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1.
Indian J Hematol Blood Transfus ; 40(4): 668-675, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39469165

RESUMEN

Central line-associated bloodstream infections (CLABSIs) can result in worse outcomes and high hospitalization cost for patients. This study aimed to assess the effectiveness of multi-department cooperation, intelligent prevention, and supervision (MDCIPS) in reducing the incidence of CLABSIs and improving the clinical outcomes of the patients. Key issues were identified through a literature review and survey on the status quo. A MDCIPS model was thus built. A total of 440 patients with indwelling central venous catheters (CVCs) were enrolled in the study. The control group (n = 219) received conventional infection-control managements, while the intervention group (n = 221) received MDCIPS interventions in addition to conventional infection-control managements. The number of CLABSIs patients, incidence of CLABSIs, average length of hospital stay, average total hospitalization cost, and disease outcomes were compared between the two groups. The intervention group had a significant reduction in the number and incidence of CLABSIs (0[0%] vs. 4[1.33%], P < 0.05). Two of the four patients with CLABSIs in the control group died. The average length of hospital stay was significantly longer in the control group than the intervention group (17 days vs. 13 days, P < 0.001). The average hospitalization cost in the control group was much higher than that in the intervention group (92.8 thousand yuan vs. 65.2 thousand yuan, P < 0.001). Patient outcome was improved in the intervention group than the control group (P = 0.001). In summary, the MDCIPS model effectively reduces the incidence of CLABSIs, alleviates the patients' economic burden, and improves the clinical outcomes of the patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-024-01760-8.

4.
IEEE Trans Med Imaging ; PP2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39331543

RESUMEN

Medical image segmentation is a fundamental task for medical image analysis and surgical planning. In recent years, UNet-based networks have prevailed in the field of medical image segmentation. However, convolutional neural networks (CNNs) suffer from limited receptive fields, which fail to model the long-range dependency of organs or tumors. Besides, these models are heavily dependent on the training of the final segmentation head. And existing methods can not well address aforementioned limitations simultaneously. Hence, in our work, we proposed a novel shape prior module (SPM), which can explicitly introduce shape priors to promote the segmentation performance of UNet-based models. The explicit shape priors consist of global and local shape priors. The former with coarse shape representations provides networks with capabilities to model global contexts. The latter with finer shape information serves as additional guidance to relieve the heavy dependence on the learnable prototype in the segmentation head. To evaluate the effectiveness of SPM, we conduct experiments on three challenging public datasets. And our proposed model achieves state-of-the-art performance. Furthermore, SPM can serve as a plug-and-play structure into classic CNNs and Transformer-based backbones, facilitating the segmentation task on different datasets. Source codes are available at https://github. com/AlexYouXin/Explicit-Shape-Priors.

5.
Cancer Cell Int ; 24(1): 276, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39103836

RESUMEN

BACKGROUND: Cancer stem cells (CSCs) are critical factors that limit the effectiveness of gastric cancer (GC) therapy. Circular RNAs (circRNAs) are confirmed as important regulators of many cancers. However, their role in regulating CSC-like properties of GC remains largely unknown. Our study aimed to investigate the role of circUBA2 in CSC maintenance and the underlying mechanisms. METHODS: We identified circUBA2 as an upregulated gene using circRNA microarray analysis. qRT-PCR was used to examine the circUBA2 levels in normal and GC tissues. In vitro and in vivo functional assays were performed to validate the role of circUBA2 in proliferation, migration, metastasis and CSC-like properties of GC cell. The relationship between circUBA2, miR-144-5p and STC1 was characterised using bioinformatics analysis, a dual fluorescence reporter system, FISH, and RIP assays. RESULTS: CircUBA2 expression was significantly increased in GC tissues, and patients with GC with high circUBA2 expression had a poor prognosis. CircUBA2 enhances CSC-like properties of GC, thereby promoting cell proliferation, migration, and metastasis. Mechanistically, circUBA2 promoted GC malignancy and CSC-like properties by acting as a sponge for miR-144-5p to upregulate STC1 expression and further activate the IL-6/JAK2/STAT3 signaling pathway. More importantly, the ability of circUBA2 to enhance CSC-like properties was inhibited by tocilizumab, a humanised Interleukin-6 receptor (IL-6R) antibody. Thus, circUBA2 knockdown and tocilizumab synergistically inhibited CSC-like properties. CONCLUSIONS: Our study demonstrated the critical role of circUBA2 in regulating CSC-like properties in GC. CircUBA2 may be a promising prognostic biomarker for GC.

6.
J Org Chem ; 89(17): 12170-12175, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39155458

RESUMEN

N,N-Dimethylformamide was reacted with hexamethyldisilazane to generate an N,N-dimethylformimidamide intermediate; thereafter, a reaction with acetophenones/ß-diketones was induced to form enaminones. The one-pot synthetic protocol described in this paper can be applied to synthesize 1,4-disubstituted 1,2,3-triazoles and 1,4,5-trisubstituted 1,2,3-triazoles, in which organic azides are used as substrates under optimized conditions. Furthermore, this protocol uses readily available materials, is nearly free of solvent, can be applied to gram-scale operations, and leads to the formation of structurally diverse products with favorable yields.

7.
J Immunother Cancer ; 12(8)2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39209451

RESUMEN

BACKGROUND: The interleukin (IL)-1-family receptor antagonist IL-38 has emerged as a negative regulator of auto-inflammation. Given the intricate interplay between antitumor immunity and auto-inflammation, we hypothesized that blocking IL-38 may enhance tumor immune control. METHODS: Our hypothesis was tested in the transgenic polyoma virus middle T oncoprotein mammary carcinoma model that is suitable for identifying strong immunomodulators. To investigate the effect of acute IL-38 blockade, we used a neutralizing antibody, alone or in combination with chemotherapy. Immune cell composition and location in tumors were determined by flow cytometry and immunohistochemistry, respectively. The role of γδ T cells was studied using an antibody blocking γδ T-cell receptor signaling. Whole transcriptome RNA sequencing and RNA expression analysis were employed to determine mechanisms downstream of IL-38 neutralization. Additionally, in vitro assays with γδ T cells, CD8+ T cells and cDC1, followed by in vivo CD8+ T cell depletion, were performed to study the underlying mechanistic pathways. RESULTS: Both, genetic ablation of IL-38 and neutralization with the antibody, reduced tumorigenesis, and IL-38 blockade improved chemotherapy efficacy. This was accompanied by an augmented lymphocyte infiltrate dominated by γδ T cells and CD8+ T cells, and signaling through the γδ-T-cell receptor was required for CD8+ T cell infiltration. Rather than directly interacting with CD8+ T cells, γδ T cells recruited conventional dendritic cells (cDC1) into tumors via the chemokine Xcl1. cDC1 in turn activated CD8+ T cells via the Notch pathway. Moreover, IL-38 negatively correlated with cDC1, XCL1-producing γδ T cells, T-cell infiltrates and survival in patients with mammary carcinoma. CONCLUSIONS: These data suggest that interfering with IL-38 improves antitumor immunity even in immunologically cold tumors.


Asunto(s)
Anticuerpos Neutralizantes , Animales , Femenino , Humanos , Ratones , Anticuerpos Neutralizantes/farmacología , Anticuerpos Neutralizantes/inmunología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Línea Celular Tumoral , Interleucina-1/metabolismo , Interleucina-1/antagonistas & inhibidores , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo
9.
Hum Vaccin Immunother ; 20(1): 2387461, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-39149877

RESUMEN

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory tissue disease. In view of the explosive growth in research on SLE, bibliometrics was performed to evaluate the 100 top-cited papers in this realm. We performed the search with terms "systemic lupus erythematosus" the Web of Science Core Collection database on May 3, 2023. Relevant literatures were screened. Data were extracted and analyzed by SPSS. The citations of 100 top-cited SLE studies spanned from 472 to 13,557. Most studies (60 out of 100) were conducted in the United States. Total citation times were positively associated with ACY, which was negatively correlated with the length of time since publication. Approximately half of the studies focused on the underlying mechanisms of SLE. New biologic therapies garnered attention and development. Our findings provide valuable insights into the developments in crucial areas of SLE and shed contributions to future studies.


Asunto(s)
Bibliometría , Lupus Eritematoso Sistémico , Humanos
10.
Nat Commun ; 15(1): 7201, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39169020

RESUMEN

Photosynthesis converting solar energy to chemical energy is one of the most important chemical reactions on earth. In cyanobacteria, light energy is captured by antenna system phycobilisomes (PBSs) and transferred to photosynthetic reaction centers of photosystem II (PSII) and photosystem I (PSI). While most of the protein complexes involved in photosynthesis have been characterized by in vitro structural analyses, how these protein complexes function together in vivo is not well understood. Here we implemented STAgSPA, an in situ structural analysis strategy, to solve the native structure of PBS-PSII supercomplex from the cyanobacteria Arthrospira sp. FACHB439 at resolution of ~3.5 Å. The structure reveals coupling details among adjacent PBSs and PSII dimers, and the collaborative energy transfer mechanism mediated by multiple super-PBS in cyanobacteria. Our results provide insights into the diversity of photosynthesis-related systems between prokaryotic cyanobacteria and eukaryotic red algae but are also a methodological demonstration for high-resolution structural analysis in cellular or tissue samples.


Asunto(s)
Cianobacterias , Complejo de Proteína del Fotosistema II , Ficobilisomas , Ficobilisomas/metabolismo , Ficobilisomas/química , Complejo de Proteína del Fotosistema II/metabolismo , Complejo de Proteína del Fotosistema II/química , Cianobacterias/metabolismo , Fotosíntesis , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Complejo de Proteína del Fotosistema I/metabolismo , Complejo de Proteína del Fotosistema I/química , Transferencia de Energía , Modelos Moleculares , Microscopía por Crioelectrón
11.
BMC Emerg Med ; 24(1): 113, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38982343

RESUMEN

OBJECTIVES: The purpose of this study was to investigate the preferred modes of transportation to the hospital among patients with acute stroke and acute myocardial infarction (AMI), as well as to identify the factors that influence the utilization of ambulances. METHODS: We conducted a cross-sectional study, including patients who were diagnosed with acute stroke and AMI, at the people's hospital of Zhongjiang, from September 30th, 2022 to August 30th, 2023. All patients were divided into emergency medical service (EMS)-activation group and self-transportation group. Chi-square and t-tests were utilized to discern differences between groups at baseline. To screen relevant variables, we employed the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis using R package glmnet. Subsequently, we performed a logistic regression analysis to identify predictors of EMS activation according the results of LASSO regression. RESULTS: we collected 929 valid questionnaires. 26.16% of the patients required the services of EMS. 90.9% of individuals have not received any formal first aid education. 42.1% of them reported that they had no understanding of cardiovascular and cerebrovascular diseases. Diagnosed as AMI (OR 0.22, 95%CI 0.06 to 0.88) or acute cerebral infarction (OR 0.26, 0.10 to 0.68), the distance between the patient and the nearest 120 network hospital when the patient had these symptoms (OR 0.97, 0.94 to 0.99), the patient's son or daughter was there when the patient was symptomatic (OR 0.58, 0.37 to 0.94), the patient (OR 0.19, 0.05 to 0.72) and the patient's partner (wife or husband) (OR 0.36, 0.16 to 0.85) had decided that the patient needed further medical help, Among patients who did not seek immediate help after symptom onset, thinking that the symptoms will disappear spontaneously (OR 0.34, 0.13 to 0.92) or not wanting to disturb others (OR 0.06, 0.01 to 0.66) or believing that they are not important symptoms (OR 0.15, 0.05 to 0.42) were factors independently associated with less ambulance use. Age (OR 1.02, 1.00 to 1.04), Stroke patients have experienced symptoms of disturbance of consciousness or convulsions (OR 2.99, 1.72 to 5.2) were independent factors associated with increased ambulance use. CONCLUSION: There is still ambulance underutilization among patients with acute stroke and AMI in county territory of China. Moreover, it is needed to raise the level of first aid education and awareness about EMS. Additionally, private clinic doctors and the public should gain adequate understanding of the severity of acute stroke and AMI, as well as their common symptoms, the crucial importance of prompt medical intervention. Finally, we propose that all township hospitals should be integrated into the 120 emergency networks and equipped with emergency first aid capabilities, pre-hospital care, and transportation abilities.


Asunto(s)
Servicios Médicos de Urgencia , Infarto del Miocardio , Accidente Cerebrovascular , Humanos , Estudios Transversales , Masculino , Femenino , China , Infarto del Miocardio/terapia , Persona de Mediana Edad , Accidente Cerebrovascular/terapia , Anciano , Servicios Médicos de Urgencia/estadística & datos numéricos , Transporte de Pacientes/estadística & datos numéricos , Encuestas y Cuestionarios , Ambulancias/estadística & datos numéricos
12.
J Dig Dis ; 25(6): 380-393, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38992957

RESUMEN

OBJECTIVES: To evaluate physicians' awareness and knowledge towards pediatric nonalcoholic fatty liver disease (NAFLD) and their attitude toward change in nomenclature from NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) in China. METHODS: The questionnaire survey contained five parts (characteristics of the participants, epidemiology, diagnosis, management of NAFLD, and attitudes toward the nomenclature of MAFLD/MASLD). The participants included 53 hepatologists, 88 gastroenterologists (GEs), 74 endocrinologists (ENDOs), 61 primary care physicians (PCPs), and 157 pediatricians across 31 municipalities, provinces and autonomous regions of China's mainland. RESULTS: Hepatologists saw the largest number of pediatric NAFLD patients annually (median 9 [range 1-20]), with the lowest number by PCPs (even notwithstanding one patient annually). The primary sources of pediatric NAFLD knowledge were acquired via guidelines. Hepatologists had the highest total knowledge score among all five types of physicians. Approximately one-third of nonspecialists (ENDOs and PCPs) considered liver biopsy necessary for pediatric NAFLD patients, and this percentage increased to half in specialists (hepatologists and GEs). For nonspecialists, the major barriers to the management of pediatric NAFLD were poor patient adherence to lifestyle modifications and lacking confidence in managing NAFLD. Above 90% physicians agreed to change the nomenclature NAFLD to MAFLD; however, they were not sure whether it could reduce the economic burden. CONCLUSIONS: Despite the epidemic of pediatric NAFLD in China, a significant knowledge gap remains in the identification, diagnosis, and treatment of pediatric NAFLD, particularly among frontline workers such as pediatricians and PCPs. More education programs should be carried out in the future.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/terapia , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , China/epidemiología , Niño , Masculino , Femenino , Encuestas y Cuestionarios , Adulto , Pautas de la Práctica en Medicina/estadística & datos numéricos , Actitud del Personal de Salud , Competencia Clínica , Persona de Mediana Edad , Médicos de Atención Primaria , Pediatras/estadística & datos numéricos , Médicos
14.
Front Pharmacol ; 15: 1415310, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39035994

RESUMEN

Introduction: This study aimed to investigate the role of Nicotinamide N-methyltransferase (NNMT) in the drug sensitivity of non-small cell lung cancer (NSCLC) cells, with a focus on its impact on autophagy and resistance to the chemotherapeutic agent osimertinib. The study hypothesized that NNMT knockdown would enhance drug sensitivity by modifying autophagic processes, providing a potential new therapeutic target for overcoming chemoresistance in lung cancer. Methods: Proteomic analysis was utilized to identify changes in protein expression following NNMT knockdown in H1975 and H1975 osimertinib resistance (H1975OR) lung cancer cell lines. Gene expression patterns and their correlation with NNMT expression in lung cancer patients were analyzed using The Cancer Genome Atlas (TCGA) dataset. Additionally, a predictive model for lung cancer survival was developed via lasso regression analysis based on NNMT-associated gene expression. Drug sensitivity was assessed using the IC50 values and apoptosis ratio, and autophagy was evaluated through Western blot and flow cytometric analysis. Results: Significant variations in the expression of 1,182 proteins were observed following NNMT knockdown, with a significant association with autophagy-related genes. Analysis of gene expression patterns unveiled a significant correlation between NNMT expression and specific changes in gene expression in lung cancer. The predictive model successfully forecasted lung cancer patient survival outcomes, highlighting the potential of NNMT-associated genes in predicting patient survival. Knockdown of NNMT reversed osimertinib resistance in H1975 cells, as evidenced by altered IC50 values and apoptosis ratio, and changes were observed in autophagy markers. Discussion: Knockdown of NNMT in lung cancer cells enhances drug sensitivity by modulating autophagy, providing a promising therapeutic target to overcome chemoresistance in NSCLC. The study underscores the importance of NNMT in lung cancer pathology and underscores its potential as a predictive marker for clinical outcomes. Additionally, the developed predictive model further supports the clinical relevance of NNMT-associated gene expression in improving the prognosis of lung cancer patients.

15.
Biomed Mater ; 19(5)2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39059433

RESUMEN

To explore the feasibility and safety of biomaterials for posterior scleral reinforcement (PSR) in rabbits. Decellularization and genipin crosslink were applied to the fresh bovine pericardium and porcine endocranium, and then mechanical properties, suture retention strength, and stability were tested. PSR operation was performed on 24 rabbit eyes using treated biological materials. Ophthalmic examination was performed regularly before and after PSR operation (1 week, 1 month, 3 months, 6 months). To evaluate the effectiveness, A ultrasound, diopter, and optical coherence tomography were conducted. General condition, fundus photograph, and pathological examination were recorded to evaluate the safety. Compared with genipin crosslinked bovine pericardium (Gen-BP) (21.29 ± 13.29 Mpa), genipin crosslinked porcine endocranium (Gen-PE) (34.85 ± 3.67 Mpa,P< 0.01) showed a closer elastic modulus to that of genipin crosslinked human sclera. There were no complications or toxic reactions directly related to the materials. Capillary hyperplasia, inflammatory cell infiltration, and collagen fiber deposition were observed, and the content of type I collagen fibers increased after PSR. Overall, the choroidal thickness of treated eyes was significantly thickened at different time points after PSR, which were 96.84 ± 21.08 µm, 96.72 ± 22.00 µm, 90.90 ± 16.57 µm, 97.28 ± 14.74 µm, respectively. The Gen-PE group showed changes that were almost consistent with the overall data. Gen-BP and Gen-PE are safe biological materials for PSR. The Gen-PE group demonstrated more significant advantages over the Gen-BP group in terms of material properties.


Asunto(s)
Materiales Biocompatibles , Estudios de Factibilidad , Iridoides , Ensayo de Materiales , Esclerótica , Animales , Conejos , Materiales Biocompatibles/química , Bovinos , Porcinos , Iridoides/química , Suturas , Pericardio , Tomografía de Coherencia Óptica , Humanos , Reactivos de Enlaces Cruzados/química , Módulo de Elasticidad
16.
Tissue Eng Part A ; 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38832873

RESUMEN

Xenotransplantation of acellular adipose matrix (AAM) has come to prominence as an intriguing option for soft tissue reconstruction. However, the presence of immunogenic antigens within AAM can trigger unfavorable immune reactions, leading to inadequate in vivo regeneration outcomes. Therefore, the development of advanced technology capable of modulating immune responses is crucial for the therapeutic implementation of AAM xenografts. In this work, an innovative technique is created to bypass the immune system by covering the surface of both AAM and Arg-Gly-Asp (RGD) peptide-modified AAM xenografts with autologous red blood cell (RBC) membrane. The RBC membrane coating remained persistent and exhibited no significant decline even after 21 days. Moreover, it effectively reduced the expression of antigen major histocompatibility complex class 1 (MHC1) on the AAM surface. Following xenogeneic transplantation, the RBC-coated xenografts demonstrated increased expression of the adipogenic factor PPAR-γ, Adipoq, Fabp4, Fasn, and Plin1 and higher numbers of adipocytes. In addition, they exhibited decreased expression of immunological factors, including IL-6, IL-2, IFN-γ, and TNF-α, and fewer inflammatory cells. These findings indicate that RBC membrane coating successfully suppressed immune responses and promoted increased adipogenesis in AAM xenografts. Therefore, AAM camouflage coating with RBC has a lot of potential as a biomaterial for soft tissue reconstruction in clinical settings.

17.
Front Endocrinol (Lausanne) ; 15: 1361447, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38812818

RESUMEN

Background: Childhood obesity tends to persist into adulthood, predisposing individuals to cardiometabolic risk (CMR). This study aims to investigate the mediating role of cardiorespiratory fitness (CRF) in the associations between multiple fatness indicators and individual CMR markers and clustered CMR-score, and explore sex differences. Methods: We recruited 1,557 children (age: 8 to 10, male/female: 52.7%/47.3%) in September 2022 in Ningbo, China. Physical examinations, overnight fasting blood test, and CRF was evaluated. The CMR-score was calculated by summing age- and sex-specific z scores of four CMR markers, including mean arterial blood pressure, triglycerides, the total cholesterol to high-density lipoprotein cholesterol ratio, and homeostatic model assessment for insulin resistance. Generalized linear mixed models were used to identify the associations, mediation analyses were performed to dissect the function of CRF. Results: Partial correlation analyses revealed positive associations between high fatness indicators (including body mass index [BMI], BMI z score, body fat mass index [BFMI] and waist-to-height ratio [WHtR]) and increased CMR markers, whereas high CRF was associated with decreased CMR markers (all P < 0.05). In the mediation analyses, CRF emerged as a partial mediator, attenuating the relationship between four fatness indicators and CMR-score. Specifically, CRF mediated 6.5%, 7.7%, 5.3%, and 12.5% of the association between BMI, BMI z score, BFMI, WHtR and CMR-score (all P < 0.001). And the mediating effects of CRF between WHtR and four individual CMR markers was particularly robust, ranging from 10.4% to 21.1% (all P < 0.05). What's more, CRF mediates the associations between WHtR and CMR-score more pronounced in girls than boys with a mediation effect size of 17.3% (P < 0.001). Conclusion: In Chinese children, CRF partially mitigates the adverse effects of fatness on CMR, underscoring the significance of enhancing CRF in children.


Asunto(s)
Índice de Masa Corporal , Factores de Riesgo Cardiometabólico , Capacidad Cardiovascular , Humanos , Masculino , Femenino , Niño , Capacidad Cardiovascular/fisiología , China/epidemiología , Adiposidad/fisiología , Obesidad Infantil/epidemiología , Obesidad Infantil/fisiopatología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Estudios Transversales , Pueblos del Este de Asia
18.
Aesthetic Plast Surg ; 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38777930

RESUMEN

BACKGROUND: In plastic surgery tissue transplantation, tissue ischemia limits transplanted tissue survival. Adipose-derived stem cells (ASCs) and stromal vascular fraction (SVF) show potential for promoting angiogenesis and rescuing ischemic conditions. However, when SVF and ASC suspensions are utilized without the protection of extracellular matrix, the retention rate of transplanted cells tends to be diminished, leading to an unsatisfactory therapeutic outcome. To overcome this, adipose tissue-derived microvascular fragments (ad-MVFs) have emerged as a promising solution. METHODS: We conducted enzymatic digestion on human adipose tissue to generate ad-MVFs. These fragments underwent a thorough characterization process, utilizing electron microscopy to assess their structural attributes and enabling a detailed analysis of their intricate morphology. Furthermore, our team investigated the cellular composition of these microvascular fragments, subsequently confirming their ability to enhance the viability of ischemic skin flaps. RESULTS: The resulting product primarily comprised fragments with sizes ranging from 20 to 50 µm, and some exhibited a sophisticated network-like structure. Electron microscopy examination revealed the presence of collagen components in the product. Additionally, flow cytometry analysis indicated a substantial abundance of adipose-derived stem cells and endothelial cells within these microvascular fragments. Significantly, when tested in treating an ischemic skin flap in a nude mouse model, the product exhibited superior therapeutic efficacy compared to SVF cell suspension. CONCLUSION: We have successfully generated human ad-MVFs and established standardized procedures. Compared with SVF, Ad-MVFs have a better effect in the treatment of ischemic diseases. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

19.
Theranostics ; 14(7): 2915-2933, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38773976

RESUMEN

Background: Pyroptosis plays a crucial role in immune responses. However, the effects of pyroptosis on tumor microenvironment remodeling and immunotherapy in gastric cancer (GC) remain unclear. Patients and Methods: Large-sample GEO data (GSE15459, GSE54129, and GSE62254) were used to explore the immunoregulatory roles of pyroptosis. TCGA cohort was used to elucidate multiple molecular events associated with pyroptosis, and a pyroptosis risk score (PRS) was constructed. The prognostic performance of the PRS was validated using postoperative GC samples from three public databases (n=925) and four independent Chinese medical cohorts (n=978). Single-cell sequencing and multiplex immunofluorescence were used to elucidate the immune cell infiltration landscape associated with PRS. Patients with GC who received neoadjuvant immunotherapy (n=48) and those with GC who received neoadjuvant chemotherapy (n=49) were enrolled to explore the value of PRS in neoadjuvant immunotherapy. Results: GC pyroptosis participates in immune activation in the tumor microenvironment and plays a powerful role in immune regulation. PRS, composed of four pyroptosis-related differentially expressed genes (BATF2, PTPRJ, RGS1, and VCAN), is a reliable and independent biomarker for GC. PRSlow is associated with an activated pyroptosis pathway and greater infiltration of anti-tumor immune cells, including more effector and CD4+ T cells, and with the polarization of tumor-associated macrophages in the tumor center. Importantly, PRSlow marks the effectiveness of neoadjuvant immunotherapy and enables screening of GC patients with combined positive score ≥1 who benefit from neoadjuvant immunotherapy. Conclusion: Our study demonstrated that pyroptosis activates immune processes in the tumor microenvironment. A low PRS correlates with enhanced infiltration of anti-tumor immune cells at the tumor site, increased pyroptotic activity, and improved patient outcomes. The constructed PRS can be used as an effective quantitative tool for pyroptosis analysis to guide more effective immunotherapeutic strategies for patients with GC.


Asunto(s)
Inmunoterapia , Terapia Neoadyuvante , Piroptosis , Neoplasias Gástricas , Microambiente Tumoral , Humanos , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/terapia , Neoplasias Gástricas/patología , Terapia Neoadyuvante/métodos , Microambiente Tumoral/inmunología , Inmunoterapia/métodos , Masculino , Pronóstico , Femenino , Biomarcadores de Tumor/metabolismo , Persona de Mediana Edad , Regulación Neoplásica de la Expresión Génica , Multiómica
20.
Adv Mater ; 36(27): e2402379, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38655900

RESUMEN

Circulating tumor cells (CTCs) detection presents significant advantages in diagnosing liver cancer due to its noninvasiveness, real-time monitoring, and dynamic tracking. However, the clinical application of CTCs-based diagnosis is largely limited by the challenges of capturing low-abundance CTCs within a complex blood environment while ensuring them alive. Here, an ultrastrong ligand, l-histidine-l-histidine (HH), specifically targeting sialylated glycans on the surface of CTCs, is designed. Furthermore, HH is integrated into a cell-imprinted polymer, constructing a hydrogel with precise CTCs imprinting, high elasticity, satisfactory blood compatibility, and robust anti-interference capacities. These features endow the hydrogel with excellent capture efficiency (>95%) for CTCs in peripheral blood, as well as the ability to release CTCs controllably and alive. Clinical tests substantiate the accurate differentiation between liver cancer, cirrhosis, and healthy groups using this method. The remarkable diagnostic accuracy (94%), lossless release of CTCs, material reversibility, and cost-effectiveness ($6.68 per sample) make the HH-based hydrogel a potentially revolutionary technology for liver cancer diagnosis and single-cell analysis.


Asunto(s)
Histidina , Hidrogeles , Neoplasias Hepáticas , Células Neoplásicas Circulantes , Hidrogeles/química , Humanos , Histidina/química , Células Neoplásicas Circulantes/patología , Células Neoplásicas Circulantes/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/diagnóstico , Línea Celular Tumoral , Separación Celular/métodos , Polímeros/química , Impresión Molecular/métodos
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