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1.
Mol Biol Rep ; 51(1): 762, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874690

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is experiencing a concerning rise in both incidence and mortality rates. Current therapeutic strategies are limited in their effectiveness, largely due to the complex causes of the disease and significant levels of drug resistance. Given the latest developments in human umbilical cord mesenchymal stem cells (hUC-MSCs) research, there is a debate over the continued use of stem cell transplantation for treating tumors. Consequently, this study seeks to explore the role of hUC-MSCs in the management of HCC. METHODS AND RESULTS: HUC-MSCs increased the number (10.75 ± 1.50) in the DEN/TCPOBOP-induced mice hepatoma model, compared with DMSO group (7.25 ± 1.71). Moreover, the liver index in hUC-MSCs group (0.21 ± 0.06) was greater than that in DMSO group (0.09 ± 0.01). Immunohistochemical (IHC) analysis revealed that while hUC-MSCs did not alter Foxp3 expression, they significantly stimulated Ki67 expression, indicative of increased tumor cellular proliferation. Additionally, immunofluorescence (IF) studies showed that hUC-MSCs increased CD8+ T cell counts without affecting macrophage numbers. Notably, granzyme B expression remained nearly undetectable. We observed that serum IL-18 levels were higher in the hUC-MSCs group (109.66 ± 0.38 pg/ml) compared to the DMSO group (91.14 ± 4.37 pg/ml). Conversely, IL-1ß levels decreased in the hUC-MSCs group (63.00 ± 0.53 pg/ml) relative to the DMSO group (97.38 ± 9.08 pg/ml). CONCLUSIONS: According to this study, hUC-MSCs promoted the growth of liver tumors. Therefore, we proposed that hUC-MSCs are not suitable for treating HCC, as they exhibit clinically prohibited abnormalities.


Assuntos
Carcinoma Hepatocelular , Proliferação de Células , Interleucina-18 , Neoplasias Hepáticas , Células-Tronco Mesenquimais , Cordão Umbilical , Células-Tronco Mesenquimais/metabolismo , Humanos , Animais , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/metabolismo , Cordão Umbilical/citologia , Interleucina-18/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Camundongos , Transplante de Células-Tronco Mesenquimais/métodos , Masculino , Linhagem Celular Tumoral , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia
3.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1295-1309, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38621977

RESUMO

The aim of this study was to explore the mechanism of icaritin-induced ferroptosis in hepatoma HepG2 cells. By bioinformatics screening, the target of icariin's intervention in liver cancer ferroptosis was selected, the protein-protein interaction(PPI) network was constructed, the related pathways were focused, the binding ability of icariin and target protein was evaluated by molecular docking, and the impact on patients' survival prognosis was predicted and the clinical prediction model was built. CCK-8, EdU, and clonal formation assays were used to detect cell viability and cell proliferation; colorimetric method and BODIPY 581/591 C1 fluorescent probe were used to detect the levels of Fe~(2+), MDA and GSH in cells, and the ability of icariin to induce HCC cell ferroptosis was evaluated; RT-qPCR and Western blot detection were used to verify the mRNA and protein levels of GPX4, xCT, PPARG, and FABP4 to determine the expression changes of these ferroptosis-related genes in response to icariin. Six intervention targets(AR, AURKA, PPARG, AKR1C3, ALB, NQO1) identified through bioinformatic analysis were used to establish a risk scoring system that aids in estimating the survival prognosis of HCC patients. In conjunction with patient age and TNM staging, a comprehensive Nomogram clinical prediction model was developed to forecast the 1-, 3-, and 5-year survival of HCC patients. Experimental results revealed that icariin effectively inhibited the activity and proliferation of HCC cells HepG2, significantly modulating levels of Fe~(2+), MDA, and lipid peroxidation ROS while reducing GSH levels, hence revealing its potential to induce ferroptosis in HCC cells. Icariin was found to diminish the expression of GPX4 and xCT(P<0.01), inducing ferroptosis in HCC cells, potentially in relation to inhibition of PPARG and FABP4(P<0.01). In summary, icariin induces ferroptosis in HCC cells via the PPARG/FABP4/GPX4 pathway, providing an experimental foundation for utilizing the traditional Chinese medicine icariin in the prevention or treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Flavonoides , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , PPAR gama , Células Hep G2 , Modelos Estatísticos , Simulação de Acoplamento Molecular , Prognóstico , Proteínas de Ligação a Ácido Graxo
4.
Heliyon ; 10(5): e27151, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38495207

RESUMO

The development of immune checkpoint inhibitors (ICIs) has significantly advanced cancer treatment. However, their efficacy is not consistent across all patients, underscoring the need for personalized approaches. In this study, we examined the relationship between activated CD4+ memory T cell expression and ICI responsiveness. A notable correlation was observed between increased activated CD4+ memory T cell expression and better patient survival in various cohorts. Additionally, the chemokine CXCL13 was identified as a potential prognostic biomarker, with higher expression levels associated with improved outcomes. Further analysis highlighted CXCL13's role in influencing the Tumor Microenvironment, emphasizing its relevance in tumor immunity. Using these findings, we developed a deep learning model by the Multi-Layer Aggregation Graph Neural Network method. This model exhibited promise in predicting ICI treatment efficacy, suggesting its potential application in clinical practice.

5.
Funct Integr Genomics ; 24(2): 63, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38517555

RESUMO

The TRIM family is associated with the membrane, and its involvement in the progression, growth, and development of various cancer types has been researched extensively. However, the role played by the TRIM5 gene within this family has yet to be explored to a great extent in terms of hepatocellular carcinoma (HCC). The data of patients relating to mRNA expression and the survival rate of individuals diagnosed with HCC were extracted from The Cancer Genome Atlas (TCGA) database. UALCAN was employed to examine the potential link between TRIM5 expression and clinicopathological characteristics. In addition, enrichment analysis of differentially expressed genes (DEGs) was conducted as a means of deciphering the function and mechanism of TRIM5 in HCC. The data in the TCGA and TIMER2.0 databases was utilized to explore the correlation between TRIM5 and immune infiltration in HCC. WGCNA was performed as a means of assessing TRIM5-related co-expressed genes. The "OncoPredict" R package was also used for investigating the association between TRIM5 and drug sensitivity. Finally, qRT-PCR, Western blotting (WB) and immunohistochemistry (IHC) were employed for exploring the differential expression of TRIM5 and its clinical relevance in HCC. According to the results that were obtained from the vitro experiments, mRNA and protein levels of TRIM5 demonstrated a significant upregulation in HCC tissues. It is notable that TRIM5 expression levels were found to have a strong association with the infiltration of diverse immune cells and displayed a positive correlation with several immune checkpoint inhibitors. The TRIM5 expression also displayed promising clinical prognostic value for HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Expressão Gênica , RNA Mensageiro , Biomarcadores , Proteínas com Motivo Tripartido/genética , Fatores de Restrição Antivirais , Ubiquitina-Proteína Ligases
6.
Eur Radiol ; 34(1): 509-524, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37507611

RESUMO

OBJECTIVES: To investigate the efficiency of a combination of preoperative contrast-enhanced computed tomography (CECT) and carbohydrate antigen 19-9 (CA19-9) in predicting disease-free survival (DFS) after R0 resection of pancreatic ductal adenocarcinoma (PDAC). METHODS: A total of 138 PDAC patients who underwent curative R0 resection were retrospectively enrolled and allocated chronologically to training (n = 91, January 2014-July 2019) and validation cohorts (n = 47, August 2019-December 2020). Using univariable and multivariable Cox regression analyses, we constructed a preoperative clinicoradiographic model based on the combination of CECT features and serum CA19-9 concentrations, and validated it in the validation cohort. The prognostic performance was evaluated and compared with that of postoperative clinicopathological and tumor-node-metastasis (TNM) models. Kaplan-Meier analysis was conducted to verify the preoperative prognostic stratification performance of the proposed model. RESULTS: The preoperative clinicoradiographic model included five independent prognostic factors (tumor diameter on CECT > 4 cm, extrapancreatic organ infiltration, CECT-reported lymph node metastasis, peripheral enhancement, and preoperative CA19-9 levels > 180 U/mL). It better predicted DFS than did the postoperative clinicopathological (C-index, 0.802 vs. 0.787; p < 0.05) and TNM (C-index, 0.802 vs. 0.711; p < 0.001) models in the validation cohort. Low-risk patients had significantly better DFS than patients at the high-risk, defined by the model preoperatively (p < 0.001, training cohort; p < 0.01, validation cohort). CONCLUSIONS: The clinicoradiographic model, integrating preoperative CECT features and serum CA19-9 levels, helped preoperatively predict postsurgical DFS for PDAC and could facilitate clinical decision-making. CLINICAL RELEVANCE STATEMENT: We constructed a simple model integrating clinical and radiological features for the prediction of disease-free survival after curative R0 resection in patients with pancreatic ductal adenocarcinoma; this novel model may facilitate preoperative identification of patients at high risk of recurrence and metastasis that may benefit from neoadjuvant treatments. KEY POINTS: • Existing clinicopathological predictors for prognosis in pancreatic ductal adenocarcinoma (PDAC) patients who underwent R0 resection can only be ascertained postoperatively and do not allow preoperative prediction. • We constructed a clinicoradiographic model, using preoperative contrast-enhanced computed tomography (CECT) features and preoperative carbohydrate antigen 19-9 (CA19-9) levels, and presented it as a nomogram. • The presented model can predict disease-free survival (DFS) in patients with PDAC better than can postoperative clinicopathological or tumor-node-metastasis (TNM) models.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Antígeno CA-19-9 , Intervalo Livre de Doença , Estudos Retrospectivos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/cirurgia , Prognóstico , Tomografia Computadorizada por Raios X/métodos , Carboidratos
7.
J Neurol Surg A Cent Eur Neurosurg ; 85(1): 62-73, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36640757

RESUMO

BACKGROUND: With the rapid development of science and technology, artificial intelligence (AI) has been widely used in the diagnosis and prognosis of various spine diseases. It has been proved that AI has a broad prospect in accurate diagnosis and treatment of spine disorders. METHODS: On May 7, 2022, the Web of Science (WOS) Core Collection database was used to identify the documents on the application of AI in the field of spine care. HistCite and VOSviewer were used for citation analysis and visualization mapping. RESULTS: A total of 693 documents were included in the final analysis. The most prolific authors were Karhade A.V. and Schwab J.H. United States was the most productive country. The leading journal was Spine. The most frequently used keyword was spinal. The most prolific institution was Northwestern University in Illinois, USA. Network visualization map showed that United States was the largest network of international cooperation. The keyword "machine learning" had the strongest total link strengths (TLS) and largest number of occurrences. The latest trends suggest that AI for the diagnosis of spine diseases may receive widespread attention in the future. CONCLUSIONS: AI has a wide range of application in the field of spine care, and an increasing number of scholars are committed to research on the use of AI in the field of spine care. Bibliometric analysis in the field of AI and spine provides an overall perspective, and the appreciation and research of these influential publications are useful for future research.


Assuntos
Inteligência Artificial , Doenças da Coluna Vertebral , Humanos , Coluna Vertebral , Doenças da Coluna Vertebral/terapia , Bibliometria , Cooperação Internacional
8.
J Thorac Cardiovasc Surg ; 167(2): 498-507.e2, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37301252

RESUMO

OBJECTIVE: To compare the efficacy and safety of preoperative localization of small pulmonary nodules (SPNs) with 4-hook anchor device and hook-wire before video-assisted thoracoscopic surgery. METHODS: Patients with SPNs scheduled for computed tomography-guided nodule localization before video-assisted thoracoscopic surgery between May 2021 and June 2021 at our center were randomized to either 4-hook anchor group or hook-wire group. The primary end point was intraoperative localization success. RESULTS: After randomization, 28 patients with 34 SPNs were assigned to the 4-hook anchor group and 28 patients with 34 SPNs to the hook-wire group. The operative localization success rate was significantly greater in the 4-hook anchor group than in the hook-wire group (94.1% [32/34] vs 64.7% [22/34]; P = .007). All lesions in the 2 groups were successfully resected under thoracoscopy, but 4 patients in the hook-wire group who required transition from wedge resection to segmentectomy or lobectomy because of unsuccessful localization. Total localization-related complication rate was significantly lower in the 4-hook anchor group than in the hook-wire group (10.3% [3/28] vs 50.0% [14/28]; P = .004). The rate of chest pain requiring analgesia after the localization procedure was significantly lower in the 4-hook anchor group than in the hook-wire group (0 vs 5/28, 17.9%; P = .026). There were no significant differences in localization technical success rate, operative blood loss, hospital stay length and hospital cost between the 2 groups (all P > .05). CONCLUSIONS: The use of the 4-hook anchor device for SPN localization offers advantages over the traditional hook-wire technique.


Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Nódulo Pulmonar Solitário , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/cirurgia , Nódulos Pulmonares Múltiplos/patologia , Estudos Retrospectivos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/cirurgia , Nódulo Pulmonar Solitário/patologia , Cirurgia Torácica Vídeoassistida/métodos , Tomografia Computadorizada por Raios X/métodos
9.
Appl Physiol Nutr Metab ; 49(3): 319-329, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37922515

RESUMO

People living with human immunodeficiency virus (PLWH) have persistent malnutrition, intestinal barrier dysfunction, and gut microbial imbalance. The interplay between gut microbiota and nutrients is involved in the immune reconstitution of PLWH. To evaluate the effects of whole-protein enteral nutrition formula supplementation on T-cell levels, intestinal barrier function, nutritional status, and gut microbiota composition in human immunodeficiency virus (HIV)-infected immunological nonresponders (INRs) who failed to normalize CD4+ T-cell counts, with a number <350 cells/µL, a pilot study was carried out in 13 HIV-infected INRs undergoing antiretroviral therapy who received a 3-month phase supplementation of 200 mL/200 kcal/45 g whole-protein enteral nutrition formula once daily. Our primary endpoint was increased CD4+ T-cell counts. Secondary outcome parameters were changes in intestinal barrier function, nutritional status, and gut microbiota composition. We showed that CD4+ T-cell counts of HIV-infected INRs increased significantly after the 3-month supplementation. Dietary supplementation for 3 months improved the intestinal barrier function and nutritional status of HIV-infected INRs. Furthermore, the enteral nutrition formula significantly decreased the relative abundance of Escherichia at the genus level and increased the alpha diversity of gut microbiota in HIV-infected INRs. The findings demonstrated that the whole-protein enteral nutrition formula aids in reducing Escherichia and improving intestinal barrier function in HIV-infected INRs. This study provides insight into the role of nutrients in the improvement of immune reconstitution in HIV-infected INRs. This study is registered in the Chinese Clinical Trial Registry (Document No. ChiCTR2000037839; http://www.chictr.org.cn/index.aspx).


Assuntos
Infecções por HIV , HIV , Humanos , Nutrição Enteral , Função da Barreira Intestinal , Projetos Piloto , Infecções por HIV/terapia , Suplementos Nutricionais
10.
J Neurol Surg A Cent Eur Neurosurg ; 85(3): 280-287, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37586408

RESUMO

BACKGROUND: Tranexamic acid (TXA) is safe and effective in preventing bleeding during spinal surgery. However, there is currently no relevant research on the efficacy and safety of adding TXA to the saline irrigation fluid in percutaneous endoscopic interlaminar diskectomy (PEID). This study aimed to evaluate the efficacy and safety of topical saline irrigation with TXA for PEID in the treatment of lumbar disk herniation. METHODS: In this single-center, retrospective cohort study, patients who underwent PEID for L5-S1 lumbar disk herniation were included and allocated to two groups according to whether they had been administered TXA. PEID was performed with saline irrigation fluid containing 0.33 g of TXA per 1 L of saline in the TXA group (n = 38). In the control group (n = 51), the saline irrigation fluid was injected with the same volume of normal saline. All PEIDs were performed by the same spine surgery team. The hidden blood loss (HBL), intraoperative blood loss (IBL), total blood loss (TBL), amount of fluid used, operation time, visual clarity, hospital stay, blood transfusion rate, coagulation index, and complication rate were compared between the two groups. RESULTS: The TBL, HBL, and IBL in the TXA group were significantly lower than those of the control group. The postoperative hemoglobin in the TXA group was significantly higher than that of the control group. Visual clarity was significantly better and the operation time was significantly shorter in the TXA group. However, there was no significant difference in postoperative hematocrit, blood coagulation function, amount of fluid used, blood transfusion rate, and perioperative complications between the two groups. CONCLUSION: In PEID, the addition of TXA to topical saline irrigating fluid can significantly reduce the HBL, IBL, and TBL. The addition of TXA to topical saline irrigating fluid can improve visual clarity in the surgery and reduce operation time, but it does not change the coagulation function or the complication rate.


Assuntos
Antifibrinolíticos , Discotomia Percutânea , Deslocamento do Disco Intervertebral , Ácido Tranexâmico , Humanos , Ácido Tranexâmico/uso terapêutico , Estudos Retrospectivos , Perda Sanguínea Cirúrgica/prevenção & controle , Antifibrinolíticos/uso terapêutico , Deslocamento do Disco Intervertebral/cirurgia , Solução Salina , Resultado do Tratamento
11.
Clin J Pain ; 40(2): 114-123, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37982694

RESUMO

OBJECTIVES: As 2 novel peripheral nerve blocks, the erector spinae plane block (ESPB) and thoracolumbar interfascial plane (TLIP) block can relieve postoperative pain in spinal surgery. This systematic review and meta-analysis aimed to determine the efficacy and safety of ESPB versus TLIP block in patients undergoing spine surgery. METHODS: An extensive search of English online databases, including PubMed, Web of Sciences, Embase, Medline, and Cochrane Central Register of Controlled Trials, and Chinese online databases like Wanfang Data, CNKI, and CQVIP until March 31, 2023, with no language restrictions, was performed. This systematic review and meta-analysis are based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and have been registered on PROSPERO (International Prospective Register of Systematic Reviews) with registered ID: CRD42023420987. RESULTS: Five studies involving 457 patients were eligible for inclusion in this study. Compared with TLIP block, ESPB had lower postoperative opioid consumption at postoperative 48 hours (standard mean difference =-1.31, 95% CI:-2.54 to -0.08, P =0.04, I2 =80%) and postoperative pain score at postoperative 24 hours (standard mean difference =-0.72, 95% CI=-1.43 to -0.02, P =0.04, I2 =95%) in patients undergoing spine surgery. Complications associated with ESPB and TLIP block were not reported in the included studies. DISCUSSION: ESPB and TLIP block are 2 novel and effective block methods. Patients receiving ESPB had lower postoperative opioid consumption and postoperative pain scores compared with patients receiving TLIP block; there was no statistically significant difference's between the 2 groups in intraoperative opioid consumption, adverse events, and rescue analgesia.


Assuntos
Bloqueio Nervoso , Humanos , Analgésicos Opioides , Dor Pós-Operatória/tratamento farmacológico
12.
Biomed Pharmacother ; 170: 116001, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38128182

RESUMO

Intervertebral disc degeneration (IVDD) is a main cause of low back pain (LBP), which can lead to disability and thus generate a heavy burden on society. IVDD is characterized by a decrease in nucleus pulposus cells (NPCs) and endogenous mesenchymal stem cells (MSCs), degradation of the extracellular matrix, macrophage infiltration, and blood vessel and nerve ingrowth. To date, the therapeutic approaches regarding IVDD mainly include conservative treatment and surgical intervention. However, both can only relieve symptoms rather than stop or revert the progression of IVDD, since the pathogenesis of IVDD is not yet clear. Pyroptosis, which is characterized by Caspase family dependence and conducted by the Gasdermin family, is a newly discovered mode of programmed cell death. Pyroptosis has been observed in NPCs, annulus fibrosus cells (AFCs), chondrocytes, MSCs, macrophages, vascular endothelial cells and neurons and may contribute to IVDD. MSCs are a kind of pluripotent stem cell that can be found in almost all tissues. MSCs have a strong ability to secrete extracellular vesicles (EVs), which contain exosomes, microvesicles and apoptotic bodies. EVs derived from MSCs play an important role in pyroptosis regulation and could be beneficial for alleviating IVDD. This review focuses on clarifying the regulation of pyroptosis to improve IVDD by MSCs and EVs derived from MSCs.


Assuntos
Vesículas Extracelulares , Degeneração do Disco Intervertebral , Disco Intervertebral , Células-Tronco Mesenquimais , Núcleo Pulposo , Humanos , Piroptose , Células Endoteliais , Degeneração do Disco Intervertebral/terapia
13.
Clin Exp Rheumatol ; 42(2): 237-245, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38153165

RESUMO

OBJECTIVES: Anti-MDA5+ dermatomyositis was associated with poor prognosis due to the high incidence of rapid progressive interstitial lung disease, pulmonary infection. The aim of this study is to investigate the abundance and clinical relevance of exhaustion markers on peripheral CD8 T cells from patients with idiopathic inflammatory myopathy (IIM). METHODS: Twenty-nine healthy controls (HCs) and 71 patients with IIM were enrolled, including 42 with anti-MDA5+ and 18 with anti-MDA5- dermatomyositis (DM) and 11 with anti-synthetase syndrome (ASS). Flow cytometry was applied to detect PD-1, TIM-3 and LAG-3 in CD8 T cells. The clinical associations of the CD8 T cell exhaustion phenotype in patients with anti-MDA5+ DM were analysed. RESULTS: CD8 T cells from patients with anti-MDA5+ DM showed significantly increased LAG-3, TIM-3 and PD-1 compared to those from patients with anti-MDA5- IIM (18 with anti-MDA5- DM and 11 with ASS) or HCs (adjusted p all < 0.05). CD8 T cells with distinct exhaustion levels were all significantly increased in anti-MDA5+ DM patients compared with HCs (p all < 0.05). Patients with high level of PD-1+ TIM-3+LAG-3+ CD8+ T cells had a significant higher incidence of pulmonary fungal infections but lower counts of CD4+ and CD8+ T cells. ROC analysis revealed that the frequency of PD-1+TIM-3+LAG-3+CD8+ T cell significantly predicted pulmonary fungal infections (area under the curve: 0.828). CONCLUSIONS: CD8 T cells from patients with anti-MDA5+ DM show significant exhausted phenotype, and increased exhausted CD8 T cells were associated with high risk of pulmonary fungal infection.


Assuntos
Dermatomiosite , Humanos , Dermatomiosite/complicações , Receptor Celular 2 do Vírus da Hepatite A , Helicase IFIH1 Induzida por Interferon , Receptor de Morte Celular Programada 1 , Autoanticorpos , Linfócitos T CD8-Positivos , Linfócitos T , Estudos Retrospectivos , Prognóstico
14.
iScience ; 26(12): 108394, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38047064

RESUMO

To guide individualized intensity-modulated radiotherapy (IMRT), we developed and prospectively validated a multiview radiomics risk model for predicting radiation-induced hypothyroidism in patients with nasopharyngeal carcinoma. And simulated radiotherapy plans with same dose-volume-histogram (DVH) but different dose distributions were redesigned to explore the clinical application of the multiview radiomics risk model. The radiomics and dosiomics were built based on selected radiomics and dosiomics features from planning computed tomography and dose distribution, respectively. The multiview radiomics risk model that integrated radiomics, dosiomics, DVH parameters, and clinical factors had better performance than traditional normal tissue complication probability models. And multiview radiomics risk model could identify differences of patient hypothyroidism-free survival that cannot be stratified by traditional models. Besides, two redesigned simulated plans further verified the clinical application and advantage of the multiview radiomics risk model. The multiview radiomics risk model was a promising method to predict radiation-induced hypothyroidism and guide individualized IMRT.

15.
Clin Med Insights Oncol ; 17: 11795549231201129, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37928452

RESUMO

Background: Although radioisotope (RI) combined with blue dye (BD) is the standard technique for sentinel lymph node (SLN) biopsy in breast cancer, the use of RI is limited at some institutions due to the specific equipment needed. Indocyanine green (ICG) fluorescence detection has been developed as a potential substitute for RI method. However, reports on the sensitivity of ICG and RI techniques in detecting SLN are inconsistent; hence, the present study was designed to compare the clinical efficacy between the combined method of ICG + BD (ICG-B) and RI + BD (RI-B). Methods: A prospective observational study was performed that identified 138 breast cancer patients who had undergone lymphatic mapping and SLN biopsy with ICG-B or RI-B. The SLN detection rate, positive SLN counts, and lymph node metastasis between the 2 groups were compared. Results: A total of 71 patients were recruited in the ICG-B group, while 67 were recruited in the RI-B group. The SLN detection rate was 100% in both the ICG-B and RI-B groups. Lymph node metastasis was found in 13 patients using ICG-B and in 12 patients using the RI-B technique (18.31% vs 17.91%, respectively; P = .61). No significant differences were observed in the positive SLN counts (3.12 ± 2.01 vs 3.33 ± 2.24, P = .37) between the 2 groups. Conclusions: Indocyanine green combined with BD has an equal efficacy compared with RI plus BD when performing an axillary SLN biopsy in breast cancer. The ICG plus BD procedure is a promising alternative to traditional standard mapping methods.

16.
Oral Oncol ; 147: 106583, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37837738

RESUMO

BACKGROUND: To demonstrate whether the benefit of locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma remains in the immunotherapy era and which patients can benefit from radiotherapy. MATERIALS AND METHODS: A total of 273 histopathology-confirmed de novo metastatic nasopharyngeal carcinoma was enrolled between May 2017 and October 2021 if receiving immunochemotherapy with or without subsequent intensity-modulated radiotherapy to the nasopharynx and neck. We compared the progression-free survival, overall survival, and safety between the two groups. Additionally, subgroup analysis was conducted and a scoring model was developed to identify suitable patients for radiation. RESULTS: There were 95 (34.8 %) patients with immunochemotherapy alone, and 178 (65.2 %) with immunochemotherapy plus subsequent locoregional radiotherapy. With a median follow-up time of 18 months, patients with immunochemotherapy plus subsequent radiotherapy had higher 1-year progression-free survival (80.6 % vs. 65.1 %, P < 0.001) and overall survival (98.3 % vs. 89.5 %, P = 0.001) than those with immunochemotherapy alone. The benefit was retained in multivariate analysis and propensity score-matched analysis. Mainly, it was more significant in patients with oligometastases, EBV DNA below 20,200 copies/mL, and complete or partial relapse after immunochemotherapy. The combined treatment added grade 3 or 4 anemia and radiotherapy-related toxicities. CONCLUSION: Immunochemotherapy plus subsequent locoregional radiotherapy prolonged the survival of de novo metastatic nasopharyngeal carcinoma with tolerable toxicities. A scoring model based on oligometastases, EBV DNA level, and response after immunochemotherapy could facilitate individualized management.


Assuntos
Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Humanos , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Resultado do Tratamento , Estudos Retrospectivos , Recidiva Local de Neoplasia/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Imunoterapia , DNA/uso terapêutico
17.
Molecules ; 28(20)2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37894659

RESUMO

Exploring the properties of magnetic metal on the semiconductor surface is of great significance for the application of magnetic recording materials. Herein, DFT calculations are carried out to explore the properties of the iron-silicon interface structures (nFe/DASF) formed by depositing n Fe atoms on the reconstructed Si(111)-(7×7) surface (DASF). The stable nFe/DASF structures are studied in the cases of the adsorption and permeation of Fe atoms on the DASF. In both cases, Fe atoms are not very dispersed and prefer binding with Si atoms rather than the adsorbed Fe atoms, because the Fe-Si interaction is stronger than the Fe-Fe interaction. As the n value increases, the average binding energy (Eb_ave) of Fe generally firstly becomes more negative and then becomes less negative, with the presence of a 7Fe wheel as a stable geometry on the upmost surface. The presence of the 7Fe wheel is attributed to the enhanced Fe-Si interaction in this wheel compared to other geometries. CO adsorption occurs at the central Fe site of the 7Fe wheel which is greatly influenced by the surrounding Si atoms but is little influenced by the additional Fe atoms in the interlayer.

18.
J Tissue Eng ; 14: 20417314231200328, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37736245

RESUMO

Acute liver failure (ALF) is characterized by rapid liver cell destruction. It is a multi-etiological and fulminant complication with a clinical mortality of over 80%. Therapy using mesenchymal stem cells (MSCs) or MSCs-derived exosomes can alleviate acute liver injury, which has been demonstrated in animal experiments and clinical application. However, similar to other stem cells, different cell sources, poor stability, cell senescence and other factors limit the clinical application of MSCs. To achieve mass production and quality control on stem cells and their exosomes, transfecting umbilical cord mesenchymal stem cell (UCMSC) with lentivirus overexpressing human telomerase reverse transcriptase (hTERT) gene, the hTERT-UCMSC was constructed as an immortalized MSC cell line. Compared with the primary UCMSC (P3) and immortalized cell line hTERT-UCMSC at early passage (P10), the hTERT-UCMSC retained the key morphological and physiological characteristics of UCMSC at the 35th passage (P35), and showed no signs of carcinogenicity and toxic effect in mice. There was no difference in either exosome production or characteristics of exosomes among cultures from P3 primary cells, P10 and P35 immortalized hTERT-UCMSCs. Inoculation of either hTERT-UCMSC (P35) or its exosomes improved the survival rate and liver function of ALF mice induced by thioacetamide (TAA). Our findings suggest that this immortalized cell line can maintain its characteristics in long-term culture. Inoculation of hTERT-UCMSC and its exosomes could potentially be used in clinics for the treatment of liver failure in the future.

19.
Nanotechnology ; 35(1)2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37774685

RESUMO

Interactions between ultrafast lasers and metal targets are crucial in various laser micro/nano-machinings. However, the underlying incubation and absorption-enhancement mechanisms remain elusive, which hinders the quality control of laser processing. Herein, we studied the incubation effect and absorption enhancement during multi-shot femtosecond-laser ablations via combining experiments and hydrodynamic simulations, taking aluminum alloy and stainless steels as paradigm materials. Accumulation effects of heat and damage-induced deformation were revealed by the evolutions of microstructures induced by low-energy femtosecond lasers. The calculated ablation thresholds were reduced with shot number, demonstrating the incubation effect. Calculation of threshold fluence via crater diameter is better than ablation depth, because that the latter is determined by different parameters at low- and high-energy conditions. Experimental observations and hydrodynamic simulations indicated that the enhanced absorption could be attributed to several factors, including laser-induced surface micro/sub-micro structures, photoionization, and plasma evolutions.

20.
Bioeng Transl Med ; 8(5): e10552, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37693041

RESUMO

Acute liver failure (ALF) is a life-threatening condition. Cell-based and cell-free-based therapies have proven to be effective in treating ALF; however, their clinical application is limited by cell tumorigenicity and extracellular vesicle (EV) isolation in large doses. Here, we explored the effectiveness and mechanism of umbilical cord mesenchymal stem cells (hUCMSCs)-based bioartificial liver (hUCMSC-BAL), which is a simple and efficient strategy for ALF. D-galactosamine-based pig and mouse ALF models were used to explore the effectiveness of hUCMSC-BAL and hUCMSC-sEV therapies. Furthermore, high-throughput sequencing, miRNA transcriptome analysis, and western blot were performed to clarify whether the miR-139-5p/PDE4D axis plays a critical role in the ALF model in vivo and in vitro. hUCMSC-BAL significantly reduced inflammatory responses and cell apoptosis. hUCMSC-sEV significantly improved liver function in ALF mice and enhanced the regeneration of liver cells. Furthermore, hUCMSC-sEV miRNA transcriptome analysis showed that miR-139-5p had the highest expression and that PDE4D was one of its main target genes. The sEV miR-139-5p/PDE4D axis played a role in the treatment of ALF by inhibiting cell apoptosis. Our data indicate that hUCMSC-BAL can inhibit cytokine storms and cell apoptosis through the sEV miR-139-5p/PDE4D axis. Therefore, we propose hUCMSC-BAL as a therapeutic strategy for patients with early ALF.

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