits following subarachnoid hemorrhage (SAH). G protein-coupled receptor 17 (GPR17), a membrane receptor, negatively regulates oligodendrocyte precursor cell (OPC) differentiation in both developmental and pathological contexts. Nonetheless, GPR17's role in modulating OPC differentiation, facilitating remyelination post SAH, and its interaction with downstream molecules remain elusive. In a rat SAH model induced by arterial puncture, OPCs expressing GPR17 proliferated prominently by day 14 post-onset, coinciding with compromised myelin sheath integrity and cognitive deficits. Selective Gpr17 knockdown in oligodendrocytes (OLs) via adeno-associated virus (AAV) administration revealed that reduced GPR17 levels promoted OPC differentiation, restored myelin sheath integrity, and improved cognitive deficits by day 14 post-SAH. Moreover, GPR17 knockdown attenuated the elevated expression of the inhibitor of DNA binding 2 (ID2) post-SAH, suggesting a GPR17-ID2 regulatory axis. Bi-directional modulation of ID2 expression in OLs using AAV unveiled that elevated ID2 counteracted the restorative effects of GPR17 knockdown. This resulted in hindered differentiation, exacerbated myelin sheath impairment, and worsened cognitive deficits. These findings highlight the pivotal roles of GPR17 and ID2 in governing OPC differentiation and axonal remyelination post-SAH. This study positions GPR17 as a potential therapeutic target for SAH intervention. The interplay between GPR17 and ID2 introduces a novel avenue for ameliorating cognitive deficits post-SAH.

9.
JMIR Form Res ; 7: e42202, 2023 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-37883175

RESUMEN

BACKGROUND: Medical artificial intelligence (AI) has significantly contributed to decision support for disease screening, diagnosis, and management. With the growing number of medical AI developments and applications, incorporating ethics is considered essential to avoiding harm and ensuring broad benefits in the lifecycle of medical AI. One of the premises for effectively implementing ethics in Medical AI research necessitates researchers' comprehensive knowledge, enthusiastic attitude, and practical experience. However, there is currently a lack of an available instrument to measure these aspects. OBJECTIVE: The aim of this study was to develop a comprehensive scale for measuring the knowledge, attitude, and practice of ethics implementation among medical AI researchers, and to evaluate its measurement properties. METHODS: The construct of the Knowledge-Attitude-Practice in Ethics Implementation (KAP-EI) scale was based on the Knowledge-Attitude-Practice (KAP) model, and the evaluation of its measurement properties was in compliance with the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) reporting guidelines for studies on measurement instruments. The study was conducted in 2 phases. The first phase involved scale development through a systematic literature review, qualitative interviews, and item analysis based on a cross-sectional survey. The second phase involved evaluation of structural validity and reliability through another cross-sectional study. RESULTS: The KAP-EI scale had 3 dimensions including knowledge (10 items), attitude (6 items), and practice (7 items). The Cronbach α for the whole scale reached .934. Confirmatory factor analysis showed that the goodness-of-fit indices of the scale were satisfactory (χ2/df ratio:=2.338, comparative fit index=0.949, Tucker Lewis index=0.941, root-mean-square error of approximation=0.064, and standardized root-mean-square residual=0.052). CONCLUSIONS: The results show that the scale has good reliability and structural validity; hence, it could be considered an effective instrument. This is the first instrument developed for this purpose.

10.
Int J Gynecol Pathol ; 2023 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-37732995

RESUMEN

Loss of estrogen receptor/progesterone receptor (ER/PR) in endometrial cancer (EC) is associated with tumor progression and poor outcomes. Elevated pretreatment cancer antigen 125 (CA 125) level is a risk factor for lymph node metastasis (LNM). We evaluated whether the combination of ER/PR expression and CA 125 level could be used as a biomarker to predict LNM. We retrospectively investigated patients with endometrioid EC who underwent complete staging surgery during January 2015 to December 2020. We analyzed ER/PR status using immunohistochemical staining, and quantified its expression using the sum of both ER/PR H-scores. Receiver operating characteristic curves were used to identify optimal cutoff values of H-score and CA 125 levels for predicting LNM. A nomogram for predicting LNM was constructed and validated by bootstrap resampling. In 396 patients, the optimal cutoff values of the ER/PR H-score and CA 125 were 407 (area under the receiver operating characteristic curve: 0.645, P=0.001) and 40 U/mL (area under the receiver operating characteristic curve: 0.762, P<0.001), respectively. Multivariate analysis showed that CA 125 ≥40 UmL (odds ratio: 10.02; 95% CI: 4.74-21.18) and ER/PR H-score <407 (odds ratio: 4.20; 95% CI: 1.55-11.32) were independent predictors. An LNM predictive nomogram was constructed using these 2 variables and our model yielded a negative predictive value and negative likelihood ratio of 98.3% and 0.14, respectively. ER/PR expression with pretreatment CA 125 levels can help estimate LNM risk and aid in decision-making regarding the need for lymphadenectomy in patients with endometrioid EC.

11.
Polymers (Basel) ; 15(17)2023 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-37688177

RESUMEN

Monodispersed polystyrene (PS) particles were prepared and deposited onto various kinds of textile fabrics using a gravity sedimentation method. The monodispersed PS particles were self-assembled on fabrics to form a photonic crystal, which has an iridescent structural color. The structural color of fabrics was determined by the bandgaps of photonic crystals. Moreover, the effect of the fabric substrate, including the raw materials, base color, and fabric weave, etc., on the structural color of the photonic crystals was studied. Scanning electron microscopy and UV-vis spectrometry were adopted to characterize the structure and optical performance of photonic crystals. The results indicate that the silk fabric with a black base color and satin weave contribute to a bright and pure textile structural color. In order to solve the problem of low color fastness of the structural color on the fabric surface, silk fibroin (SF) was introduced to the PS microsphere solution. Results show that the addition of SF slightly affects the brightness of the structural color, while it has a certain reinforcing effect on the structural color fastness to rubbing and washing.

12.
Polymers (Basel) ; 15(17)2023 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-37688195

RESUMEN

Reverse osmosis (RO) membrane materials play a key role in determining energy consumption. Currently, CTA is regarded as having one of the highest degrees of chlorine resistance among materials in the RO process. The hollow fiber membrane has the advantages of a large membrane surface area and a preparation process without any redundant processes. Herein, response surface methodology with Box-Behnken Design (BBD) was applied for optimizing the preparation conditions of the cellulose triacetate (CTA) hollow fiber RO membrane. There were four preparation parameters, including solid content, spinning temperature, post-treatment temperature, and post-treatment time, which could affect the permeability of the membrane significantly. In this study, the interaction between preparation parameters and permeability (permeate flux and salt rejection) was evaluated by regression equations. Regression equations can be applied to obtain the optimized preparation parameters of hollow fiber RO membranes and reasonably predict and optimize the permeability of the RO membranes. Finally, the optimized preparation conditions were solid content (44%), spinning temperature (167 °C), post-treatment temperature (79 °C), and post-treatment time (23 min), leading to a permeability of 12.029 (L·m-2·h-1) and salt rejection of 90.132%. This study of reinforced that CTA hollow fiber membrane may promote the transformation of the RO membrane industry.

13.
Brain Res Bull ; 202: 110743, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37591025

RESUMEN

Neuroinflammation and white matter microstructure damage are important causes of cognitive impairment after subarachnoid hemorrhage (SAH). Nod-like receptor protein 3 (NLRP3) plays an important role in neuroinflammation after SAH and may be a potential therapeutic target for treatment of white matter microstructure injury. In this study, we observed whether MCC950, a specific inhibitor of the NLRP3 inflammasome, exerted a therapeutic effect after SAH. The SAH model was induced by endovascular perforation in SpragueDawley rats. MCC950 was injected intraperitoneally 1 h after SAH at a dose of 10 mg/kg. The results showed that MCC950 significantly attenuated white matter microstructure damage in some brain regions, and behavioral experiments confirmed that MCC950 ameliorated cognitive function in rats after SAH, which may provide a new method for the treatment of cognitive dysfunction in SAH patients.


Asunto(s)
Lesiones Encefálicas , Hemorragia Subaracnoidea , Sustancia Blanca , Animales , Ratas , Lesiones Encefálicas/metabolismo , Cognición , Enfermedades Neuroinflamatorias , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/tratamiento farmacológico , Hemorragia Subaracnoidea/metabolismo , Sulfonamidas/farmacología , Sustancia Blanca/metabolismo
14.
Transl Oncol ; 37: 101756, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37595394

RESUMEN

Glioma is the most common tumor of the nervous system. The diffuse growth and proliferation of glioma poses great challenges for its treatment. Here, Transcriptomic analysis revealed that Rac GTPase activating protein 1 (RACGAP1) is highly expressed in glioma. RACGAP1 has been shown to play an important role in the malignant biological progression of a variety of tumors. However, the underlying role and mechanism in glioma remain poorly understood. By using quantitative real-time polymerase chain reaction (qRT-PCR), western blot, immunohistochemistry and Orthotopic mouse xenografts, we confirmed that knockdown of RACGAP1 impeded cell proliferation in glioma and prolonged the survival of orthotopic mice. Interestingly, we also found that inhibiting the expression of RACGAP1 reduced the expression of minichromosome maintenance 3 (MCM3) through RNA-seq and rescue assay, while Yin Yang 1 (YY1) transcriptionally regulated RACGAP1 expression. Furthermore, T7 peptide-decorated exosome (T7-exo) is regard as a promising delivery modality for targeted therapy of glioma, and the T7-siRACGAP1-exo significantly improved the survival time of glioma bearing mice. These results suggested that targeting RACGAP1 may be a potential strategy for glioma therapy.

15.
ACS Nano ; 17(17): 16432-16447, 2023 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-37646615

RESUMEN

Radiotherapy is a mainstay of glioblastoma (GBM) treatment; however, the development of therapeutic resistance has hampered the efficacy of radiotherapy, suggesting that additional treatment strategies are needed. Here, an in vivo loss-of-function genome-wide CRISPR screen was carried out in orthotopic tumors in mice subjected to radiation treatment to identify synthetic lethal genes associated with radiotherapy. Using functional screening and transcriptome analyses, glutathione synthetase (GSS) was found to be a potential regulator of radioresistance through ferroptosis. High GSS levels were closely related to poor prognosis and relapse in patients with glioma. Mechanistic studies demonstrated that GSS was associated with the suppression of radiotherapy-induced ferroptosis in glioma cells. The depletion of GSS resulted in the disruption of glutathione (GSH) synthesis, thereby causing the inactivation of GPX4 and iron accumulation, thus enhancing the induction of ferroptosis upon radiotherapy treatment. Moreover, to overcome the obstacles to broad therapeutic translation of CRISPR editing, we report a previously unidentified genome editing delivery system, in which Cas9 protein/sgRNA complex was loaded into Angiopep-2 (Ang) and the trans-activator of the transcription (TAT) peptide dual-modified extracellular vesicle (EV), which not only targeted the blood-brain barrier (BBB) and GBM but also permeated the BBB and penetrated the tumor. Our encapsulating EVs showed encouraging signs of GBM tissue targeting, which resulted in high GSS gene editing efficiency in GBM (up to 67.2%) with negligible off-target gene editing. These results demonstrate that a combination of unbiased genetic screens, and CRISPR-Cas9-based gene therapy is feasible for identifying potential synthetic lethal genes and, by extension, therapeutic targets.


Asunto(s)
Vesículas Extracelulares , Glioblastoma , Glioma , Animales , Ratones , Glioblastoma/genética , Glioblastoma/radioterapia , Sistemas CRISPR-Cas/genética , ARN Guía de Sistemas CRISPR-Cas , Vesículas Extracelulares/genética , Glutatión
16.
J Cancer Res Clin Oncol ; 149(13): 11807-11813, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37405474

RESUMEN

PURPOSE: To investigate whether the cost-effective, pretreatment tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen-125 (CA-125) can be used to predict lymph node metastasis (LNM) in endometrioid-type endometrial cancer (EC) and to develop a predictive model. METHODS: This was a single-center retrospective study of patients with endometrioid-type EC who underwent complete staging surgery between January 2015 and June 2022. We identified the optimal cut-off values of CEA and CA-125 for predicting LNM using receiver operating characteristic (ROC) curves. Stepwise multivariate logistic regression analysis was used to identify independent predictors. A nomogram for predicting LNM was constructed and validated by bootstrap resampling. RESULTS: The optimal cut-off values of CEA and CA-125 were 1.4 ng/mL (area under the ROC curve (AUC) 0.62) and 40 U/mL (AUC 0.75), respectively. Multivariate analysis showed that CEA (odds ratio (OR) 1.94; 95% confidence interval (CI) 1.01-3.74) and CA-125 (OR 8.75; 95% CI 4.42-17.31) were independent predictors of LNM. Our nomogram showed adequate discrimination with a concordance index of 0.78. Calibration curves for the probability of LNM showed optimal agreement between the predicted and actual probabilities. The risk of LNM for markers below the cut-offs was 3.6%. The negative predictive value and negative likelihood ratio were 96.6% and 0.26, respectively, with moderate ability to rule out the possibility of LNM. CONCLUSION: We report a cost-effective method of using pretreatment CEA and CA-125 levels to identify patients with endometrioid-type EC who are at a low risk for LNM, which may guide decision-making regarding aborting lymphadenectomy.


Asunto(s)
Carcinoma Endometrioide , Neoplasias Endometriales , Femenino , Humanos , Antígeno Carcinoembrionario , Estudios Retrospectivos , Antígeno Ca-125 , Metástasis Linfática/patología , Neoplasias Endometriales/cirugía , Neoplasias Endometriales/patología , Carcinoma Endometrioide/patología , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología
18.
Cancers (Basel) ; 15(7)2023 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-37046843

RESUMEN

Cancer-related fatigue (CRF) is the most common somatic discomfort in patients with gynecological cancers. CRF is often overlooked; however, it can impair the patients' quality of life considerably. This cross-sectional study aimed to identify the clinical characteristics of CRF in gynecological cancer patients. Questionnaires and the International Classification of Diseases 10th Revision (ICD-10) criteria were used to identify CRF. The enrolled patients were further categorized according to the amount of fatigue-related management received. Of the enrolled 190 patients, 40.0% had endometrial cancer, 28.9% had cervical cancer, and 31.1% had ovarian cancer. On the basis of the ICD-10 diagnostic criteria, 42.6% had non-cancer-related fatigue, 10% had CRF, and 51% had BFI-T questionnaire-based fatigue. Moreover, 77.9% of the study cohort had ever received fatigue-related management. Further analysis showed that patients with endometrial/cervical cancer, International Federation of Gynecology and Obstetrics stage >1, Eastern Cooperative Oncology Group performance status score ≥1, inadequate cancer treatment response, and receiving cancer treatment in the past week had a higher probability of receiving more fatigue-related management. The five-item predictive model developed from these factors may help physicians recognize patients seeking more fatigue-related management more efficiently. This is important as they may suffer from a more profound CRF.

19.
Nurs Open ; 10(7): 4196-4204, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36894867

RESUMEN

AIM: To revise the Supportive Care Needs Survey for Partners and Caregivers of Cancer Patients (SCNS-P&C) and evaluate the psychometric properties of the Chinese Version of the Supportive Care Needs Survey for Caregivers of Children with Paediatric Cancer (SCNS-C-Ped-C) in caregivers of children with paediatric cancer. DESIGN: A cross sectional design was used. METHODS: In this methodological research, the reliability and validity of the SCNS-C-Ped-C were measured by a questionnaire survey among 336 caregivers of children with paediatric cancer in China. The construct validity was evaluated by exploratory factor analysis and internal consistency was examined by Cronbach's alpha, split-half reliability, and corrected item-to-total correlation coefficients. RESULTS: The exploratory factor analysis revealed six factors consist of: Healthcare and Informational Needs, Daily Care and Communication Needs, Psychological and Spiritual Needs, Medical Service Needs, Economic Needs, and Emotional Needs, explaining 65.615% of the variance. The Cronbach's alpha was 0.968 at full scale and 0.603-0.952 on the six domains. The split-half reliability coefficient was 0.883 at full scale and 0.659-0.931 on the six domains. CONCLUSIONS: The SCNS-C-Ped-C demonstrated both reliability and validity. It can be used to evaluate multi-dimensional supportive care needs for caregivers of children with paediatric cancer in China.


Asunto(s)
Cuidadores , Neoplasias , Humanos , Niño , Psicometría/métodos , Cuidadores/psicología , Reproducibilidad de los Resultados , Estudios Transversales , Evaluación de Necesidades , Neoplasias/terapia
20.
Transl Pediatr ; 12(2): 113-124, 2023 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-36891361

RESUMEN

Background: Characterized by rapid transmission but lower severity, the new Omicron wave brought about an acute increase in local corona virus disease 2019 (COVID-19) cases in Shanghai, followed by stricter infection prevention and control strategies. Inevitably, more time was required for emergency consultation and treatment of children with critical illnesses. Therefore, a multidimensional approach was designed to streamline the emergency service and reduce the incidence of nosocomial infection of sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the Omicron wave for the emergency department (ED) at the Children's Hospital of Fudan University (CHFU). Methods: A multidimensional approach was implemented in the ED to help achieve a balance between the demand for emergency services and pandemic control, consisting of ED layout adjustment; electronic screening (E-screening) measures; standard management processes for patients, medical staff, and goods transfer; reliable disinfection measures; and a surveillance system for infection prevention and control. To evaluate the effect of the management strategy, the data on nosocomial infection cases and occupational exposure episodes among staff in the ED were collected. The demographic and clinical characteristics of level I/II children by the five-level pediatric triage tool and their mean duration of stay in the resuscitation room were collected. Results: There were 12,114 ED visitors from March 1 to May 31 in 2022, among which 53.24% were medical emergencies (6,449/12,114) and 46.76% were surgical emergencies (5,665/12,114). Twenty-nine patients were sent to the buffer zone, four of whom were transferred to the pediatric intensive care unit (PICU) because of the critical situation. Six patients tested positive for COVID-19 after entering ED, including three in the buffer zone and three in the ED clinic, causing a temporary closure of the ED for disinfection. There were no reports on medical care delays, unintended deaths, staff with COVID-19 infection, or occupational exposures to COVID-19. Conclusions: Our findings highlight the effectiveness of the multidimensional approach, which can simultaneously meet the emergency care needs of patients as well as pandemic prevention and control. However, the results were obtained against the proportional decrease in clinic visitors due to the Shanghai lockdown. Dynamic assessment and further optimization may be adopted to cope with the pre-pandemic visit volume.

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