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1.
Front Neurol ; 15: 1361151, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38645741

RESUMO

Background: For nonmoyamoya patients with anterior cerebral artery (ACA) stenosis or occlusion, whether direct revascularization of the ACA territory can prevent stroke is still unclear. The objective of this study was to investigate the efficacy and safety of a parietal branch of superficial temporal artery-interposed superficial temporal artery-to-ACA bypass (PISAB) for preventing stroke in patients with symptomatic atherosclerotic ACA stenosis or occlusion (SAASO). Methods: We retrospectively analyzed the data from patients with SAASO who had undergone PISAB in our center between April 2016 and November 2021. The rates of patency, satisfaction (revascularization grades A and B) of bypass, perioperative complications, recurrence of ischemic stroke, changes in bypass flow, and improvements in cerebral blood perfusion were analyzed. Results: A total of 19 SAASO patients were involved in this study. Sixteen out of 19 (84.2%) patients were free from any cerebral ischemic events after surgery. Only 3 patients (15.8%) had recurrent stroke postoperatively. Two (10.5%) surgery-related complications occurred, including hyperperfusion syndrome and minor stroke. No skin ischemic complications occurred. The average follow-up period was 50.6 ± 18.3 months. The flow rate of the bypass was significantly increased half a year after surgery (56.2 ± 8.0 mL/min vs. 44.3 ± 5.3 mL/min, p < 0.001). The ratio of ipsilateral/contralateral mean transit time in the superior frontal gyrus was decreased significantly after bypass (1.08 ± 0.07 vs. 1.23 ± 0.05, p < 0.001) and continued to decrease 6 months after surgery (1.05 ± 0.04 vs. 1.08 ± 0.07, p = 0.002). The patency rate of PISAB was 94.7% (18/19) 2 years after surgery. The satisfaction rate of bypass was 89.5% (17/19). Conclusion: The results of this study indicate that PISAB, as a safe superficial bypass, can effectively reduce the risk of stroke in SAASO patients. More precise conclusions will require randomized control studies.

2.
Neurotherapeutics ; : e00347, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38570276

RESUMO

Berberine (BBR) has demonstrated potent anti-inflammatory effects by modulating macrophage polarization. Nevertheless, the precise mechanisms through which berberine regulates post-injury inflammation within the peripheral nerve system remain elusive. This study seeks to elucidate the role of BBR and its underlying mechanisms in inflammation following peripheral nerve injury (PNI). Adult male C57BL/6J mice subjected to PNI were administered daily doses of berberine (0, 60, 120, 180, 240 â€‹mg/kg) via gavage from day 1 through day 28. Evaluation of the sciatic function index (SFI) and paw withdrawal threshold revealed that BBR dose-dependently enhanced both motor and sensory functions. Immunofluorescent staining for anti-myelin basic protein (anti-MBP) and anti-neurofilament-200 (anti-NF-200), along with histological staining comprising hematoxylin-eosin (HE), luxol fast blue (LFB), and Masson staining, demonstrated that BBR dose-dependently promoted structural regeneration. Molecular analyses including qRT-PCR, Western blotting, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence confirmed that inactivation of the NLRP3 inflammasome by MCC950 shifted macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, while also impeding macrophage infiltration. Furthermore, BBR significantly downregulated the expression of the NLRP3 inflammasome and its associated molecules in macrophages, thereby mitigating NLRP3 inflammasome activation-induced macrophage M1 polarization and inflammation. In summary, BBR's neuroprotective effects were concomitant with the suppression of inflammation after PNI, achieved through the inhibition of NLRP3 inflammasome activation-induced macrophage M1 polarization.

3.
Endocr Connect ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38579756

RESUMO

To optimize the treatment plan for patients with type 2 diabetes mellitus (T2DM) and hyperuricemia, this narrative literature review summarizes the effect of antidiabetic drugs on serum uric acid (SUA) levels using data from observational studies, prospective clinical trials, post-hoc analyses and meta-analyses. SUA is an independent risk factor for T2DM, and evidence has shown that patients with both gout and T2DM exhibit a mutually interdependent effect on higher incidences. We find that insulin and dipeptidyl peptidase 4 inhibitor (DPP-4i) except linagliptin could increase the SUA, and other drugs including metformin, thiazolidinediones (TZDs), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), linagliptin, sodium-glucose cotransporter 2 inhibitors (SGLT2i) and α-glucosidase inhibitors have a reduction effect on SUA. We explain the mechanisms of different antidiabetic drugs above on SUA and analyze them compared with actual data. For sulfonylureas, meglitinides, and amylin analogs, the underlying mechanism remains unclear. We think the usage of linagliptin and SGLT2i is the most potentially effective treatment of patients with T2DM and hyperuricemia currently. Our review is a comprehensive summary of the effects of antidiabetic drugs on SUA, which includes actual data, the mechanisms of SUA regulation, and the usage rate of drugs.

4.
Molecules ; 29(7)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38611708

RESUMO

In this study, the separation conditions of UHPLC-QTOF-MS and the extraction conditions of QuEChERS were optimized. The analytical process for determining Broflanilide residues in different soil types was successfully established and applied to its adsorption, desorption, and leaching in soil. Broflanilide was extracted from soil with acetonitrile and purified using PSA and MgSO4. The modified UHPLC-QTOF-MS method was used for quantification. The average recovery of Broflanilide was between 87.7% and 94.38%, with the RSD lower than 7.6%. In the analysis of adsorption, desorption, and leaching quantities in four soil types, the RSD was less than 9.2%, showing good stability of the method, which can be applied to determine the residue of Broflanilide in different soils.

5.
Clin Exp Rheumatol ; 2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38436296

RESUMO

OBJECTIVES: The aberrant expression of omentin-1 had been reported in type 2 diabetes and cardiovascular disease. Here, we investigated the expression and role of omentin-1 in rheumatoid arthritis (RA). METHODS: The expression of omentin-1 in RA and in the normal population was detected by ELISA and immunohistochemistry, and collagen-induced arthritis (CIA) mice were used to detect the role of omentin-1 in RA. RESULTS: We found that the expression of omentin-1 was elevated in serum of RA patients compared with healthy controls (p=0.004), and in the RA disease activity group compared with the disease remission group (p<0.001). In addition, the level of omentin-1 in RA patients was positively correlated with CRP (r=0.427, p=0.002), ESR (r=0.454, p<0.001) and DAS28 (r=0.496, p<0.001; r=0.661, p<0.001, respectively). Multivariable analysis showed that omentin-1 alone was associated with disease activity state (OR=1.018, p=0.004). Immunohistochemical results showed that omentin-1 was increased in the synovium of RA and CIA mice. Omentin-1 injection resulted in an earlier onset of arthritis, an aggravated arthritic progression, more severe synovial hyperplasia and bone erosion in CIA mice. Moreover, omentin-1 treatment markedly enhanced IL-6, TNF-α, MMP-3, MMP-13 and RANKL in the joint tissue of CIA mice. CONCLUSIONS: Our results suggested that omentin-1 was up-regulated in RA and can exacerbate synovitis and joint destruction which may provide new insight into the pathogenesis of RA.

6.
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.

7.
Int J Endocrinol ; 2023: 5532778, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38131034

RESUMO

Objective: In this study, we aimed to estimate the impact of sleep duration on left ventricular hypertrophy (LVH) in type 2 diabetes mellitus (T2DM). Methods: Consecutive patients with T2DM undergoing transthoracic echocardiography (TTE) in our center from October 2017 to February 2021 were analyzed. The association of the risk of LVH in T2DM patients was evaluated using univariable and multivariable logistic regression analyses. Results: This study finally included 2689 adult patients (mean age 51.8 ± 12.5 years, 56.2% men, mean sleep duration 7.6 ± 1.4 hours per day). Of all patients, 655 (24.4%) patients were diagnosed with LVH and 2034 did not have LVH. All patients were adults and were diagnosed with T2DM. In the univariate and multivariate regression analyses, gender, sleep duration, body mass index (BMI), waist, hemoglobin (Hb), blood creatinine (Cr), and high-density lipoprotein cholesterol (HDL-c) were associated with LVH. In the restricted cubic spline (RCS) model, the cut-off points of sleep duration given refer to the group of patients with T2DM and LVH were 8 hours per day. With the cut-off points, the multivariable analysis demonstrated that, for diabetic patients, LVH was significantly correlated with a sleep duration of 8 hours per day, hemoglobin, blood urea nitrogen (BUN), and HDL-c. Conclusion: For patients with T2DM, long sleep duration (>8 hours per day), hemoglobin, BUN, and HDL-c were independently associated with LVH. This trial is registered with NCT03811470.

8.
Endocr Connect ; 12(11)2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37855329

RESUMO

Osteoporosis (OP) is a systemic bone disease in which bone density and quality decrease and bone fragility increases due to a variety of causes, making it prone to fractures. The development of OP is closely related to oxidative stress. Uric acid (UA) is the end product of purine metabolism in the human body. Extracellular UA has antioxidant properties and is thought to have a protective effect on bone metabolism. However, the process of UA degradation can lead to intracellular oxidative stress, which together with UA-induced inflammatory factors, leads to increased bone destruction. In addition, UA can inhibit vitamin D production, resulting in secondary hyperparathyroidism and further exacerbating UA-associated bone loss. This review summarizes the relationship between serum UA levels and bone mineral density, bone turnover markers, and so on, in the hope of providing new insights into the pathogenesis and treatment of OP.

9.
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
10.
Mar Pollut Bull ; 195: 115468, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37666140

RESUMO

Green tides in the Yellow Sea have occurred periodically since 2007, impacting the ecological environment and green algal communities along the coasts of Jiangsu and Shandong provinces in China. To investigate the morphological characteristics and genetic diversity of Ulva prolifera, we conducted surveys and comparative analyses of both its floating and attached forms along the coastal areas of Jiangsu and Shandong. The results revealed that the external morphology of the floating U. prolifera was multibranched. The attached U. prolifera displayed significant morphological variation among individuals. Based on the analysis of the amplified characteristic bands of the chloroplast gene, it was shown that both floating and attached U. prolifera could hybridize with Ulva linza. The genetic diversity of U. prolifera was studied using mitochondrial and chloroplast genome fragments. All floating U. prolifera and three strains of attached U. prolifera belonged to the same haplotype. The genetic diversity of floating U. prolifera was low, and there were some genetic differences with attached U. prolifera. The attached U. prolifera displayed a higher level of genetic diversity with abundant sites of variation and haplotypes.

11.
EClinicalMedicine ; 63: 102202, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37680944

RESUMO

Background: MRI is the routine examination to surveil the recurrence of nasopharyngeal carcinoma, but it has relatively lower sensitivity than PET/CT. We aimed to find if artificial intelligence (AI) could be competent pre-inspector for MRI radiologists and whether AI-aided MRI could perform better or even equal to PET/CT. Methods: This multicenter study enrolled 6916 patients from five hospitals between September 2009 and October 2020. A 2.5D convolutional neural network diagnostic model and a nnU-Net contouring model were developed in the training and test cohorts and used to independently predict and visualize the recurrence of patients in the internal and external validation cohorts. We evaluated the area under the ROC curve (AUC) of AI and compared AI with MRI and PET/CT in sensitivity and specificity using the McNemar test. The prospective cohort was randomized into the AI and non-AI groups, and their sensitivity and specificity were compared using the Chi-square test. Findings: The AI model achieved AUCs of 0.92 and 0.88 in the internal and external validation cohorts, corresponding to the sensitivity of 79.5% and 74.3% and specificity of 91.0% and 92.8%. It had comparable sensitivity to MRI (e.g., 74.3% vs. 74.7%, P = 0.89) but lower sensitivity than PET/CT (77.9% vs. 92.0%, P < 0.0001) at the same individual-specificities. The AI model achieved moderate precision with a median dice similarity coefficient of 0.67. AI-aided MRI improved specificity (92.5% vs. 85.0%, P = 0.034), equaled PET/CT in the internal validation subcohort, and increased sensitivity (81.9% vs. 70.8%, P = 0.021) in the external validation subcohort. In the prospective cohort of 1248 patients, the AI group had higher sensitivity than the non-AI group (78.6% vs. 67.3%, P = 0.23), albeit nonsignificant. In future randomized controlled trials, a sample size of 3943 patients in each arm would be required to demonstrate the statistically significant difference. Interpretation: The AI model equaled MRI by expert radiologists, and AI-aided MRI by expert radiologists equaled PET/CT. A larger randomized controlled trial is warranted to demonstrate the AI's benefit sufficiently. Funding: The Sun Yat-sen University Clinical Research 5010 Program (2015020), Guangdong Basic and Applied Basic Research Foundation (2022A1515110356), and Guangzhou Science and Technology Program (2023A04J1788).

12.
Front Biosci (Landmark Ed) ; 28(7): 134, 2023 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-37525911

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a group of metabolic liver illnesses that lead to accumulation of liver fat mainly due to excessive nutrition. It is closely related to insulin resistance, obesity, type 2 diabetes, and cardiovascular disease, and has become one of the main causes of chronic liver disease worldwide. At present, there is no specific drug for the treatment of NAFLD; lifestyle interventions including dietary control and exercise are recommended as routine treatments. As a drug for the treatment of type 2 diabetes, sodium-glucose co-transporter type 2 (SGLT-2) inhibitors may also play a beneficial role in the treatment of NAFLD. This article reviews the mechanism of SGLT-2 inhibitors in the treatment of NAFLD.


Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Fígado/metabolismo , Obesidade/metabolismo
13.
BMC Cancer ; 23(1): 677, 2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37464334

RESUMO

The accumulation of lipid droplets (LDs) in hepatocytes is the main pathogenesis in nonalcoholic fatty liver disease (NAFLD), which is also the key risk factor for the progression of hepatocellular carcinoma (HCC). LDs behaviors are demonstrated to be associated with HCC advancement, and are tightly regulated by a subset protein localized on the surface of LDs. However, the role of LDs-localized protein in HCC has been rarely investigated. This study is focused on the transcriptional dynamic and prognostic value of LDs-localized protein in HCC. Firstly, we summarized the known LDs-localized proteins, which are demonstrated by immunofluorescence according to previous studies. Next, by the use of GEPIA/UALCAN/The Human Protein Atlas databases, we screened the transcriptional change in tumor and normal liver tissues, and found that 13 LDs-localized proteins may involve in the progression of HCC. Then we verified the transcriptional changes of 13 LDs-localized proteins by the use of HCC samples. Moreover, based on the assays of fatty liver of mice and human NAFLD liver samples, we found that the hepatic steatosis mainly contributed to the transcriptional change of selected LDs-localized proteins, indicating the involvement of these LDs-localized proteins in the negative role of NAFLD in HCC progression. Finally, we focused on the role of PLIN3 in HCC, and revealed that NAFLD status significantly promoted PLIN3 transcription in HCC tissue. Functional studies revealed that PLIN3 knockdown significantly limited the migration and chemosensitivity of hepatoma cells, suggesting the positive role of PLIN3 in HCC progression. Our study not only revealed the transcriptional change and prognostic value of lipid droplet-localized proteins in HCC, but also built the correlation between HCC and hepatic steatosis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Carcinoma Hepatocelular/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Gotículas Lipídicas/metabolismo , Prognóstico , Proteínas Associadas a Gotículas Lipídicas/metabolismo , Neoplasias Hepáticas/patologia , Proteínas/metabolismo
14.
EClinicalMedicine ; 58: 101930, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37090437

RESUMO

Background: Radiotherapy is the mainstay of treatment for nasopharyngeal carcinoma. Radiation-induced temporal lobe injury (TLI) can regress or resolve in the early phase, but it is irreversible at a later stage. However, no study has proposed a risk-based follow-up schedule for its early detection. Planning evaluation is difficult when dose-volume histogram (DVH) parameters are similar and optimization is terminated. Methods: This multicenter retrospective study included 6065 patients between 2014 and 2018. A 3D ResNet-based deep learning model was developed in training and validation cohorts and independently tested using concordance index in internal and external test cohorts. Accordingly, the patients were stratified into risk groups, and the model-predicted risks were used to develop risk-based follow-up schedules. The schedule was compared with the Radiation Therapy Oncology Group (RTOG) recommendation (every 3 months during the first 2 years and every 6 months in 3-5 years). Additionally, the model was used to evaluate plans with similar DVH parameters. Findings: Our model achieved concordance indexes of 0.831, 0.818, and 0.804, respectively, which outperformed conventional prediction models (all P < 0.001). The temporal lobes in all the cohorts were stratified into three groups with discrepant TLI-free survival. Personalized follow-up schedules developed for each risk group could detect TLI 1.9 months earlier than the RTOG recommendation. According to a higher median predicted 3-year TLI-free survival (99.25% vs. 99.15%, P < 0.001), the model identified a better plan than previous models. Interpretation: The deep learning model predicted TLI more precisely. The model-determined risk-based follow-up schedule detected the TLI earlier. The planning evaluation was refined because the model identified a better plan with a lower risk of TLI. Funding: The Sun Yat-sen University Clinical Research 5010 Program (2015020), Guangdong Basic and Applied Basic Research Foundation (2022A1515110356), Medical Scientific Research Foundation of Guangdong Province (A2022367), and Guangzhou Science and Technology Program (2023A04J1788).

15.
iScience ; 26(4): 106488, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37091229

RESUMO

Deficits in astrocyte function contribute to major depressive disorder (MDD) and suicide, but the therapeutic effect of directly reactivating astrocytes for depression remains unclear. Here, specific gains and losses of astrocytic cell functions in the medial prefrontal cortex (mPFC) bidirectionally regulate depression-like symptoms. Remarkably, recombinant human Thrombospondin-1 (rhTSP1), an astrocyte-secreted protein, exerted rapidly antidepressant-like actions through tyrosine hydroxylase (Th)/dopamine (DA)/dopamine D2 receptors (D2Rs) pathways, but not dopamine D1 receptors (D1Rs), which was dependent on SH3 and multiple ankyrin repeat domains 3 (Shank3) in the mPFC. TSP1 in the mPFC might have potential as a target for treating clinical depression.

16.
Anim Biotechnol ; 34(9): 4695-4702, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36897050

RESUMO

Increasing Cashmere production can add value because it is the primary product of Cashmere goats. Recent years, peoples find miRNAs are crucial in regulating the development of hair follicle. Following Solexa sequencing, many miRNAs were distinguishingly expressed in telogen skin samples of goats and sheep in earlier study. But the method through which miR-21 controls the growth of hair follicles is still ambiguous. Bioinformatics analysis was used to predict the target genes of miR-21. The mRNA level of miR-21 in telogen Cashmere goat skins was higher than in anagen, according to the results of qRT-PCR, and the target genes expressed similarly with miR-21. Western blot showed similar trend, the protein expression of FGF18 and SMAD7 were lower in anagen samples. The Dual-Luciferase reporter assay confirmed miRNA-21's relationship with its target gene, and the consequences indicated found FGF18 and SMAD7 have positive correlations with miR-21. Western blot and qRT-PCR distinguished the expression of protein and mRNA in miR-21 and its target genes. According to the consequence, we found that target genes expression was increased by miR-21 in HaCaT cells. This study identified that miR-21 might take part in the development of Cashmere goat's hair follicles by targeting FGF18 and SMAD7.


Assuntos
Folículo Piloso , MicroRNAs , Animais , Ovinos/genética , Folículo Piloso/metabolismo , Cabras , Perfilação da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/genética
17.
J Transl Med ; 21(1): 134, 2023 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-36814284

RESUMO

BACKGROUND: Radiotherapy resistance is the main cause of treatment failure in nasopharyngeal carcinoma (NPC), which leads to poor prognosis. It is urgent to elucidate the molecular mechanisms underlying radiotherapy resistance. METHODS: RNA-seq analysis was applied to five paired progressive disease (PD) and complete response (CR) NPC tissues. Loss-and gain-of-function assays were used for oncogenic function of FLI1 both in vitro and in vivo. RNA-seq analysis, ChIP assays and dual luciferase reporter assays were performed to explore the interaction between FLI1 and TIE1. Gene expression with clinical information from tissue microarray of NPC were analyzed for associations between FLI1/TIE1 expression and NPC prognosis. RESULTS: FLI1 is a potential radiosensitivity regulator which was dramatically overexpressed in the patients with PD to radiotherapy compared to those with CR. FLI1 induced radiotherapy resistance and enhanced the ability of DNA damage repair in vitro, and promoted radiotherapy resistance in vivo. Mechanistic investigations showed that FLI1 upregulated the transcription of TIE1 by binding to its promoter, thus activated the PI3K/AKT signaling pathway. A decrease in TIE1 expression restored radiosensitivity of NPC cells. Furthermore, NPC patients with high levels of FLI1 and TIE1 were correlated with poor prognosis. CONCLUSION: Our study has revealed that FLI1 regulates radiotherapy resistance of NPC through TIE1-mediated PI3K/AKT signaling pathway, suggesting that targeting the FLI1/TIE1 signaling pathway could be a potential therapeutic strategy to enhance the efficacy of radiotherapy in NPC.


Assuntos
Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Proteína Proto-Oncogênica c-fli-1 , Tolerância a Radiação , Receptor de TIE-1 , Humanos , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/radioterapia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Proteína Proto-Oncogênica c-fli-1/genética , Tolerância a Radiação/genética , Receptor de TIE-1/genética
18.
Turk Neurosurg ; 33(2): 199-207, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35652175

RESUMO

AIM: To perform an accurate primary repair of temporal bone defects. MATERIAL AND METHODS: The temporal bone defect models were performed in beagles. Extended estimated patches of the defects were predesigned by 3D reconstruction software and molded from polyether ether ketone (PEEK) using a lathe. The precise trimming of the extended PEEK patches was established via coordinate transformation of the patches between the navigation system and the reconstruction software, and in real-time tracing via intraoperative navigation. Trimmed PEEK patches were embedded onto the defects. Blood tests and image examinations were conducted postoperatively. RESULTS: The extended PEEK patches were prepared precisely according to the predesign. Real-time tracing of the actual skull defect profile was performed quickly and accurately. Trimmed skull patches perfectly matched the shape of the defects. No signs of infection, absorption, or translocation of the patches occurred postoperatively, and little epidural effusion was found. CONCLUSION: With the assistance of navigation and 3D reconstruction technology, customized molded PEEK patches can be used for accurate primary repair of temporal bone defects.


Assuntos
Polietilenoglicóis , Próteses e Implantes , Cães , Animais , Cetonas , Crânio/cirurgia
19.
Eur J Nucl Med Mol Imaging ; 50(3): 881-891, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36301324

RESUMO

PURPOSE: To compare PET/CT, MRI and ultrasonography in detecting recurrence of nasopharyngeal carcinoma and identify their benefit in staging, contouring and overall survival (OS). METHODS: Cohort A included 1453 patients with or without histopathology-confirmed local recurrence, while cohort B consisted of 316 patients with 606 histopathology-confirmed lymph nodes to compare the sensitivities and specificities of PET/CT, MRI and ultrasonography using McNemar test. Cohorts C and D consisted of 273 patients from cohort A and 267 patients from cohort B, respectively, to compare the distribution of PET/CT-based and MRI-based rT-stage and rN-stage and the accuracy of rN-stage using McNemar test. Cohort E included 30 random patients from cohort A to evaluate the changes in contouring with or without PET/CT by related-samples T test or Wilcoxon rank test. The OS of 61 rT3-4N0M0 patients staged by PET/CT plus MRI (cohort F) and 67 MRI-staged rT3-4N0M0 patients (cohort G) who underwent similar salvage treatment were compared by log-rank test and Cox regression. RESULTS: PET/CT had similar specificity to MRI but higher sensitivity (93.9% vs. 79.3%, P < 0.001) in detecting local recurrence. PET/CT, MRI and ultrasonography had comparable specificities, but PET/CT had greater sensitivity than MRI (90.9% vs. 67.6%, P < 0.001) and similar sensitivity to ultrasonography in diagnosing lymph nodes. According to PET/CT, more patients were staged rT3-4 (82.8% vs. 68.1%, P < 0.001) or rN + (89.9% vs. 69.3%, P < 0.001), and the rN-stage was more accurate (90.6% vs. 73.8%, P < 0.001). Accordingly, the contours of local recurrence were more precise (median Dice similarity coefficient 0.41 vs. 0.62, P < 0.001) when aided by PET/CT plus MRI. Patients staged by PET/CT plus MRI had a higher 3-year OS than patients staged by MRI alone (85.5% vs. 60.4%, P = 0.006; adjusted HR = 0.34, P = 0.005). CONCLUSION: PET/CT more accurately detected and staged recurrence of nasopharyngeal carcinoma and accordingly complemented MRI, providing benefit in contouring and OS.


Assuntos
Neoplasias Nasofaríngeas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Fluordesoxiglucose F18 , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/terapia , Terapia de Salvação , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/terapia , Recidiva Local de Neoplasia/patologia , Imageamento por Ressonância Magnética , Sensibilidade e Especificidade , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/terapia , Estadiamento de Neoplasias
20.
Int J Radiat Oncol Biol Phys ; 115(5): 1291-1300, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36462689

RESUMO

PURPOSE: We aimed to assess the value of dose distribution-based dosiomics and planning computed tomography-based radiomics to predict radiation-induced temporal lobe injury (TLI) and guide individualized intensity modulated radiation therapy. METHODS AND MATERIALS: A total of 5599 nasopharyngeal carcinoma patients were enrolled, including 2503, 1072, 988, and 1036 patients in the training, validation, prospective test, and external test cohorts, respectively. The concordance index (C-index) was used to compare the performance of the radiomics and dosiomics models with that of the quantitative analyses of normal tissue effects in the clinic and Wen's models. The predicted TLI-free survival rates of redesigned simulated plans with the same dose-volume histogram but different dose distributions for same patient in a cohort of 30 randomly selected patients were compared by the Wilcoxon matched-pairs signed-rank test. RESULTS: The radiomics and dosiomics signatures were constructed based on 30 selected computed tomography features and 10 selected dose distribution features, respectively, which were important predictors of TLI-free survival (all P <.001). However, the radiomics signature had a low C-index. The dosiomics risk model combining the dosiomics signature, D1cc, and age had favorable performance, with C-index values of 0.776, 0.811, 0.805, and 0.794 in the training, validation, prospective test, and external test cohorts, respectively, which were better than those of the quantitative analyses of normal tissue effects in the clinic model and Wen's model (all P <.001). The dosiomics risk model can further distinguish patients in a same risk category divided by other models (all P <.05). Conversely, the other models were unable to separate populations classified by the dosiomics risk model (all P > .05). Two simulated plans with the same dose-volume histogram but different dose distributions had different TLI-free survival rates predicted by dosiomics risk model (all P ≤ .002). CONCLUSIONS: The dosiomics risk model was superior to traditional models in predicting the risk of TLI. This is a promising approach to precisely predict radiation-induced toxicities and guide individualized intensity modulated radiation therapy.


Assuntos
Neoplasias Nasofaríngeas , Humanos , Estudos Prospectivos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/patologia , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia , Estudos Retrospectivos
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