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1.
Toxicol Appl Pharmacol ; : 116969, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38744347

RESUMO

Cysteine and glycine-rich protein 2 (CSRP2) is expressed differently in numerous cancers and plays a key role in carcinogenesis. However, the role of CSRP2 in glioma is unknown. This study sought to determine the expression profile and clinical significance of CSRP2 in glioma and explore its biological functions and mechanisms via lentivirus-mediated CSRP2 silencing experiments. Increased CSRP2 was frequently observed in gliomas, which was associated with clinicopathological characteristics and an unfavourable prognosis. Decreasing CSRP2 led to the suppression of malignant proliferation, metastasis and stemness in glioma cells while causing hypersensitivity to chemotherapeutic drugs. Mechanistic investigations revealed that CSRP2 plays a role in mediating the Notch signalling cascade. Silencing CSRP2 decreased the levels of Notch1, cleaved Notch1, HES1 and HEY1, suppressing the Notch signalling cascade. Reactivation of Notch markedly diminished the tumour-inhibiting effects of CSRP2 silencing on the malignant phenotypes of glioma cells. Notably, CSRP2-silencing glioma cells exhibited reduced potential in the formation of xenografts in nude mice in vivo, which was associated with an impaired Notch signalling cascade. These results showed that CSRP2 is overexpressed in glioma and has a crucial role in sustaining the malignant phenotypes of glioma, suggesting that targeting CSRP2 could be a promising strategy for glioma treatment.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38656317

RESUMO

CONTEXT: Precision medicine for pituitary neuroendocrine tumors (PitNETs) is limited by the lack of reliable research models. OBJECTIVE: To generate patient-derived organoids (PDOs), which could serve as a platform for personalized drug screening for PitNET patients. DESIGN: From July 2019 to May 2022, a total of 32 human PitNET specimens were collected for the establishment of organoids with an optimized culture protocol. SETTING: This study was conducted at Sun Yat-Sen University Cancer Center. PATIENTS: PitNET patients who were pathologically confirmed were enrolled in this study. INTERVENTIONS: Histological staining and whole-exome sequencing were utilized to confirm the pathologic and genomic features of PDOs. A drug response assay on PDOs was also performed. MAIN OUTCOME MEASURES: PDOs retained key genetic and morphological features of their parental tumors. RESULTS: PDOs were successfully established from various types of PitNET samples with an overall success rate of 87.5%. Clinical nonfunctioning PitNETs-derived organoids (22/23, 95.7%) showed a higher likelihood of successful generation compared to those from functioning PitNETs (6/9, 66.7%). Preservation of cellular structure, subtype-specific neuroendocrine profiles, mutational features, and tumor microenvironment heterogeneity from parental tumors was observed. A distinctive response profile in drug tests was observed among the organoids from patients with different subtypes of PitNETs. With the validation of key characteristics from parental tumors in histological, genomic, and microenvironment heterogeneity consistency assays, we demonstrated the predictive value of the PDOs in testing individual drugs. CONCLUSION: The established PDOs, retaining typical features of parental tumors, indicate a translational significance in innovating personalized treatment for refractory PitNETs.

3.
BMC Endocr Disord ; 24(1): 45, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622616

RESUMO

BACKGROUND: Headache is a common occurrence after endoscopic endonasal surgery (EES) for pituitary adenomas and significantly impacts the quality of life of patients. This study aims to investigate the effectiveness of nasal irrigation in relieving postoperative headache after EES. METHODS: A retrospective analysis was conducted on a cohort of 101 patients (Cohort I) who underwent EES for pituitary adenomas to explore the risk factors associated with postoperative headache. Another cohort of 72 patients (Cohort II) who received adjuvant nasal irrigation following surgery was enrolled for further analysis. The Headache Impact Test (HIT-6) was used to score the severity of headache, and patients with a HIT score > 55 were classified as having headache. RESULTS: In Cohort I, 21.78% of patients experienced headache one month after EES, which decreased to 5.94% at the three-month follow-up. Multivariate analysis revealed that postoperative nasal sinusitis (OR = 3.88, 95%CI 1.16-13.03, p = 0.028) and Hardy's grade C-D (OR = 10.53, 95%CI 1.02-109.19, p = 0.049) independently predicted the presence of postoperative headache at one month. At the three-month follow-up, patients with sinusitis had higher HIT-6 scores compared to those without sinusitis (44.43 ± 9.78 vs. 39.72 ± 5.25, p = 0.017). In Cohort II, the incidence of sinusitis at three months was significantly lower than that in Cohort I (p = 0.028). Importantly, both the incidence of headache and HIT-6 scores in Cohort II were significantly lower than those in Cohort I at the one- and three-month follow-ups. CONCLUSIONS: Postoperative sinusitis is an independent risk factor for the development of headache following EES for pituitary adenomas. Prophylactic nasal irrigation helps relieve postoperative headache, possibly by preventing the occurrence of sinusitis.


Assuntos
Neoplasias Hipofisárias , Sinusite , Humanos , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos , Qualidade de Vida , Resultado do Tratamento , Endoscopia/efeitos adversos , Cefaleia/etiologia , Cefaleia/prevenção & controle , Lavagem Nasal
4.
J Cell Mol Med ; 28(9): e18339, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38687049

RESUMO

Glioma is the most prevalent malignant brain tumour. Currently, reshaping its tumour microenvironment has emerged as an appealing strategy to enhance therapeutic efficacy. As the largest group of transmembrane transport proteins, solute carrier proteins (SLCs) are responsible for the transmembrane transport of various metabolites and ions. They play a crucial role in regulating the metabolism and functions of malignant cells and immune cells within the tumour microenvironment, making them a promising target in cancer therapy. Through multidimensional data analysis and experimental validation, we investigated the genetic landscape of SLCs in glioma. We established a classification system comprising 7-SLCs to predict the prognosis of glioma patients and their potential responses to immunotherapy and chemotherapy. Our findings unveiled specific SLC expression patterns and their correlation with the immune-suppressive microenvironment and metabolic status. The 7-SLC classification system was validated in distinguishing subgroups within the microenvironment, specifically identifying subsets involving malignant cells and tumour-associated macrophages. Furthermore, the orphan protein SLC43A3, a core member of the 7-SLC classification system, was identified as a key facilitator of tumour cell proliferation and migration, suggesting its potential as a novel target for cancer therapy.


Assuntos
Neoplasias Encefálicas , Regulação Neoplásica da Expressão Gênica , Glioma , Proteínas Carreadoras de Solutos , Microambiente Tumoral , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Humanos , Glioma/genética , Glioma/imunologia , Glioma/patologia , Glioma/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Proteínas Carreadoras de Solutos/genética , Proteínas Carreadoras de Solutos/metabolismo , Prognóstico , Proliferação de Células/genética , Perfilação da Expressão Gênica , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Multiômica
5.
World Neurosurg ; 184: e237-e246, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38272303

RESUMO

BACKGROUND: The use of cement in pedicle screw augmentation (PSA) enhances the pullout force of pedicle screws in vertebrae affected by osteoporosis. Risks involved in the use of cement for PSA include nerve injury and vascular damage caused by cement leakage. METHODS: This study included all patients who received PSA for degenerative lumbar stenosis in osteoporotic vertebrae from January 2014 to May 2022. Postoperative computed tomography was used to assess cement leakage. Correlation analysis and logistic regression analyses were used to establish the associated clinical or radiological factors, which were then used to construct nomograms and web calculators. RESULTS: The study comprised 181 patients including 886 screws inserted into 443 vertebrae. Perivertebral cement leakage was significantly associated with female sex, decreased bone mineral density, solid screws, and scattered cement distribution. Cement leakage through segmental veins (type S, 72.1%), leakage through basivertebral veins (type B, 23.9%), and instrument-related leakage (type I, 13.9%) accounted for most cement leakage. Patients with lower bone mineral density and scattered cement distribution were more likely to experience type S or type B leakage. Our analysis data showed that cement augmentation with cannulated and fenestrated screws tended toward concentrated cement distribution. Creation and verification of each nomogram additionally showcased the prognostic capability and medical significance of the corresponding model. CONCLUSIONS: Nomograms and web-based calculators can accurately forecast the probability of cement leakage. PSA should be routinely performed using cannulated and fenestrated screws, along with a moderate amount of high-viscosity cement, with continuous monitoring using fluoroscopy.


Assuntos
Parafusos Pediculares , Humanos , Feminino , Parafusos Pediculares/efeitos adversos , Nomogramas , Constrição Patológica , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Cimentos Ósseos/efeitos adversos
6.
WIREs Mech Dis ; 16(3): e1640, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38253964

RESUMO

Liver disease represents a significant global burden, placing individuals at a heightened risk of developing cirrhosis and liver cancer. Viral infections act as a primary cause of liver diseases on a worldwide scale. Infections involving hepatitis viruses, notably hepatitis B, C, and E viruses, stand out as the most prevalent contributors to acute and chronic intrahepatic adverse outcome, although the hepatitis C virus (HCV) can be effectively cured with antiviral drugs, but no preventative vaccination developed. Hepatitis B virus (HBV) and HCV can lead to both acute and chronic liver diseases, including liver cirrhosis and hepatocellular carcinoma (HCC), which are principal causes of worldwide morbidity and mortality. Other viruses, such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV), are capable of causing liver damage. Therefore, it is essential to recognize that virus infections and liver diseases are intricate and interconnected processes. A profound understanding of the underlying relationship between virus infections and liver diseases proves pivotal in the effective prevention, diagnosis, and treatment of these conditions. In this review, we delve into the mechanisms by which virus infections induce liver diseases, as well as explore the pathogenesis, diagnosis, and treatment of liver diseases. This article is categorized under: Infectious Diseases > Biomedical Engineering.


Assuntos
Hepatopatias , Humanos , Hepatopatias/virologia , Hepatopatias/diagnóstico , Hepatopatias/etiologia , Hepatopatias/terapia , Viroses/diagnóstico , Viroses/terapia , Viroses/virologia , Antivirais/uso terapêutico , Animais , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/etiologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/terapia
7.
J Orthop Surg Res ; 19(1): 32, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38178207

RESUMO

BACKGROUND: There are no reports discussing anatomic distribution of basivertebral foramen (BVF) in the osteoporotic vertebral body, which is critical in the analysis of the risk of epidural cement leakage (ECL) after cement-augmented pedicle screw fixation (CAPSF). METHODS: 371 osteoporotic patients using 1898 cement-augmented screws were included. Preoperative computed tomography (CT) was used to determine the frequency, width, height, and depth of magistral BVF in T10~L5. Additionally, we measured the distance between BVF and the left/right borders of vertebral body as well as the distance between BVF and upper/lower endplates. Following CAPSF, the severity of ECL and the position of pedicle screws were determined by postoperative CT. Finally, significant risk factors for extensive ECL were identified through binary logistic regression analysis. RESULTS: Of 2968 vertebral bodies ranging from T10 to L5, 801 (42.2%) had a magistral BVF. From T10 to L5, the frequency of magistral BVF appeared to gradually increase. The magistral BVF was much closer to the upper endplate and the depth accounted for about a quarter of anteroposterior diameter of vertebral body. Overall, there were 19 patients (5.1%) and 32 screws (1.7%) with extensive ECL, nine of whom had neurological symptoms. The independent risk factors for extensive ECL were the magistral BVF (OR = 8.62, P < 0.001), more volume of cement injected (OR = 1.57, P = 0.031), reduced distance from screw tip to vertebral midline (OR = 0.76, P = 0.003) and vertebral posterior wall (OR = 0.77, P < 0.001) respectively. CONCLUSION: When planning a CAPSF procedure, it is important to consider anatomical distribution of BVF and improve screw implantation methods.


Assuntos
Cimentos Ósseos , Parafusos Pediculares , Humanos , Cimentos Ósseos/efeitos adversos , Parafusos Pediculares/efeitos adversos , Corpo Vertebral , Relevância Clínica , Estudos de Casos e Controles , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia
8.
Genet Test Mol Biomarkers ; 28(1): 22-32, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38294358

RESUMO

Purpose: Recently, apoptosis-related genes were shown to modulate cancer immunity. However, the role of apoptosis-related genes in the glioma immune microenvironment (GIME) remains unknown. This study aimed to explore the prognostic value of apoptosis-related genes in glioma. Methods: Doxorubicin was used to induce glioma cell apoptosis, and four differentially expressed apoptosis-related genes were identified: CREM, TNFSF12, PEA15, and PRKCD. Kaplan-Meier analyses, receiver operating characteristic curve analyses, and nomograms were established to determine the relationship between risk markers and the prognosis of patients with glioma. Results: Risk biomarkers were significantly associated with overall survival, immune cell infiltration, and immune checkpoints in patients with glioma. Somatic mutations and anti-PD-1/L1 immunotherapy were associated with worse prognosis in the high-risk group receiving anti-PD-1/L1 therapy. The expression of these four apoptosis-related genes was verified using quantitative polymerase chain reaction and immunohistochemistry, and the relationship between these four genes and apoptosis was examined using flow cytometry. Conclusions: This study suggests that apoptosis-related genes play a critical role in shaping the GIME. Assessing the apoptotic patterns of individual tumors will enhance our understanding of GIME infiltration features and lead to improved strategies for immunotherapy.


Assuntos
Glioma , Humanos , Prognóstico , Glioma/genética , Apoptose/genética , Doxorrubicina , Citometria de Fluxo , Microambiente Tumoral/genética , Proteínas Reguladoras de Apoptose
9.
Orthop Surg ; 16(2): 420-428, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38191985

RESUMO

OBJECTIVE: Foraminoplasty is an important step in transforaminal endoscopic lumbar discectomy (TELD). A trephine is widely used in foraminoplasty. However, foraminoplasty using a trephine alone sometimes fails to remove the resected bone, resulting in the bone remaining in the foramen or spinal canal, which can potentially cause neurological irritation or injury. The objective of this study is to introduce a self-designed tool, referred to as an anchoring drill, for use with a trephine in foraminoplasty in TELD and to evaluate its advantages. METHODS: A retrospective review was performed to identify patients who underwent L4-5 TELD between January 2019 to January 2022. Foraminoplasty was performed in all patients. Depending on whether the anchoring drill was used or not, patients were divided into two groups. Surgery-related parameters and complications were reviewed. Visual analog scale (VAS) and Japanese Orthopaedic Association (JOA) scores were also assessed for all patients. SPSS statistical software was used for statistical calculation. RESULTS: A total of 100 patients were included (55 in the anchoring drill group and 45 in the trephine group). The incidence of residual bone fragments after foraminoplasty of the anchoring drill group was 9.09%, which was lower than that of the trephine group, at 33.33% (p < 0.05). The mean endoscopic operation time of the anchoring drill group was shorter than that of the trephine group (p < 0.05). The mean fluoroscopy time and duration of foraminoplasty showed no significant differences between the two cohorts. The total perioperative complication incidence was lower in the anchoring drill group, in which the neural irritation incidence showed a significant difference (anchoring drill group: 3.64%, trephine group: 17.78%, p < 0.05). VAS and JOA scores were significantly improved after the operation for all patients (p < 0.001), however, no statistical differences were found between the two groups at each follow-up visit. CONCLUSION: The combination of a trephine with an anchor drill was demonstrated to be safe and effective in foraminoplasty in TELD, improving the success rate of foraminoplasty and reducing neurological complications compared to using trephine alone.


Assuntos
Discotomia Percutânea , Deslocamento do Disco Intervertebral , Humanos , Estudos Retrospectivos , Deslocamento do Disco Intervertebral/cirurgia , Resultado do Tratamento , Vértebras Lombares/cirurgia , Endoscopia/métodos , Discotomia/métodos , Discotomia Percutânea/métodos
10.
Arch Orthop Trauma Surg ; 144(3): 1013-1020, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38078951

RESUMO

INTRODUCTION: In cement-augmented pedicle screw fixation (CAPSF), epidural cement leakage (CL) is a frequently reported complication with the potential for neural injury, especially when it is extensive. To date, there has been no reports discussing basivertebral foramen morphology and pedicle screw placement, which is critical in the analysis of the risk of extensive epidural CL. Thus, this study aimed to identify the incidence and risk factors for extensive epidural CL in osteoporotic patients with CAPSF. MATERIALS AND METHODS: 371 osteoporotic patients using 1898 cement-augmented screws were included. Preoperative computed tomography (CT) was utilized to characterize basivertebral foramen morphology. Following CAPSF, the severity of epidural CL, the implantation position of pedicle screw and cement extension within the vertebral body were determined by postoperative CT. In this study, significant risk factors for extensive epidural CL were identified through logistic regression analysis. RESULTS: There were 19 patients (5.1%) and 32 screws (1.7%) with extensive epidural CL. Nine patients (involving 19 screws) had neurological symptoms. The independent risk factors for patients with extensive epidural CL were decreased BMD and increased number of augmented screws. Significant predictors for extensive epidural CL were a magistral type of basivertebral foramen, more volume of cement injected, solid screw, a shallower screw implantation, and the smaller distance between the tip of the screw and the midline of vertebral body. CONCLUSION: Extensive epidural CL risk was significant in CAPSF when a magistral basivertebral foramen was present; solid screws and more volume of cement were used; and screw tip was implanted shallower or closer to the midline.


Assuntos
Cimentos Ósseos , Parafusos Pediculares , Humanos , Cimentos Ósseos/efeitos adversos , Parafusos Pediculares/efeitos adversos , Estudos Retrospectivos , Incidência , Fatores de Risco , Vértebras Lombares/cirurgia
11.
Eur Radiol ; 34(4): 2468-2479, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37812296

RESUMO

OBJECTIVE: The purpose of this study was to develop and validate a nomogram combined multiparametric MRI and clinical indicators for identifying the WHO grade of meningioma. MATERIALS AND METHODS: Five hundred and sixty-eight patients were included in this study, who were diagnosed pathologically as having meningiomas. Firstly, radiomics features were extracted from CE-T1, T2, and 1-cm-thick tumor-to-brain interface (BTI) images. Then, difference analysis and the least absolute shrinkage and selection operator were orderly used to select the most representative features. Next, the support vector machine algorithm was conducted to predict the WHO grade of meningioma. Furthermore, a nomogram incorporated radiomics features and valuable clinical indicators was constructed by logistic regression. The performance of the nomogram was assessed by calibration and clinical effectiveness, as well as internal validation. RESULTS: Peritumoral edema volume and gender are independent risk factors for predicting meningioma grade. The multiparametric MRI features incorporating CE-T1, T2, and BTI features showed the higher performance for prediction of meningioma grade with a pooled AUC = 0.885 (95% CI, 0.821-0.946) and 0.860 (95% CI, 0.788-0.923) in the training and test groups, respectively. Then, a nomogram with a pooled AUC = 0.912 (95% CI, 0.876-0.961), combined radiomics score, peritumoral edema volume, and gender improved diagnostic performance compared to radiomics model or clinical model and showed good calibration as the true results. Moreover, decision curve analysis demonstrated satisfactory clinical effectiveness of the proposed nomogram. CONCLUSIONS: A novel nomogram is simple yet effective in differentiating WHO grades of meningioma and thus can be used in patients with meningiomas. CLINICAL RELEVANCE STATEMENT: We proposed a nomogram that included clinical indicators and multi-parameter radiomics features, which can accurately, objectively, and non-invasively differentiate WHO grading of meningioma and thus can be used in clinical work. KEY POINTS: • The study combined radiomics features and clinical indicators for objectively predicting the meningioma grade. • The model with CE-T1 + T2 + brain-to-tumor interface features demonstrated the best predictive performance by investigating seven different radiomics models. • The nomogram potentially has clinical applications in distinguishing high-grade and low-grade meningiomas.


Assuntos
Neoplasias Encefálicas , Neoplasias Meníngeas , Meningioma , Imageamento por Ressonância Magnética Multiparamétrica , Humanos , Meningioma/diagnóstico por imagem , Estudos Retrospectivos , Nomogramas , Neoplasias Meníngeas/diagnóstico por imagem , Aprendizado de Máquina , Edema , Organização Mundial da Saúde
12.
World Neurosurg ; 183: e261-e267, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38159603

RESUMO

OBJECTIVE: To examine the association between vertebral cancellous Hounsfield units (HUs), age, bone mineral density, and T-score in a sample of Chinese adults. METHODS: The study included a sample of 739 participants. Age, bone mineral density, and T-score of each participant were recorded, and HUs were measured in the L1-L4 vertebrae. RESULTS: Data analysis revealed that HUs of vertebral cancellous bone across the pedicle level decreased with age, with women having higher values than men up to age 50 and vice versa thereafter. Furthermore, a positive correlation was found between HUs of vertebral cancellous bone across the pedicle level and bone mineral density/T-score in the L1-L4 vertebrae, but with a weaker correlation in the L4 vertebrae. Additionally, HU values for participants with osteoporosis were significantly lower than HU values for participants with osteopenia and normal bone health. CONCLUSIONS: From the findings of this study, it can be concluded that HUs may be a potential predictor of bone health, with implications for presurgical assessment of the quality of bone-screw interfaces for spinal surgery.


Assuntos
Doenças Ósseas Metabólicas , Osteoporose , Adulto , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Densidade Óssea , Tomografia Computadorizada por Raios X , Osteoporose/diagnóstico por imagem , Doenças Ósseas Metabólicas/diagnóstico por imagem , Doenças Ósseas Metabólicas/epidemiologia , Vértebras Lombares/diagnóstico por imagem , China , Estudos Retrospectivos , Absorciometria de Fóton
13.
Health Inf Sci Syst ; 11(1): 58, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38028959

RESUMO

As medical treatments continue to advance rapidly, minimally invasive surgery (MIS) has found extensive applications across various clinical procedures. Accurate identification of medical instruments plays a vital role in comprehending surgical situations and facilitating endoscopic image-guided surgical procedures. However, the endoscopic instrument detection poses a great challenge owing to the narrow operating space, with various interfering factors (e.g. smoke, blood, body fluids) and inevitable issues (e.g. mirror reflection, visual obstruction, illumination variation) in the surgery. To promote surgical efficiency and safety in MIS, this paper proposes a cross-layer aggregated attention detection network (CLAD-Net) for accurate and real-time detection of endoscopic instruments in complex surgical scenarios. We propose a cross-layer aggregation attention module to enhance the fusion of features and raise the effectiveness of lateral propagation of feature information. We propose a composite attention mechanism (CAM) to extract contextual information at different scales and model the importance of each channel in the feature map, mitigate the information loss due to feature fusion, and effectively solve the problem of inconsistent target size and low contrast in complex contexts. Moreover, the proposed feature refinement module (RM) enhances the network's ability to extract target edge and detail information by adaptively adjusting the feature weights to fuse different layers of features. The performance of CLAD-Net was evaluated using a public laparoscopic dataset Cholec80 and another set of neuroendoscopic dataset from Sun Yat-sen University Cancer Center. From both datasets and comparisons, CLAD-Net achieves the AP0.5 of 98.9% and 98.6%, respectively, that is better than advanced detection networks. A video for the real-time detection is presented in the following link: https://github.com/A0268/video-demo.

14.
J Hematol Oncol ; 16(1): 115, 2023 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-38031188

RESUMO

BACKGROUND: T cell engagers (TCEs) have been established as an emerging modality for hematologic malignancies, but solid tumors remain refractory. However, the upregulation of programmed cell death 1 (PD-1) is correlated with T cell dysfunction that confer tumor-mediated immunosuppression. Developing a novel nanobody-based trispecific T cell engager (Nb-TriTE) would be a potential strategy to improve therapeutic efficacy. METHODS: Given the therapeutic potential of nanobodies (Nbs), we first screened Nb targeting fibroblast activation protein (FAP) and successfully generated a Nb-based bispecific T cell engager (Nb-BiTE) targeting FAP. Then, we developed a Nb-TriTE by fusing an anti-PD-1 Nb to the Nb-BiTE. The biological activity and antitumor efficacy of the Nb-TriTE were evaluated in vitro and in both cell line-derived and patient-derived xenograft mouse models. RESULTS: We had for the first time successfully selected a FAP Nb for the generation of novel Nb-BiTE and Nb-TriTE, which showed good binding ability to their targets. Nb-TriTE not only induced robust tumor antigen-specific killing, potent T cell activation and enhanced T cell function in vitro, but also suppressed tumor growth, improved survival and mediated more T cell infiltration than Nb-BiTE in mouse models of different solid tumors without toxicity. CONCLUSIONS: This novel Nb-TriTE provides a promising and universal platform to overcome tumor-mediated immunosuppression and improve patient outcomes in the future.


Assuntos
Anticorpos Biespecíficos , Neoplasias , Humanos , Camundongos , Animais , Nióbio/metabolismo , Neoplasias/terapia , Terapia de Imunossupressão , Linfócitos T , Tolerância Imunológica , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Biespecíficos/metabolismo
15.
Int J Mol Sci ; 24(18)2023 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-37762224

RESUMO

POLD4 plays a crucial part in the complex machinery of DNA replication and repair as a vital component of the DNA polymerase delta complex. In this research, we obtained original information from various publicly available databases. Using a blend of R programming and internet resources, we initiated an extensive examination into the correlation between POLD4 expression and the various elements of cancers. In addition, we performed knockdown experiments in glioma cell lines to authenticate its significant impact. We discovered that POLD4 is upregulated in various malignant tumors, demonstrating a significant correlation with poor patient survival prognosis. Using function analysis, it was uncovered that POLD4 exhibited intricate associations with signaling pathways spanning multiple tumor types. Subsequent investigations unveiled the close association of POLD4 with the immune microenvironment and the effectiveness of immunotherapy. Drugs like trametinib, saracatinib, and dasatinib may be used in patients with high POLD4. Using experimental analysis, we further confirmed the overexpression of POLD4 in gliomas, as well as its correlation with glioma recurrence, proliferation, and the suppressive immune microenvironment. Our research findings indicate that the expression pattern of POLD4 not only serves as a robust indicator of prognosis in cancer patients but also holds promising potential as a new focus for treatment.


Assuntos
DNA Polimerase III , Glioma , Humanos , Linhagem Celular , Proliferação de Células , Replicação do DNA , Glioma/genética , Microambiente Tumoral/genética
17.
Orthop Surg ; 15(9): 2274-2282, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37403557

RESUMO

OBJECTS: Oblique lumbar interbody fusion (OLIF) has gained increasing popularity recently. However, complications resulting from intraoperative retraction of psoas major (PM) sometimes occur. The aim of this study is to evaluate the degree of PM swelling by developing a scoring system called the Psoas Major Swelling Grade (PMSG), and to investigate the correlation between the PMSG and clinical outcomes after OLIF. METHODS: Patients who underwent L4-5 OLIF at our hospital from May 2019 to May 2021 were reviewed and all data were recorded. The extent of postoperative PM swelling was determined by calculating the percentage of change in the PM area before and after surgery on MRI and divided into three grades subsequently. Swelling within the range of 0% to 25% was defined as grade I, 25%-50% was grade II, and more than 50% was grade III. All patients were grouped into the new grade system and followed up for at least 1 year, during which the visual analog scale (VAS) and Oswestry disability index (ODI) scores were recorded. Categorical data were analyzed using chi-square and Fisher's exact tests, while continuous variables were assessed with one-way ANOVA and paired t-tests. RESULTS: Eighty-nine consecutive patients were enrolled in this study, with a mean follow-up duration of 16.9 months. The proportion of female patients in the PMSG I, II, and III groups was 57.1%, 58.3%, and 84.1%, respectively (p = 0.024).  Furthermore, the total complication rate was 43.2% in the PMSG III group, significantly higher than 9.5% and 20.8% in the PMSG I and II groups (p = 0.012). The incidence of thigh paraesthesia was also considerably higher in the PMSG III group at 34.1% (p = 0.015), compared to 9.5% and 8.3% in the PMSG I and II groups. Among the patients, 12.4% exhibited a teardrop-shaped PM, with the majority (90.9%) belonging to the PMSG III group (p = 0.012). Additionally, the PMSG III group demonstrated a higher estimated blood loss (p = 0.007) and significantly worse clinical scores at the 1-week follow-up assessment (p < 0.001). CONCLUSION: PM swelling adversely affects the OLIF prognosis. Female patients with teardrop-shaped PM are more likely to develop swelling after OLIF. A higher PMSG is associated with a higher complication rate of thigh pain or numbness and worse short-term clinical outcomes.


Assuntos
Vértebras Lombares , Fusão Vertebral , Humanos , Feminino , Estudos Retrospectivos , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Região Lombossacral/cirurgia , Dor , Resultado do Tratamento
18.
Orthop Surg ; 15(10): 2730-2735, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37435856

RESUMO

BACKGROUND: Lateral displacement of cage is a rarely seen complication of oblique lumbar interbody fusion (OLIF). To the best of our knowledge, this complication has always been revised with posterior open surgery. However, open surgery often associates with large trauma and long period of recovery. CASE PRESENTATION: In the case presented, a 64-year-old male patient with lateral displacement of cage which consequently caused neurological symptoms after OLIF, was reported and surgically revised with an endoscopic resection and decompression technique. The surgery was performed through a posterolateral approach which was similar to transforaminal approach, with estimated blood loss of 45mL and whole operation time of 70 min. Neurological symptoms were disappeared after operation immediately and the patient was discharged 2 days later. He reported no symptoms other than mild weakness of the lower back at the last follow-up of 12 months. CONCLUSION: Endoscopic decompression technique may be an effective alternative to surgically treat lateral displacement of cage after OLIF with advantages of minimal invasion and quick recovery.

19.
Clin Transl Sci ; 16(10): 1957-1971, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37503932

RESUMO

Ferroptosis is an iron-dependent cell death process mainly triggered by reactive oxygen species (ROS) and lipid peroxidation. Thioredoxin domain protein 12 (TXNDC12) promotes the development of some tumors; however, its function in tumor ferroptosis remains unclear. In this study, we found that knockdown of TXNDC12 promoted erastin-induced increase in ROS, lipid peroxidation, and Fe2+ levels, and decreased glutathione content. TXNDC12 is involved in ferroptosis by regulating SLC7A11. Further studies showed that TXNDC12 knockdown promoted an erastin-induced decrease in glioma cell viability. Overall, TXNDC12 played a significant role in ferroptosis by modulating SLC7A11 expression. Thus, TXNDC12 and ferroptosis may provide new targets for the treatment of gliomas.


Assuntos
Ferroptose , Glioma , Proteína Dissulfeto Redutase (Glutationa) , Humanos , Ferroptose/genética , Espécies Reativas de Oxigênio/metabolismo , Morte Celular , Ferro/metabolismo , Glioma/genética , Proteína Dissulfeto Redutase (Glutationa)/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Sistema y+ de Transporte de Aminoácidos/metabolismo
20.
J Mol Neurosci ; 73(7-8): 608-627, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37488455

RESUMO

Inflammatory response plays a crucial role in the development and progression of gliomas. Whereas the prognostic esteem of inflammatory response-related genes has never been comprehensively explored in glioma, the RNA-seq information and clinical data of patients with glioma were extracted from TCGA, CGGA, and Rembrandt databases. The differentially expressed genes (DEGs) were picked out between glioma tissue and non-tumor brain tissue (NBT). Then, the least absolute shrinkage and selection operator (LASSO) regression analysis was performed to construct the prognostic signature in the TCGA cohort and verified in other cohorts. Kaplan-Meier survival analyses were conducted to compare the overall survival (OS) between the high and low-risk groups. Univariate and multivariate Cox analyses were subsequently used to confirm the independent prognostic factors of OS, and then, the nomogram was established based them. Furthermore, immune infiltration, immune checkpoints, and immunotherapy were also probed and compared between high and low-risk groups. The four genes were also analyzed by qRT-PCR, immunohistochemistry, and western blot trials between glioma tissue and NBT. The 39 DEGs were identified between glioma tissue and NBT, of which 31 genes are associated to the prognosis of glioma. The 8 optimal inflammatory response-related genes were selected to construct the prognostic inflammatory response-related signature (IRRS) through the LASSO regression. The effectiveness of the IRRS was verified in the TCGA, CGGA, and Rembrandt cohorts. Meanwhile, a nomogram with better accuracy was established to predict OS based on the independent prognostic factors. The IRRS was highly correlated with clinicopathological features, immune infiltration, and genomic alterations in glioma patients. In addition, four selective genes also verified the difference between glioma tissue and NBT. A novel prognostic signature was associated with the prognosis, immune infiltration, and immunotherapy effect in patients with gliomas. Thus, this study could provide a perspective for glioma prognosis and treatment.


Assuntos
Glioma , Humanos , Glioma/genética , Glioma/terapia , Imunoterapia , Encéfalo , Western Blotting , Bases de Dados Factuais
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