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1.
Mod Rheumatol ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38813667

RESUMO

OBJECTIVES: To compare the lumbar posterior lesions between axial spondyloarthritis (axSpA) and lumbar disc herniation (LDH) patients, then their diagnostic value and related factors were evaluated. METHODS: This cross-sectional study included axSpA patients from January 2020 to September 2023. They were classified as ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA) individuals. Canada-Denmark (CANDEN) magnetic resonance imaging (MRI) scoring system was used to assess the defects of the lumbar spine. Receiver operating characteristic curve analysis was utilized to determine the value of distinguishing nr-axSpA. Linear regression analyses were adopted to find the relevant factors for lumbar posterior lesions. RESULTS: Ninety-six AS, 98 nr-axSpA, and 108 LDH patients were included. The CANDEN scores were greater in axSpA patients, AS in particular. Furthermore, lumbar posterior lesions can distinguish AS, nr-axSpA, and LDH. Besides, lumbar posterior lesions were positively related to the similar MRI changes in their adjacent structures, but were inversely associated with the other abnormalities. CONCLUSIONS: Lumbar posterior lesions were more serious in axSpA patients. These alterations had value in distinguishing axSpA. Lumbar posterior defects were related to their adjacent components, and they may not fully follow the MRI changing pattern of vertebral bodies and sacroiliac joints.

2.
Br J Cancer ; 128(7): 1320-1332, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36703078

RESUMO

BACKGROUND: We aimed to develop and validate a plasma extracellular vesicle circular RNA (circRNA)-based signature that can predict overall survival (OS) in first-line abiraterone therapy for metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: In total, 582 mCRPC patients undergoing first-line abiraterone therapy from four institutions were sorted by three phases. In the discovery phase, 30 plasma samples from 30 case-matched patients with or without early progression were obtained to generate circRNA expression profiles using RNA sequencing. In the training phase, differentially expressed circRNAs were examined using digital droplet PCR in a training cohort (n = 203). The circRNA signature was constructed using a least absolute shrinkage and selection operator Cox regression to predict OS. In the validation phase, the prognostic ability of this signature was prospectively validated in two external cohorts (Cohort I, n = 183; Cohort II, n = 166). RESULTS: We developed a five-circRNA signature, based on circCEP112, circFAM13A, circBRWD1, circVPS13C and circMACROD2, which successfully stratified patients into high-risk and low-risk groups. The prognostic ability of this signature was prospectively validated in two external cohorts (P < 0.0001, P < 0.0001). Patients with high-risk scores had shorter OS than patients with low-risk scores. CONCLUSION: This five-circRNA signature is a reliable predictor of OS for mCRPC patients undergoing abiraterone.


Assuntos
Neoplasias de Próstata Resistentes à Castração , RNA Circular , Masculino , Humanos , RNA Circular/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Antígeno Prostático Específico , Resultado do Tratamento , Acetato de Abiraterona/efeitos adversos
3.
Eur Arch Otorhinolaryngol ; 280(5): 2479-2488, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36577788

RESUMO

OBJECTIVES: First, we retrospectively compared the clinical efficacy of concurrent chemoradiotherapy combined with nimotuzumab vs. chemoradiotherapy alone in patients with nasopharyngeal carcinoma (NPC) and cervical lymph node metastasis. Second, we analyzed the value of Ki-67 as a predictor of nimotuzumab efficacy. METHODS: From January 2012 to December 2019, 1250 patients with cervical lymph node metastasis eligible for enrollment were included, of whom 383 were treated with concurrent chemoradiotherapy combined with nimotuzumab (targeted therapy group), and 867 were treated with concurrent chemoradiotherapy (CRT group). A total of 381 pairs of patients were matched using 1:1 propensity score matching, and differences in clinical prognosis were compared between the two groups. RESULTS: Overall survival (OS) (P = 0.028), disease-free survival (DFS) (P = 0.040), and distant metastasis-free survival (DMFS) (P = 0.040) were better in the targeted therapy compared to the CRT group. Multivariate analysis revealed that clinical staging, chemotherapy, and nimotuzumab therapy were predictors of OS and DFS. In the targeted therapy group, patients with ≥ 50% Ki-67 positivity had better OS and DFS rates than those with < 50% Ki-67 positivity. CONCLUSIONS: In patients with stage N1-3 NPC and lymph node metastasis, the addition of nimotuzumab to concurrent chemoradiotherapy may provide additional survival benefits. Ki-67 is a potential biomarker with clinical predictive value for the efficacy of nimotuzumab combined with chemoradiotherapy.


Assuntos
Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Metástase Linfática , Estudos Retrospectivos , Antígeno Ki-67 , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Estadiamento de Neoplasias
4.
Sensors (Basel) ; 23(15)2023 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-37571767

RESUMO

Due to their ability to achieve higher DOA estimation accuracy and larger degrees of freedom (DOF) using a fixed number of antennas, sparse arrays, etc., nested and coprime arrays have attracted a lot of attention in relation to research into direction of arrival (DOA) estimation. However, the usage of the sparse array is based on the assumption that the signals are independent of each other, which is hard to guarantee in practice due to the complex propagation environment. To address the challenge of sparse arrays struggling to handle coherent wideband signals, we propose the following method. Firstly, we exploit the coherent signal subspace method (CSSM) to focus the wideband signals on the reference frequency and assist in the decorrelation process, which can be implemented without any pre-estimations. Then, we virtualize the covariance matrix of sparse array due to the decorrelation operation. Next, an enhanced spatial smoothing algorithm is applied to make full use of the information available in the data covariance matrix, as well as to improve the decorrelation effect, after which stage the multiple signal classification (MUSIC) algorithm is used to obtain DOA estimations. In the simulation, with reference to the root mean square error (RMSE) that varies in tandem with the signal-to-noise ratio (SNR), the algorithm achieves satisfactory results compared to other state-of-the-art algorithms, including sparse arrays using the traditional incoherent signal subspace method (ISSM), the coherent signal subspace method (CSSM), spatial smoothing algorithms, etc. Furthermore, the proposed method is also validated via real data tests, and the error value is only 0.2 degrees in real data tests, which is lower than those of the other methods in real data tests.

5.
Sensors (Basel) ; 23(14)2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37514657

RESUMO

In an ultra-wideband (UWB) system, the two-dimensional (2D) multiple signal classification (MUSIC) algorithms based on high-precision 2D spectral peak search can jointly estimate the time of arrival (TOA) and angle of arrival (AOA). However, the computational complexity of 2D-MUSIC is very high, and the corresponding data model is only based on the dual antennas. To solve these problems, a low-complexity algorithm for joint AOA and TOA estimation of the multipath ultra-wideband signal is proposed. Firstly, the dual antenna sensing data model is extended to the antenna array case. Then, based on the array-sensing data model, the proposed algorithm transforms the 2D spectral peak search of 2D-MUSIC into a secondary optimization problem to extract the estimation of AOA via only 1D search. Finally, the acquired AOA estimations are brought back, and the TOA estimations are also obtained through a 1D search. Moreover, in the case of an unknown transmitted signal waveform, the proposed method can still distinguish the main path signal based on the time difference of arrival of different paths, which shows wider applications. The simulation results show that the proposed algorithm outperforms the Root-MUSIC algorithm and the estimation of signal parameters using the rotational invariance techniques (ESPRIT) algorithm, and keeps the same estimation accuracy but with greatly reduced computational complexity compared to the 2D-MUSIC algorithm.

6.
Mod Rheumatol ; 32(5): 974-979, 2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34918121

RESUMO

OBJECTIVES: The study aims to investigate the clinical significance of platelet to albumin ratio (PAR), neutrophil to albumin ratio (NAR), and monocyte to albumin ratio (MAR) in axial spondyloarthritis (axSpA). METHODS: Two hundred and ninety-seven axSpA patients and 71 healthy volunteers were recruited. AxSpA patients were divided into inactive group and active group. Spearman's correlation, receiver operating characteristic (ROC) curves, and binary logistic regression analysis were conducted. RESULTS: Albumin was lower in axSpA group, while neutrophil, platelet, monocyte, NAR, PAR, and MAR were higher (p < .05). Albumin was negatively correlated with BASDAI and BASFI (p < .05). Platelet, NAR, PAR, MAR, ESR, and CRP were all positively correlated with BASDAI and BASFI (p < .05). Albumin was lower in axSpA of active group, while platelet, NAR, PAR, MAR, ESR, and CRP were higher (p < .05). ROC curve indicated that the AUC of PAR for axSpA of active group was higher than that of other variables. The optimal cut-off value of PAR was 6.354, with Youden index of 0.337, specificity of 55.4%, and sensitivity of 78.4%. Logistic regression analysis result suggested that PAR was an independent indicator for axSpA disease activity. CONCLUSIONS: PAR had a high diagnostic value for axSpA of active group. PAR was a novel and reliable indicator for axSpA disease activity.


Assuntos
Espondiloartrite Axial , Espondilartrite , Espondilite Anquilosante , Albuminas , Plaquetas , Humanos , Curva ROC , Espondilartrite/diagnóstico , Espondilite Anquilosante/diagnóstico
7.
Mol Cancer ; 20(1): 96, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301266

RESUMO

The aim of this study was to identify a urine extracellular vesicle circular RNA (circRNA) classifier that could detect high-grade prostate cancer (PCa) of Grade Group (GG) 2 or greater. For this purpose, we used RNA sequencing to identify candidate circRNAs from urinary extracellular vesicles from 11 patients with high-grade PCa and 11 case-matched patients with benign prostatic hyperplasia. Using ddPCR in a training cohort (n = 263), we built a urine extracellular vesicle circRNA classifier (Ccirc, containing circPDLIM5, circSCAF8, circPLXDC2, circSCAMP1, and circCCNT2), which was evaluated in two independent cohorts (n = 497, n = 505). Ccirc showed higher accuracy than two standard of care risk calculators (RCs) (PCPT-RC 2.0 and ERSPC-RC) in both the training cohort and the validation cohorts. In all three cohorts, this novel urine extracellular vesicle circRNA classifier plus RCs was statistically more predictive than RCs alone for predicting ≥ GG2 PCa. This assay, which does not require precollection digital rectal examination nor special handling, is repeatable, noninvasive, and can be easily implemented as part of the basic clinical workflow.


Assuntos
Biomarcadores Tumorais , Ácidos Nucleicos Livres , Vesículas Extracelulares/metabolismo , Antígeno Prostático Específico/urina , Neoplasias da Próstata/genética , Neoplasias da Próstata/urina , RNA Circular/genética , Biópsia , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Gradação de Tumores , Prognóstico , Neoplasias da Próstata/diagnóstico , RNA Circular/metabolismo , Curva ROC , Reprodutibilidade dos Testes
8.
Environ Res ; 186: 109479, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32339955

RESUMO

In a lake basin, there is a mismatch between river and lake water quality targets and a method for setting specific water quality targets for these rivers is urgently needed. Using Dianchi Lake as an example, we proposed a lake basin water quality management system based on the river-lake water quality response relationship, coupled with a Soil and Water Assessment Tool (SWAT) basin hydrological model and Environmental Fluid Dynamics Code (EFDC) lake water quality hydrodynamic model. River water quality control requirements based on the river-lake water quality response were proposed, under the premise that the Dianchi Lake water quality reaches the required standard. Then, water quality control targets for rivers were determined, and corrected for influencing factors, such as current river water quality and composition of flow. Our systematic approach efficiently identified key lake basin pollution sources, and accurately located key points for water quality improvement and pollution control. Combined with a correction for clean water source and current water quality of each river, the proposed water quality targets were practical and operable. Meanwhile, the EFDC model was used to verify the entire process to ensure that river water quality targets could be set to achieve lake water quality targets. To ensure that Dianchi Lake water quality can reach Class IV standard, the Chemical oxygen demand (COD) concentration would need to be maintained under 30 mg/L,Waihai total nitrogen (TN) below 7 mg/L, total phosphorus (TP) below 0.2 mg/L, and ammonia nitrogen (NH3-N) below 2 mg/L.


Assuntos
Rios , Poluentes Químicos da Água , China , Monitoramento Ambiental , Lagos , Nitrogênio/análise , Fósforo/análise , Poluentes Químicos da Água/análise , Qualidade da Água
10.
Biochem Biophys Res Commun ; 459(3): 416-23, 2015 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-25744029

RESUMO

Metastasis is the main cause of death from muscle-invasive urothelial carcinoma of the bladder (UCB), and the metastatic potential of tumors is often unpredictable. The role of Dachshund homolog 2 gene (DACH2) in tumorigenesis remains unexplored. We aimed to investigate whether DACH2 can be used as a biomarker to predict metastasis and prognosis of muscle-invasive UCB in a sequential training and validation fashion. For the training set (n = 40), compared with UCB patients without lymph node (LN) metastasis, both DACH2 protein and mRNA expression were greatly increased in case-matched patients with LN metastasis. For the independent validation set (n = 243), patients with primary UCB that did not express DACH2 had a longer metastasis-free survival (MFS) and overall survival (OS) than did those with tumors expressing DACH2 (5-year MFS: 88% [95% CI 80-96] versus 19% [95% CI 7-31], p < 0.001; 5-year OS: 93% [95% CI 87-99] versus 37% [95% CI 23-51], p < 0.001). Multivariable analysis of DACH2 status showed hazard ratios of 7.34 (95% CI 3.15-11.87, p < 0.001) for MFS and 3.96 (95% CI 2.04-7.16, p < 0.001) for OS which were much higher than hazard ratios associated with other independent risk factors. Collectively, DACH2 is an independent prognostic marker that can be used at initial diagnosis of UCB to identify patients who have a high potential to develop metastasis.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/secundário , Adulto , Idoso , Biomarcadores Tumorais/genética , Proteínas de Ligação a DNA , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Músculos/patologia , Invasividade Neoplásica/patologia , Proteínas Nucleares/genética , Prognóstico , Estudos Prospectivos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Fatores de Risco , Fatores de Transcrição/genética , Neoplasias da Bexiga Urinária/genética
11.
Zhonghua Yi Xue Za Zhi ; 94(17): 1330-3, 2014 May 06.
Artigo em Zh | MEDLINE | ID: mdl-25142855

RESUMO

OBJECTIVE: To observe the expression of cyclophilin A (CyPA) and the effects of lipopolysaccharide (LPS) on CyPA expression in synovial fibroblasts (SF) from patients with rheumatoid arthritis (RA) and evaluate the potential significance of CyPA in the regulation of the onset and development of inflammation process in RA patients. METHODS: SF were separated and cultured from synovial tissues of 12 patients with RA, 9 with osteoarthritis (OA) and 5 with knee trauma. The protein and mRNA expression levels of CyPA in SF were detected by Western blot (WB) and real-time quantitative polymerase chain reaction (RT-qPCR) respectively. Correlation analysis was conducted between the protein expression of CyPA in SFs and clinical parameters. Then the effects of LPS on CyPA in SF from 3 groups were detected. RESULTS: The expression levels of CyPA protein and mRNA in RA group were 0.86 ± 0.47 and 0.54 ± 0.22 respectively, significantly higher than those in OA group (0.40 ± 0.31 and 0.03 ± 0.02, P < 0.05) and trauma group (0.34 ± 0.21 and 0.03 ± 0.01, P < 0.05). The protein expression level of CyPA in SF of RA group had positive correlations with erythroeyte sedimentation rate (ESR), rheumatoid factor (RF) and swelling joint counts (SJC) (P < 0.05). After LPS treatment, CyPA protein and mRNA levels were 2.65 ± 1.16 and 1.82 ± 0.39 in RA SF and they were significantly higher than those in RA SF without LPS treatment (P < 0.05). The CyPA expression of SF from OA and trauma groups slightly decreased after LPS treatment.However the differences were not statistically significant (P > 0.05). CONCLUSION: The expression of CyPA is up-regulated in SF and it is positively correlated with ESR, RF and SJC in RA patients. It indicates that CyPA may be involved in the regulation of the onset and development of inflammation process of RA. And LPS may promote the expression of CyPA in SF of RA patients.


Assuntos
Artrite Reumatoide/metabolismo , Ciclofilina A/metabolismo , Fibroblastos/metabolismo , Idoso , Feminino , Humanos , Lipopolissacarídeos/toxicidade , Masculino , Pessoa de Meia-Idade , Membrana Sinovial/citologia , Membrana Sinovial/metabolismo
12.
Heliyon ; 10(3): e24818, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38327427

RESUMO

Rheumatoid arthritis (RA) is an autoimmune disease associated with an increased risk of disability. Due to its slow progression, timely diagnosis and treatment during the early stages can effectively decelerate disease advancement. Consequently, there is a pressing need to investigate additional biomarkers and therapeutic targets relevant to RA diagnosis. Mitochondrial autophagy, a biological process that regulates the quantity of mitochondria, is intricately linked to the development of tumor diseases. However, the role of autophagy in RA remains unclear. To address this, transcriptome data from the GEO database were collected for RA and its controls and subjected to differential expression analysis. The differentially expressed genes obtained were then intersected with mitochondrial autophagy-related genes. Subsequently, the overlapping genes were further intersected with genes from critical modules obtained through the weighted co-expression network algorithm. Diagnostic genes were identified, and diagnostic models were constructed for the resulting genes using the random forest and LASSO algorithms. The model achieved an AUC of 0.916 in the GSE93272 dataset and 0.951 in the GSE17755 dataset. Additionally, qPCR experiments were conducted on the diagnostic genes. Finally, we explored the correlation between the abundance of immune cell infiltration and diagnostic genes, constructing a drug-gene interaction network. The diagnostic genes identified in this study can serve as a reference for early diagnosis and the discovery of therapeutic targets in RA.

13.
Aging (Albany NY) ; 16(2): 1249-1275, 2024 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-38271056

RESUMO

Disulfidptosis is a recently identified type of programmed cell death. It is characterized by aberrant accumulation of intracellular disulfides. The clinical implications of disulfidptosis in clear cell renal cell carcinoma (ccRCC) remain unclear. A series of bioinformatics approaches were employed to analyze ten disulfidptosis-related molecules. Firstly, the expression patterns of the disulfidptosis-related molecules were different between normal and ccRCC tissues. A comprehensive cohort of patients with ccRCC was then assembled from three public databases and subjected to cluster analysis based on disulfidptosis-related molecules. Consensus cluster analysis revealed three distinct disulfidptosis clusters. We then conducted weighted gene co-expression network analysis (WGCNA) to identify highly correlated genes. 267 hub genes were screened out through WGCNA, and three gene clusters were then determined. Finally, we identified 87 genes with prognostic value and then used them to develop a disulfidptosis scoring (DSscore) system, which was proven to independently predict survival in ccRCC. Patients in the high-DSscore group exhibited a significant survival advantage and better immunotherapeutic responses compared with those in the low-DSscore group. However, the patients in the low-DSscore group exhibited a greater degree of chemotherapeutic response. In addition, the expression of disulfidptosis-related molecules was validated by qRT-PCR, and the potential of disulfidptosis-related molecules to indicate distinct cell subtypes were validated by single-cell RNA-sequencing. In conclusion, DSscore is a promising index for predicting the prognosis and efficacy of immunotherapy in patients with ccRCC and may provide a basis for novel strategies for future studies.


Assuntos
Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Prognóstico , Apoptose , Neoplasias Renais/genética , Neoplasias Renais/terapia , Microambiente Tumoral
14.
Adv Rheumatol ; 64(1): 18, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438904

RESUMO

INTRODUCTION: If a large amount of urate crystals is deposited in a joint cavity for an extended period of time, bone erosion will occur and gradually cause skeletal muscle necrosis and joint deformity. The aim of this study was to describe the clinical characteristics and factors associated with bone erosion in gout patients with tophi. METHODS: A total of 210 gout patients with tophi were enrolled and divided into a bone erosion group (n = 135) and a non-bone erosion group (n = 75). Digital radiography (DR) was performed to detect bone erosion in the elbow, wrist, knee, ankle joints, interphalangeal and metatarsophalangeal joints. The clinical characteristics were recorded and compared between the two groups. Multivariate logistic regression analysis was conducted to explore the factors associated with bone erosion. RESULTS: Compared with the non-bone erosion group, the bone erosion group had an older age, longer disease duration of gout and tophi, higher level of serum creatinine (sCr), higher proportion of drinking history and ulceration, and a lower glomerular filtration rate (GFR). Univariate logistic regression analysis results showed that sex, age, body mass index (BMI), gout duration, tophi duration, GFR, white blood cell (WBC) count, sCr level, smoking history, drinking history, and presence of ulceration were associated with bone destruction. Multivariable logistic regression analysis results indicated that tophi duration, drinking history, ulceration and sCr were positively and independently related to bone erosion. CONCLUSIONS: Tophi patients with bone erosion presented different clinical characteristics. Tophi duration, drinking history, ulceration and sCr were associated with bone erosion in gout patients with tophi.


Assuntos
Gota , Humanos , Gota/complicações , Fatores de Risco , Fumar/efeitos adversos , Índice de Massa Corporal , Taxa de Filtração Glomerular
15.
Zhonghua Yi Xue Za Zhi ; 93(37): 2989-92, 2013 Oct 08.
Artigo em Zh | MEDLINE | ID: mdl-24401592

RESUMO

OBJECTIVE: To evaluate the efficacy of recombinant human tumor necrosis factor-α receptor II: IgG fusion protein (RhTNFR:Fc) local injection in collagen-induced arthritis (CIA) of rats. METHODS: Twenty-four CIA rats were randomly divided into 3 groups: single therapy (Group I), multiply therapies (Group II) and control (Group III). Group I received normal saline thrice after a single RhTNFR:Fc local treatment while Groups II and III had 4 times of RhTNFR:Fc or normal saline local injection. The severities of right ankle and systemic inflammation were assessed by arthritis index (AI) at baseline and every week after local injection (visits 1, 2, 3 and 4). Serum C reactive protein (CRP) was measured after the last visit. And right ankles were further examined through radiology and pathology. RESULTS: Local or systemic AI of Group I were significantly lower than that of baseline at visit 1 (P < 0.05), but increased during other visits. And local or systemic AI of Group II gradually decreased at each follow-up, but AI of Group III showed no decline. The radiographic scores (5.70±0.67 and 4.90±0.73), histopathological scores (6.00±0.67 and 3.80±0.91) and serum CRP concentration (7.50±0.87 and 3.09±0.76 µg/ml) of Group I and Group II were lower than those of Group III (6.60±1.26, 7.10±0.7 and 12.15±3.47 µg/ml, P < 0.05). And all these parameters of Group I were higher than those of Group II (P < 0.05). CONCLUSION: Local injection of RhTNFR:Fc can effectively alleviate disease activity of CIA and reduce CRP concentration, radiographic and histopathological scores. Multiple therapies show a better efficacy than single injection.


Assuntos
Artrite Experimental/terapia , Proteínas Recombinantes de Fusão/uso terapêutico , Fator de Necrose Tumoral alfa/uso terapêutico , Animais , Feminino , Ratos , Ratos Sprague-Dawley
16.
Comb Chem High Throughput Screen ; 26(11): 1974-1989, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36475339

RESUMO

BACKGROUND: Bridging integrator 3 (BIN3) has been reported to play a key role in certain tumors. Nevertheless, little is known about the role and clinical value of BIN3 in esophagus carcinoma (ESCA). This study aimed to investigate the pathological and prognostic role of BIN3 in ESCA patients. METHODS: Genes significantly correlated with the prognosis of ESCA patients were screened and identified by comprehensive analysis of differentially expressed genes associated with overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) in ESCA. The expression of BIN3, pathological features correlation and subgroup overall survival analysis were performed using The Cancer Genome Atlas (TCGA) and GTEx databases. Moreover, the potential signaling pathways in which BIN3 was involved were analyzed by GO-KEGG enrichment analysis and gene set enrichment analysis (GSEA). Immune infiltrates correlation of BIN3 in ESCA was performed by TIMER and ssGSEA. The influence of BIN3 on epithelial-mesenchymal transition (EMT) was validated by western blot. RESULTS: There were two differentially expressed genes related to the prognosis of ESCA patients, which were identified from three gene clusters associated with overall survival (OS), diseasespecific survival (DSS) and progression-free interval (PFI) in ESCA patients. The BIN3 mRNA level was found to be significantly decreased in ESCA compared to normal tissues (p < 0.05). The decreased expression of BIN3 in ESCA was significantly correlated with the clinical stage (p = 0.015), T stage (p < 0.05), histological type (p < 0.001), age (p < 0.05) and gender (p < 0.05). ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (<=60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. GO-KEGG enrichment analysis revealed that BIN3 was involved in endocytosis. GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). In addition, BIN3 overexpression inhibited N-cadherin expression and promoted E-cadherin expression in ESCA cell lines TE-1. CONCLUSION: These results suggest that BIN3 might be a potential prognostic biomarker in ESCA. BIN3 functions as a tumor-suppressor role in ESCA, which is significantly associated with the immune infiltration of ESCA.


Assuntos
Carcinoma , Neoplasias Esofágicas , Humanos , Masculino , Regulação para Baixo , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Diferenciação Celular , Proteínas dos Microfilamentos
17.
Front Endocrinol (Lausanne) ; 14: 1167756, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37143721

RESUMO

Objective: This study aimed to analyze the effect of urate deposition (UD) on bone erosion and examine the association between the volume of monosodium urate (MSU) crystals and an improved bone erosion score method, as measured in the metatarsophalangeal (MTP) joints of patients with gout. Materials and methods: Fifty-six patients diagnosed with gout using the 2015 European League Against Rheumatism and American College of Rheumatology criteria were enrolled. MSU crystals volume at each MTP joint was measured using dual-energy computed tomography (DECT) images. The degree of bone erosion was evaluated with the modified Sharp/van der Heijde (SvdH) erosion scoring system based on CT images. Differences in clinical features between patients with (UD group) and without (non-UD group) UD were assessed, and the correlation between erosion scores and urate crystal volume was analyzed. Results: The UD and non-UD groups comprised 30 and 26 patients, respectively. Among the 560 MTP joints assessed, 80 showed MSU crystal deposition, and 108 showed bone erosion. Bone erosion occurred in both groups but was significantly less severe in the non-UD group (p <0.001). Both groups had equivalent levels of serum uric acid (p=0.200). Symptom duration was significantly longer in the UD group (p=0.009). The UD group also had a higher rate of kidney stones (p=0.023). The volume of MSU crystals was strongly and positively associated with the degree of bone erosion (r=0.714, p <0.001). Conclusion: This study found that patients with UD show significant increased bone erosion than those without UD. The volume of MSU crystals is associated with the improved SvdH erosion score based on CT images, regardless of serum uric acid level, demonstrating the potential of combining DECT and serum uric acid measurements in helping optimize the management of patients with gout.


Assuntos
Gota , Ácido Úrico , Humanos , Tomografia Computadorizada por Raios X/métodos , Gota/complicações , Gota/diagnóstico por imagem
18.
Cell Rep Med ; 4(10): 101240, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37852185

RESUMO

To construct a urine extracellular vesicle long non-coding RNA (lncRNA) classifier that can detect high-grade prostate cancer (PCa) of grade group 2 or greater and estimate the risk of progression during active surveillance, we identify high-grade PCa-specific lncRNAs by combined analyses of cohorts from TAHSY, TCGA, and the GEO database. We develop and validate a 3-lncRNA diagnostic model (Clnc, being made of AC015987.1, CTD-2589M5.4, RP11-363E6.3) that can detect high-grade PCa. Clnc shows higher accuracy than prostate cancer antigen 3 (PCA3), multiparametric magnetic resonance imaging (mpMRI), and two risk calculators (Prostate Cancer Prevention Trial [PCPT]-RC 2.0 and European Randomized Study of Screening for Prostate Cancer [ERSPC]-RC) in the training cohort (n = 350), two independent cohorts (n = 232; n = 251), and TCGA cohort (n = 499). In the prospective active surveillance cohort (n = 182), Clnc at diagnosis remains a powerful independent predictor for overall active surveillance progression. Thus, Clnc is a potential biomarker for high-grade PCa and can also serve as a biomarker for improved selection of candidates for active surveillance.


Assuntos
Neoplasias da Próstata , RNA Longo não Codificante , Masculino , Humanos , RNA Longo não Codificante/genética , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Gradação de Tumores , Biomarcadores
19.
Int Immunopharmacol ; 122: 110560, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37423153

RESUMO

OBJECTIVES: Our study profiled the CD4 + T-cell-derived exosomes from patients with rheumatoid arthritis (RA) using proteomics. METHODS: Proteomic analysis of CD4 + T-cell-derived exosomes was performed by tandem mass tags (TMT) combined with LC-MS/MS. We validated the most significantly upregulated and downregulated proteins using ELISA and WB. RESULTS: The proteomic results showed that there were 3 upregulated differentially expressed proteins and 31 downregulated differentially expressed proteins in the RA group. The results indicated that dihydropyrimidinase-related protein 3 (DPYSL3) was significantly upregulated in CD4 + T-cell-derived exosomes, whereas proteasome activator complex subunit 1 (PSME1) was significantly downregulated in the RA group. Bioinformatics analysis showed that proteins were enriched in "positive regulation of gene expression", "antigen processing and presentation", "acute-phase response" and "PI3K-AKT signaling" pathways. ELISA verified that compared to the control group, the RA group showed significant upregulation of DPYSL3, and downregulation of PSME1 in CD4 + T-cell-derived exosomes. CONCLUSIONS: The proteomic analysis results of CD4 + T-cell-derived exosomes from patients with RA suggest that these differentially expressed proteins may be involved in RA pathogenesis. DPYSL3 and PSME1 may become useful biomarkers for RA.


Assuntos
Artrite Reumatoide , Exossomos , Humanos , Exossomos/metabolismo , Proteômica , Cromatografia Líquida , Fosfatidilinositol 3-Quinases/metabolismo , Espectrometria de Massas em Tandem , Linfócitos T CD4-Positivos
20.
Rheumatol Int ; 32(7): 2011-6, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21479602

RESUMO

To investigate the prevalence of hepatitis B surface antigen (HBsAg), a seromarker for current infection of hepatitis B virus, in patients with ankylosing spondylitis (AS) from south China and to evaluate its association with human leukocyte antigen (HLA)-B27. The prevalence of HBsAg was retrospectively investigated in 439 patients with AS, 606 age- and sex-matched general individuals, 172 patients with other spondyloarthropathy (SpA), 698 patients with rheumatoid arthritis (RA), and 220 patients with osteoarthritis (OA). The positive rate of HBsAg in AS group was compared with those of the general population group and other disease groups, respectively, and the prevalence of HBsAg was compared between HLA-B27-positive and HLA-B27-negative patients with AS. The positive rate of HBsAg in AS patients, general population, other-SpA, RA, and OA patients were 25.39, 12.87, 14.53, 9.60, and 8.18%, respectively. The HBsAg prevalence of AS group was statistically higher than those of any other groups (P < 0.05). The prevalence of HBsAg in HLA-B27-positive and HLA-B27-negative AS patients were 26.68 and 14.49%, respectively, the positive rate of HBsAg in HLA-B27-positive AS patients was statistically higher than that of HLA-B27-negative AS patients (P < 0.05). The prevalence of HBsAg in AS patients was higher than those in general population, patients with other-SpA, RA, and OA. The high HBsAg prevalence in AS patients might be associated with their high frequency of HLA-B27 gene.


Assuntos
Antígeno HLA-B27/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Espondilite Anquilosante/epidemiologia , Espondilite Anquilosante/imunologia , Adolescente , Adulto , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/imunologia , China/epidemiologia , Feminino , Antígenos de Superfície da Hepatite B/análise , Humanos , Masculino , Osteoartrite/epidemiologia , Osteoartrite/imunologia , Prevalência , Estudos Retrospectivos , Adulto Jovem
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