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1.
Cancer Immunol Immunother ; 72(9): 2991-3002, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37289256

RESUMO

BACKGROUND: This study aimed to assess the efficacy and safety of geptanolimab (GB226), a fully humanized, recombinant anti-programmed cell death-1 monoclonal antibody, in Chinese patients with refractory or relapsed (r/r) primary mediastinal large B-cell lymphoma (PMBCL). METHODS: This was a multicenter, open-label, single-arm phase II study (Gxplore-003), conducted at 43 hospitals in China (NCT03639181). Patients received geptanolimab intravenously at a dose of 3 mg/kg every 2 weeks until documented confirmed disease progression, intolerable toxicity, or any other cessation criteria was met. The primary endpoint was objective response rate (ORR) in the full analysis set assessed by the independent review committee (IRC) according to the Lugano Classification 2014. RESULTS: This study was prematurely terminated due to the slow rate of patient accrual. Between Oct 15th, 2018 and Oct 7th, 2020, 25 patients were enrolled and treated. By the data cutoff date on Dec 23rd, 2020, the IRC-assessed ORR was 68.0% (17/25; 95% confidence interval [CI] 46.5-85.1%), with the complete response rate of 24%. The disease control rate was 88% (22/25; 95%CI 68.8-97.5%). Median duration of response was not reached (NR) (95%CI, 5.62 months to NR), with 79.5% of patients having response durations of more than 12 months. Median progression-free survival was NR (95%CI, 6.83 months to NR). Treatment-related adverse events (TRAEs) were reported in 20 of 25 (80.0%) patients, and grade 3 or higher TRAEs occurred in 11 of 25 (44%) patients. No treatment-related deaths occurred. The immune-related adverse events (irAEs) of any grade were observed in 6 (24.0%) patients, and no grade 4 or grade 5 irAEs were reported. CONCLUSION: Geptanolimab (GB226) demonstrated promising efficacy and a manageable safety profile in Chinese patients with r/r PMBCL.


Assuntos
Linfoma Difuso de Grandes Células B , Neoplasias do Timo , Adulto , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Anticorpos Monoclonais/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico
2.
J Biochem Mol Toxicol ; 37(8): e23211, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36120848

RESUMO

The above article, published online on 19 September 2022 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/abs/10.1002/jbt.23211), has been retracted by agreement between the authors, the journal Editor in Chief, Hari Bhat, and Wiley Periodicals, LLC. The article is being retracted at the authors' request because some of the data underlying this article refer to a different cell line from the one reported in it. As a result, the article's conclusions do not accurately reflect the full data and cannot be considered reliable.

3.
Opt Express ; 30(23): 41171-41180, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36366601

RESUMO

A high-average-power, high-pulse-energy picosecond chirped pulse amplification (CPA) laser system based on an extra-large-mode-area (XLMA) triple-clad fiber (TCF) was demonstrated. The ultrashort pulses, generated from all-fiber mode-locked oscillator, stretched and then were pre-amplified to 10 W through a series of fiber power amplifiers. Subsequently, the average output power was amplified to 620 W corresponding to a pulse energy of 0.62 mJ via XLMA TCF. Additionally, the amplified pulses were compressed to a pulse duration of 7.6 ps with an average power of 423 W and a compression efficiency of 68.2%. The ultrashort laser is a promising light source for application of water-guided laser processing, albeit with a beam quality factor of 20 and 21 along two orthogonal axes.

4.
BMC Cancer ; 21(1): 996, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488675

RESUMO

BACKGROUND: Esophageal cancer is a common malignant tumor and its 5-year survival rate is much lower than 30% due to its invasiveness and pronounced metastasis ability, as well as the difficulty in early diagnosis. This study aimed to elucidate the molecular mechanism of ubiquitin conjugating enzyme E2 C (UBE2C) in esophageal squamous cell carcinoma (ESCC). METHODS: In this study, we conducted a comprehensive evaluation of the UBE2C expression in ESCC by collecting the protein and mRNA expression data (including in-house RNA-seq, in-hosue immunohistochemistry, TCGA-GTEx RNA-seq and tissue microarray) to calculate a combined standardized mean difference (SMD) and summary receiver operating characteristic curve (sROC). Kaplan-Meier (K-M) method was used for survival analysis. We also explored the mechanism of UBE2C in ESCC by combing the differentially expressed genes (DEGs) of ESCC, related-genes of UBE2C in ESCC and the putative miRNAs and lncRNAs which may regulate UBE2C. RESULTS: UBE2C protein and mRNA were highly expressed in ESCC tissues (including 772 ESCC tissue samples and 1837 non-cancerous tissue control samples). The pooled SMD of UBE2C expression values was 1.98 (95% CI: 1.51-2.45, p < 0.001), and the the area under the curve (AUC) of the sROC was 0.93 (95% CI: 0.90-0.95). The results of survival analysis suggested that UBE2C is likely to play different roles in different stages of the ESCC. Pathway anaylsis showed that UBE2C mainly influenced the biological function of esophageal cancer by synergistic effects with CDK1, PTTG1 and SKP2. We also constructed a potential UBE2C-related ceRNA network for ESCC (HCP5/has-miR-139-5p/UBE2C). CONCLUSION: UBE2C mRNA and protein level were highly expressed in ESCC and UBE2C was likely to play different roles in different stages of the ESCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , RNA-Seq/métodos , Enzimas de Conjugação de Ubiquitina/metabolismo , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Biologia Computacional , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Prognóstico , RNA Longo não Codificante/genética , Taxa de Sobrevida , Enzimas de Conjugação de Ubiquitina/genética
5.
Am J Hematol ; 96(11): 1481-1490, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34449095

RESUMO

Extranodal natural killer/T-cell lymphoma, nasal-type (ENKTL) is a distinct subtype of non-Hodgkin lymphoma and most of the patients presented localized disease. Combined modality therapy (CMT), namely chemotherapy combined with radiotherapy, has been recommended for patients with early-stage ENKTL. However, the optimal CMT has not been fully clarified. This study reports the efficacy and toxicity of sequential P-GEMOX (pegaspargase, gemcitabine and oxaliplatin) and radiotherapy in a large Chinese cohort comprising of 202 patients diagnosed with early-stage ENKTL from six medical centers. The observed best overall response rate was 96.0% and 168 (83.2%) patients achieved complete remission. With a median follow-up of 44.1 months, the 3-year progression-free survival (PFS) and overall survival (OS) were 74.6% and 85.2%, respectively. Multivariate analysis suggested that extensive primary tumor (PFS, hazard ratio [HR] 3.660, 95% CI 1.820-7.359, p < 0.001; OS, HR 3.825, 95% CI 1.442-10.148, p = 0.007) and Eastern Cooperative Oncology Group performance status ≥ 2 (PFS, 3.042, 95% CI 1.468-6.306, p = 0.003; OS, HR 3.983, 95% CI 1.678-9.457, p = 0.02) were independent prognostic factors for survival outcomes. Among the established prognostic models for ENKTL, the nomogram-revised risk index model had optimal prognostic risk stratification ability (PFS, p < 0.001; OS, p < 0.001) and relatively balanced population distribution. The adverse events of this CMT were well-tolerated and manageable. In conclusion, sequential P-GEMOX and radiotherapy showed favorable efficacy with acceptable toxicity, and could be an effective treatment option for early-stage ENKTL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Asparaginase/uso terapêutico , Desoxicitidina/análogos & derivados , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Linfoma Extranodal de Células T-NK/radioterapia , Polietilenoglicóis/uso terapêutico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Asparaginase/efeitos adversos , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Feminino , Humanos , Linfoma Extranodal de Células T-NK/diagnóstico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Polietilenoglicóis/efeitos adversos , Prognóstico , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
6.
BMC Musculoskelet Disord ; 22(1): 27, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407312

RESUMO

BACKGROUND: To investigate the imaging features of hemangiomas in long tabular bones for better diagnosis. METHODS: Twenty-four patients with long bone hemangiomas confirmed by pathology were enrolled. Nineteen patients had plain radiography, fourteen patients had computed tomography (CT) and eleven had magnetic resonance imaging (MRI). The hemangioma was divided into medullary [13], periosteal [6] and intracortical type [5]. RESULTS: Among 19 patients with plain radiography, eleven patients were medullary, three periosteal, and five intracortical. In the medullary type, the lesion was primarily osteolytic, including five cases with irregular and unclear rims and one lesion having osteosclerotic and unclear rims. In three patients with the periosteal type, the lesion had clear rims with involvement of the cortical bone in the form of bone defect, including two cases with local thickened bone periosteum and one case having expansile periosteum. Five intracortical hemangiomas had intracortical osteolytic lesions with clear margins. Among 14 patients with CT imaging, 8 cases were medullary, three periosteal, and three intracortical. Among 8 medullary hemangiomas, one had ground glass opacity, and seven had osteolytic, expansile lesions like soft tissue density with no calcification. In three periosteal cases, the lesion was osteolytic with thickened periosteum and narrowed medullary cavity. In three intracortical hemangiomas, the lesion was of even soft tissue density with no calcification. Among 11 patients with MRI imaging, seven were medullary, two periosteal, and two intracortical. Among 7 medullary lesions, six were of hypointense signal on T1WI and hyperintensesignal on T2 WI. In two periosteal cases, the periosteum was thickened, with one case being of equal signal, and the other having no signal. Two intracortical hemangiomas were both of slightly low signal on T1WI but hyperintense signal on T2WI. CONCLUSIONS: The long bone hemangiomas had characteristic cystic honeycomb-like presentations in plain radiograph. CT and MRI imagings are helpful for diagnosis of hemangiomas in long bone.


Assuntos
Neoplasias Ósseas , Hemangioma , Neoplasias Ósseas/diagnóstico por imagem , Hemangioma/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Radiografia , Tomografia Computadorizada por Raios X
7.
Opt Express ; 28(22): 32764-32776, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33114954

RESUMO

We investigate an all-fiber all-polarization-maintaining dispersion-managed ultrafast fiber laser mode-locked by nonlinear polarization evolution in polarization-maintaining fibers both numerically and experimentally. We find that the laser can operate in different regions among a wide net dispersion, including dispersion-managed solitons, dispersion-managed dissipative solitons, bound state solitons and noise-like pulses. The laser generates the dispersion-managed soliton pulses with a maximum 3 dB bandwidth of 37.84 nm, which can be further compressed to 161.37 fs. Moreover, pulses generation simulation under different net dispersion condition has been carried out. Nonlinear pulse evolution dynamics in laser cavity has been analyzed through numerical simulation as well. The results are basically consistent with the experimental ones.

8.
Opt Express ; 27(23): 34103-34112, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31878466

RESUMO

Parabolic pulses with linear self-phase-modulation-induced frequency chirp are attractive in ultrafast laser fiber amplification system for the functionality of nonlinearities suppression. In this paper, we present an effective way of parabolic pulse evolution by passive spectral amplitude shaping with a pair of chirped fiber Bragg gratings (CFBG). By this approach, a high-energy high-peak-power Yb-doped fiber chirped pulse amplification (CPA) system is demonstrated. The oscillator is a dispersion-managed passively mode-locked Yb-doped fiber laser with a broadband Gaussian-shaped spectrum which is evolved to parabola in a following preamplifier with pre-chirping management by a CFBG compressor. The pulses are then stretched with a CFBG stretcher, based on frequency-to-time mapping, the temporal profiles of the pulses show an identical parabolic envelope to the spectrum. The shaped pulses are further amplified with three stages of all-fiber amplifiers and compressed by a grating-pair compressor. The pulse duration is compressed to 172 fs with a pulse energy of 27 µJ. The central pulse encompasses 72% of total pulse energy, corresponding to a pulse peak power of 113 MW. No obvious pulse degeneration is noticed at nonlinearity accumulation B-integral as high as 12 rad. This configuration shows a significant potential for nonlinearity tolerance in high-energy operation compared with conventional CPA system.

9.
Exp Mol Pathol ; 107: 141-157, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30768923

RESUMO

OBJECTIVE: To explore the clinical significance and potential molecular mechanism of endothelin receptor type B (EDNRB) in hepatocellular carcinoma (HCC). METHODS: Immunohistochemistry was used to detect EDNRB protein expression level in 67 HCC paraffin embedded tissues and adjacent tissues. Correlations between EDNRB expression level and clinicopathologic parameters were analyzed in our study. The expression level and clinical significance of EDNRB in HCC were also evaluated from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The cBioPortal for Cancer Genomics was employed to analyze the EDNRB related genes, and Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Protein-Protein Interaction (PPI) network were conducted for those EDNRB related genes. RESULTS: Lower expression level of EDNRB in HCC was verified by immunohistochemistry than adjacent tissues (P < 0.0001). The expression level of EDNRB in HCC tissues was lower than normal control liver tissues based on TCGA and GEO data (standard mean difference [SMD] = -1.48, 95% [confidence interval] CI: -1.63-(-1.33), Pheterogeneity = 0.116, I2 = 32.4%). Kaplan-Meier analysis showed that HCC patients with lower EDNRB expression were more prone to poor prognosis (P = .0041). The top terms of GO annotation in biological process, cellular component and molecular function were vasculature development, actin filament and transmembrane receptor protein kinase activity, respectively. The KEGG pathway enrichment analysis confirmed that EDNRB related genes mainly participated in Vascular smooth muscle contraction, cGMP-PKG signaling pathway and Focal adhesion pathways. The result of PPI network construction showed that KDR, VEGFC, FLT1, CDH5 and ADCY4 were possible to become the core genes of EDNRB related genes, which need further experiments to confirm. CONCLUSION: Our study provides novel findings and insights on the molecular pathogenesis of HCC from EDNRB view.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Receptor de Endotelina B/biossíntese , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptor de Endotelina B/análise
10.
Opt Express ; 26(5): 5609-5615, 2018 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-29529763

RESUMO

We demonstrate a 2.8 µm gas Raman laser in a methane-filled hollow-core negative-curvature fiber with average power of 113 mW, pulse energy of 113 µJ and estimated peak power of 9.5 MW. Raman quantum efficiency of 40% has been reached from the pump source at 1.064 µm to the 2nd order vibrational Stokes at 2.812 µm using 1.8 MPa methane gas. To our knowledge, this is the first high peak power fiber-based gas Raman laser in mid-infrared region and a range of applications in supercontinuum generation, laser surgery, molecular tracing and gas detection are in prospect.

11.
BMC Cancer ; 17(1): 655, 2017 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-28927388

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) has led to the highest cancer-related mortality for decades. To enhance the efficiency of early diagnosis and therapy, more efforts are urgently needed to reveal the origins of NSCLC. In this study, we explored the effect of miR-542-5p in NSCLC with clinical samples and in vivo models and further explored the prospective function of miR-542-5p though bioinformatics methods. METHODS: A total of 125 NSCLC tissue samples were collected, and the expression of miR-542-5p was detected by qRT-PCR. The relationship between miR-542-5p level and clinicopathological features was analyzed. The effect of miR-542-5p on survival time was also explored with K-M survival curves and Cox's regression. The effect of miR-542-5p on the tumorigenesis of NSCLC was verified with a chick chorioallantoic membrane (CAM) model. The potential target genes were predicted by bioinformatics tools, and relevant pathways were analyzed by GO and KEGG. Several hub genes were validated by Proteinatlas. RESULTS: The expression of miR-542-5p was down-regulated in NSCLC tissues, and consistent results were also found in the subgroups of adenocarcinoma and squamous cell carcinoma. Down-regulation of miR-542-5p was found to be connected with advanced TNM stage, vascular invasion, lymphatic metastasis and EGFR. Survival analyses showed that patients with lower miR-542-5p levels had markedly poorer prognosis. Both tumor growth and angiogenesis were significantly suppressed by miR-542-5p mimic in the CAM model. The potential 457 target genes of miR-542-5p were enriched in several key cancer-related pathways, such as morphine addiction and the cAMP signaling pathway from KEGG. Interestingly, six genes (GABBR1, PDE4B, PDE4C, ADCY6, ADCY1 and GIPR) from the cAMP signaling pathway were confirmed to be overexpressed in NSCLCs tissues. CONCLUSIONS: This evidence suggests that miR-542-5p is a potential tumor-suppressed miRNA in NSCLC, which has the potential to act as a diagnostic and therapeutic target of NSCLC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , MicroRNAs/fisiologia , Neovascularização Patológica/metabolismo , Células A549 , Animais , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Embrião de Galinha , Membrana Corioalantoide/patologia , Feminino , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Genes Supressores de Tumor , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Transplante de Neoplasias , Prognóstico , Interferência de RNA
12.
BMC Musculoskelet Disord ; 18(1): 103, 2017 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-28288612

RESUMO

BACKGROUND: The cementoma is a common disease of the dental root apex, which generally occurs in the maxilla and the mandible, but the cementoma occurring in the long bone is rare. Moreover, the incidence of cementoma in the calcaneus is extremely infrequent. CASE PRESENTATION: The present study reports an unusual case of a 19-year-old girl, who complained of pain in the left heel. Subsequent radiographs and computed tomography (CT) were used in the diagnosis. The imaging features of the lesion included a radiopaque matrix and radiolucent tissue, particularly an arc-shaped fat band. An excisional biopsy was performed. Histopathological examination confirmed the diagnosis of cementoma in the calcaneus. After the operation, the patient was followed up without recurrence. CONCLUSIONS: Imaging examination plays an important role in the differential diagnosis of cementoma of the calcaneus.


Assuntos
Calcâneo/diagnóstico por imagem , Calcâneo/cirurgia , Cementoma/diagnóstico por imagem , Cementoma/cirurgia , Transplante Ósseo/métodos , Feminino , Seguimentos , Humanos , Adulto Jovem
13.
BMC Musculoskelet Disord ; 15: 342, 2014 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-25306531

RESUMO

BACKGROUND: Plexiform schwannoma (PS) is a rare, peripheral nerve sheath tumor arranged in a plexiform pattern. CASE PRESENTATION: We report an unusual case of a 19-year-old woman, who complained of pain in the plantar aspect of the left foot. Magnetic resonance image (MRI) demonstrates three solitary nodules of varying sizes in the deep soft tissue of the plantar aspect of the foot that are homogeneously isointense to skeletal muscle on T1-weighted images and hyperintense on T2-weighted fat-suppressed images, especially the rim of the lesion. Subsequent pathological examination confirmed the diagnosis of PS. CONCLUSION: MRI characteristic plays an important role in detecting this rare lesion. A review of the literature on PS is also presented.


Assuntos
Pé/patologia , Neurilemoma/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Feminino , Pé/cirurgia , Humanos , Neurilemoma/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Adulto Jovem
14.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(1): 119-124, 2024 Jan 15.
Artigo em Zh | MEDLINE | ID: mdl-38225851

RESUMO

Objective: To summarize the research progress on the role of macrophage-mediated osteoimmune in osteonecrosis of the femoral head (ONFH) and its mechanisms. Methods: Recent studies on the role and mechanism of macrophage-mediated osteoimmune in ONFH at home and abroad were extensively reviewed. The classification and function of macrophages were summarized, the osteoimmune regulation of macrophages on chronic inflammation in ONFH was summarized, and the pathophysiological mechanism of osteonecrosis was expounded from the perspective of osteoimmune, which provided new ideas for the treatment of ONFH. Results: Macrophages are important immune cells involved in inflammatory response, which can differentiate into classically activated type (M1) and alternatively activated type (M2), and play specific functions to participate in and regulate the physiological and pathological processes of the body. Studies have shown that bone immune imbalance mediated by macrophages can cause local chronic inflammation and lead to the occurrence and development of ONFH. Therefore, regulating macrophage polarization is a potential ONFH treatment strategy. In chronic inflammatory microenvironment, inhibiting macrophage polarization to M1 can promote local inflammatory dissipation and effectively delay the progression of ONFH; regulating macrophage polarization to M2 can build a local osteoimmune microenvironment conducive to bone repair, which is helpful to necrotic tissue regeneration and repair to a certain extent. Conclusion: At present, it has been confirmed that macrophage-mediated chronic inflammatory immune microenvironment is an important mechanism for the occurrence and development of ONFH. It is necessary to study the subtypes of immune cells in ONFH, the interaction between immune cells and macrophages, and the interaction between various immune cells and macrophages, which is beneficial to the development of potential therapeutic methods for ONFH.


Assuntos
Necrose da Cabeça do Fêmur , Osteonecrose , Humanos , Cabeça do Fêmur/patologia , Osteonecrose/terapia , Macrófagos/patologia , Inflamação , Necrose da Cabeça do Fêmur/patologia
15.
Diagnostics (Basel) ; 14(7)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38611581

RESUMO

PURPOSE: To develop and validate a deep-learning-based algorithm (DLA) that is designed to segment and classify metallic objects in topograms of abdominal and spinal CT. METHODS: DLA training for implant segmentation and classification was based on a U-net-like architecture with 263 annotated hip implant topograms and 2127 annotated spine implant topograms. The trained DLA was validated with internal and external datasets. Two radiologists independently reviewed the external dataset consisting of 2178 abdomen anteroposterior (AP) topograms and 515 spine AP and lateral topograms, all collected in a consecutive manner. Sensitivity and specificity were calculated per pixel row and per patient. Pairwise intersection over union (IoU) was also calculated between the DLA and the two radiologists. RESULTS: The performance parameters of the DLA were consistently >95% in internal validation per pixel row and per patient. DLA can save 27.4% of reconstruction time on average in patients with metallic implants compared to the existing iMAR. The sensitivity and specificity of the DLA during external validation were greater than 90% for the detection of spine implants on three different topograms and for the detection of hip implants on abdominal AP and spinal AP topograms. The IoU was greater than 0.9 between the DLA and the radiologists. However, the DLA training could not be performed for hip implants on spine lateral topograms. CONCLUSIONS: A prototype DLA to detect metallic implants of the spine and hip on abdominal and spinal CT topograms improves the scan workflow with good performance for both spine and hip implants.

16.
Sci Rep ; 14(1): 6268, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491150

RESUMO

3D SHINKEI neurography is a new sequence for imaging the peripheral nerves. The study aims at assessing traumatic brachial plexus injury using this sequence. Fifty-eight patients with suspected trauma induced brachial plexus injury underwent MR neurography (MRN) imaging in 3D SHINKEI sequence at 3 T. Surgery and intraoperative somatosensory evoked potentials or clinical follow-up results were used as the reference standard. MRN, surgery and electromyography (EMG) findings were recorded at four levels of the brachial plexus-roots, trunks, cords and branches. Fifty-eight patients had pre- or postganglionic injury. The C5-C6 nerve postganglionic segment was the most common (average 42%) among the postganglionic injuries detected by 3D SHINKEI MRN. The diagnostic accuracy (83.75%) and the specificity (90.30%) of MRN higher than that of EMG (p < 0.001). There was no significant difference in the diagnostic sensitivity of MRN compared with EMG (p > 0.05). Eighteen patients with brachial plexus injury underwent surgical exploration after MRN examination and the correlation between MRN and surgery was 66.7%. Due to the high diagnostic accuracy and specificity, 3D SHINKEI MRN can comprehensively display the traumatic brachial plexus injury. This sequence has great potential in the accurate diagnosis of traumatic brachial plexus injury.


Assuntos
Neuropatias do Plexo Braquial , Plexo Braquial , Humanos , Neuropatias do Plexo Braquial/diagnóstico por imagem , Neuropatias do Plexo Braquial/cirurgia , Imageamento por Ressonância Magnética/métodos , Plexo Braquial/lesões , Nervos Periféricos , Estudos Prospectivos
17.
Leukemia ; 38(4): 829-839, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38378844

RESUMO

Natural killer/T-cell lymphoma (NKTCL) is a highly heterogeneous disease with a poor prognosis. However, the genomic characteristics and proper treatment strategies for non-upper aerodigestive tract NKTCL (NUAT-NKTCL), a rare subtype of NKTCL, remain largely unexplored. In this study, 1589 patients newly diagnosed with NKTCL at 14 hospitals were assessed, 196 (12.3%) of whom had NUAT-NKTCL with adverse clinical characteristics and an inferior prognosis. By using whole-genome sequencing (WGS) and whole-exome sequencing (WES) data, we found strikingly different mutation profiles between upper aerodigestive tract (UAT)- and NUAT-NKTCL patients, with the latter group exhibiting significantly higher genomic instability. In the NUAT-NKTCL cohort, 128 patients received frontline P-GEMOX chemotherapy, 37 of whom also received anti-PD-1 immunotherapy. The application of anti-PD-1 significantly improved progression-free survival (3-year PFS rate 53.9% versus 17.0%, P = 0.009) and overall survival (3-year OS rate 63.7% versus 29.2%, P = 0.01) in the matched NUAT-NKTCL cohort. WES revealed frequent mutations involving immune regulation and genomic instability in immunochemotherapy responders. Our study showed distinct clinical characteristics and mutational profiles in NUAT-NKTCL compared with UAT patients and suggested adding anti-PD-1 immunotherapy in front-line treatment of NUAT-NKTCL. Further studies are needed to validate the efficacy and related biomarkers for immunochemotherapy proposed in this study.


Assuntos
Linfoma Extranodal de Células T-NK , Humanos , Linfoma Extranodal de Células T-NK/genética , Linfoma Extranodal de Células T-NK/terapia , Linfoma Extranodal de Células T-NK/diagnóstico , Genômica , Imunoterapia , Instabilidade Genômica , Células Matadoras Naturais/patologia
18.
J Gastrointest Oncol ; 14(3): 1546-1559, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37435228

RESUMO

Background: This study aimed to understand the mechanism of action of deoxythymidylate kinase (DTYMK) and its effect on the prognosis of patients with pancreatic cancer. So as to provide better reference value for improving the clinical management of pancreatic cancer patients. Methods: First, The Cancer Genome Atlas (TCGA) database was employed to identify DTYMK as a differentially expressed gene and to further confirm its expression and its association with the prognosis of pancreatic adenocarcinoma (PAAD) patients. Furthermore, Cox Law of Return is used for multi factor analysis. By constructing a multi factor regression model, a nomogram is constructed according to the contribution of each influencing factor in the model to the outcome variables, The GeneMania and STRING databases served as the basis for investigating the protein-gene interaction network. Moreover, to understand the correlation between DTYMK and immune cells, the TIMER and TCGA databases were explored. Then, Gene Set Enrichment Analysis (GSEA) was performed to investigate potential mechanisms of action. TargetScan was used to identify the miRNAs binding to the 3'UTR of DTYMK mRNA, and starBase was used to verify a possible link between candidate miRNAs and DTYMK. In parallel, the expression of these potential miRNAs in PAAD and their correlation with prognosis was validated through the TCGA database. Results: PAAD patients were observed to have high overall survival (OS), progression free interval (PFI), and disease-specific survival (DSS) with reduced DTYMK expression. Data from the TIMER database show that DTYMK expression inversely correlated with the infiltration levels of most immune cells. GSEA results suggested that DTYMK has a role in cell senescence, DNA repair, pyrimidine metabolism, MYC activation, TP53 control of cell cycle arrest, apoptosis, and the MAPK6/MAPK4 pathway, all of which might influence the biological processes of PAAD. Conclusions: Reduced DTYMK expression may be considered a novel prognostic biomarker for PAAD patients, associated with improved OS, DSS, and PFI. Immune escape may play an important facilitative role. Moreover, we found that miR-491-5p may negatively regulate DTYMK and participate in cell cycle arrest through TP53 to promote pancreatic cancer progression.

19.
Cancer Med ; 12(3): 3812-3829, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36812125

RESUMO

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a non-Hodgkin lymphoma with high mortality rates. Small nucleolar RNAs (snoRNAs) are tumor-specific biological markers, but there are few studies on the role of snoRNAs in DLBCL. MATERIALS AND METHODS: Survival-related snoRNAs were selected to construct a specific snoRNA-based signature via computational analyses (Cox regression and independent prognostic analyses) to predict the prognosis of DLBCL patients. To assist in clinical applications, a nomogram was built by combining the risk model and other independent prognostic factors. Pathway analysis, gene ontology analysis, transcription factor enrichment, protein-protein interactions, and single nucleotide variant analysis were used to explore the potential biological mechanisms of co-expressed genes. RESULTS: Twelve prognosis-correlated snoRNAs were selected from the DLBCL patient cohort of microarray profiles, and a three-snoRNA signature consisting of SNORD1A, SNORA60, and SNORA66 was constructed. DLBCL patients could be divided into high-risk and low-risk cohorts using the risk model, and the high-risk group and activated B cell-like (ABC) type DLBCL were linked with disappointing survival. In addition, SNORD1A co-expressed genes were inseparably linked to the biological functions of the ribosome and mitochondria. Potential transcriptional regulatory networks have also been identified. MYC and RPL10A were the most mutated SNORD1A co-expressed genes in DLBCL. CONCLUSION: Put together, our findings explored the potential biological effects of snoRNAs in DLBCL, and provided a new predictor for DLBCL prediction.


Assuntos
Linfoma Difuso de Grandes Células B , RNA Nucleolar Pequeno , Humanos , Prognóstico , Linfócitos B/patologia , Nomogramas , Biomarcadores Tumorais/genética
20.
Medicine (Baltimore) ; 102(43): e35527, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37904460

RESUMO

BACKGROUND: Neuralgic amyotrophy (NA) is a clinically acute or subacute disease. To study the characteristics of brachial plexus magnetic resonance neurography (MRN) in patients with NA, and to explore the clinical application value of MRN combined with electromyography (EMG) in the diagnosis of NA. METHODS: Brachial plexus MRN images of 32 patients with NA were retrospectively analyzed, and their characteristics were investigated. The accuracy, sensitivity and specificity of MRN, EMG, and the combination of the 2 methods for NA diagnosis were compared. RESULTS: Among the 32 patients with NA, 28 (87.5%) cases of unilateral brachial plexus involvement, 18 (56.3%) cases of multiple nerve roots involvement. In 10 cases, C5 nerve roots were involved alone, and in 9 cases, C5 to C6 nerve roots were involved together. The T2 signal intensity of the affected nerve increased, and 19 cases showed thickened and smooth nerve root edges. Twelve cases showed uneven thickening and segmental stenosis of the involved nerve roots. The diagnostic accuracy, sensitivity, and specificity of MRN for NA were higher than those of EMG. Combining MRN and EMG could improve the sensitivity and specificity of diagnosis. CONCLUSION: The main feature of MRN in patients with NA was that it was unilateral brachial plexus asymmetric involvement. The diagnostic effect of MRN was better than that of EMG. The combined diagnosis of MRN and EMG can help clinicians diagnose NA accurately.


Assuntos
Neurite do Plexo Braquial , Neuropatias do Plexo Braquial , Plexo Braquial , Humanos , Neurite do Plexo Braquial/diagnóstico por imagem , Estudos Retrospectivos , Plexo Braquial/diagnóstico por imagem , Neuropatias do Plexo Braquial/diagnóstico , Sensibilidade e Especificidade , Espectroscopia de Ressonância Magnética , Imageamento por Ressonância Magnética/métodos
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