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BACKGROUND: Uterine corpus endometrial carcinoma (UCEC) is a prevalent gynecologic malignancy with a favorable prognosis if detected early. However, there is a lack of accurate and reliable early detection tests for UCEC. This study aims to develop a precise and non-invasive diagnostic method for UCEC using circulating cell-free DNA (cfDNA) fragmentomics. METHODS: Peripheral blood samples were collected from all participants, and cfDNA was extracted for analysis. Low-coverage whole-genome sequencing was performed to obtain cfDNA fragmentomics data. A robust machine learning model was developed using these features to differentiate between UCEC and healthy conditions. RESULTS: The cfDNA fragmentomics-based model showed high predictive power for UCEC detection in training (n = 133; AUC 0.991) and validation cohorts (n = 89; AUC 0.994). The model manifested a specificity of 95.5% and a sensitivity of 98.5% in the training cohort, and a specificity of 95.5% and a sensitivity of 97.8% in the validation cohort. Physiological variables and preanalytical procedures had no significant impact on the classifier's outcomes. In terms of clinical benefit, our model would identify 99% of Chinese UCEC patients at stage I, compared to 21% under standard care, potentially raising the 5-year survival rate from 84 to 95%. CONCLUSION: This study presents a novel approach for the early detection of UCEC using cfDNA fragmentomics and machine learning showing promising sensitivity and specificity. Using this model in clinical practice could significantly improve UCEC management and control, enabling early intervention and better patient outcomes. Further optimization and validation of this approach are warranted to establish its clinical utility.
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Ácidos Nucleicos Livres , Detecção Precoce de Câncer , Neoplasias do Endométrio , Humanos , Feminino , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/sangue , Neoplasias do Endométrio/genética , Pessoa de Meia-Idade , Ácidos Nucleicos Livres/sangue , Detecção Precoce de Câncer/métodos , Idoso , Aprendizado de Máquina , Adulto , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Sensibilidade e EspecificidadeRESUMO
Demand for ultra-small, inexpensive, and high-accurate 3D shape measurement devices is growing rapidly, especially in the industrial and consumer electronics sectors. Phase shifting profilometry (PSP) is a powerful candidate due to its advantages of high accuracy, great resolution, and insensitivity to ambient light. As a key component in PSP, the projector used to generate the phase-shifting sinusoidal fringes must be ultra-small (several millimeters), low-cost, and simple to control. However, existing projection methods make it difficult to meet these requirements simultaneously. In this paper, we present a modern technique that can be used to fabricate the desired projector. A specifically designed device based on segmented liquid crystal display (SLCD) technology is used to display the projected patterns, and a cylindrical lens is used as the projection lens. The SLCD device can display four sets of specific filled binary patterns, each yielding a sinusoidal fringe, and all four sinusoidal fringes satisfy the four-step phase shift relation. 3D shape measurement experiments verify the performance of the projector. Considering that the size of SLCD devices can be reduced to a few millimeters, the proposed technique can be easily used to manufacture ultra-small, low-cost, and simple-to-control PSP projectors.
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OBJECTIVE: To evaluate the feasibility, safety and efficacy of concurrent simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with nimotuzumab in the treatment of locally advanced esophageal squamous cell cancer (ESCC). METHODS: Eligible patients were histologically proven to have locally advanced ESCC, and were unable to tolerate or refuse concurrent chemoradiotherapy (CCRT). Enrolled patients underwent concurrent SIB-IMRT in combination with nimotuzumab. SIB-IMRT: For the planning target volume of clinical target volume (PTV-C), the prescription dose was 50.4 Gy/28fractions, 1.8 Gy/fraction, 5fractions/week, concurrently, the planning target volume of gross tumor (PTV-G) undergone an integrated boost therapy, with a prescription dose of 63 Gy/28fractions, 2.25 Gy/fraction, 5 fractions/week. Nimotuzumab was administered concurrently with radiotherapy, 200 mg/time, on D1, 8, 15, 22, 29, and 36, with a total accumulation of 1200 mg through intravenous infusion. The primary endpoint of the study was the safety and efficacy of the combined treatment regimen, and the secondary endpoints were 1-year, 2-year, and 3-year local control and survival outcomes. RESULTS: (1) From December 2018 to August 2021, 35 patients with stage II-IVA ESCC were enrolled and 34 patients completed the full course of radiotherapy and the intravenous infusion of full-dose nimotuzumab. The overall completion rate of the protocol was 97.1%. (2) No grade 4-5 adverse events occurred in the entire group. The most common treatment-related toxicity was acute radiation esophagitis, with a total incidence of 68.6% (24/35). The incidence of grade 2 and 3 acute esophagitis was 25.7% (9/35) and 17.1% (6/35), respectively. The incidence of acute radiation pneumonitis was 8.6% (3/35), including one case each of Grades 1, 2, and 3 pneumonitis. Adverse events in other systems included decreased blood cells, hypoalbuminemia, electrolyte disturbances, and skin rash. Among these patients, five experienced grade 3 electrolyte disturbances during the treatment period (three with grade 3 hyponatremia and two with grade 3 hypokalemia). (3) Efficacy: The overall CR rate was 22.8%, PR rate was 71.4%, ORR rate was 94.2%, and DCR rate was 97.1%.(4) Local control and survival: The 1-, 2-, and 3-year local control (LC) rate, progression-free survival(PFS) rate, and overall survival(OS) rate for the entire group were 85.5%, 75.4%, and 64.9%; 65.7%, 54.1%, and 49.6%; and 77.1%, 62.9%, and 54.5%, respectively. CONCLUSIONS: The combination of SIB-IMRT and nimotuzumab for locally advanced esophageal cancer demonstrated good feasibility, safety and efficacy. It offered potential benefits in local control and survival. Acute radiation esophagitis was the primary treatment-related toxicity, which is clinically manageable. This comprehensive treatment approach is worthy of further clinical exploration (ChiCTR1900027936).
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Anticorpos Monoclonais Humanizados , Quimiorradioterapia , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Radioterapia de Intensidade Modulada , Humanos , Masculino , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Feminino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/radioterapia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Radioterapia de Intensidade Modulada/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/tratamento farmacológico , Idoso , Quimiorradioterapia/métodos , Adulto , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/administração & dosagem , Resultado do TratamentoRESUMO
PURPOSE: In brain development, Myelination is the characteristic feature of white matter maturation, which plays an important role in efficient information transmitting. The white matter abnormality has been reported to be associated with self-limited epilepsy with centrotemporal spikes (SeLECTS). This study aimed to detect the altered white matter region in the SeLECTS patients by the combination of diffusion tensor imaging (DTI) and quantitative susceptibility mapping (QSM) technique. METHODS: 27 children with SeLECTS and 23 age- and gender-matched healthy children were enrolled. All participants were scanned with 3.0-T MRI to acquire the structure, diffusion and susceptibility-weighted data. The susceptibility and diffusion weighted data were processed to obtain quantitative susceptibility map and fraction anisotropy (FA) map. Then voxel-wise tract-based spatial statistics (TBSS) were used to analyze quantitative susceptibility and FA data. RESULTS: Both DTI and QSM revealed extensive white matter alterations in the frontal, parietal, and temporal lobes in SeLECTS patients. The overlapped region of DTI and QSM analyses was located in the fiber tracts of the corona radiata. The FA values in this overlapped region were negatively correlated with the magnetic susceptibility values. CONCLUSION: Our results suggest that TBSS-based QSM can be employed as a novel approach for characterizing alterations in white matter in SeLECTS. And the combination of QSM and DTI can provide a more comprehensive evaluation of white matter integrity by utilizing different biophysical features.
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Imagem de Tensor de Difusão , Substância Branca , Humanos , Imagem de Tensor de Difusão/métodos , Feminino , Masculino , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Criança , Epilepsia Rolândica/diagnóstico por imagem , Epilepsia Rolândica/fisiopatologia , Estudos de Casos e Controles , Anisotropia , Mapeamento Encefálico/métodos , Pré-Escolar , AdolescenteRESUMO
PURPOSE: This article aims to analyze pediatric meningioma's imaging characteristics, especially those in unusual locations. METHODS: Pediatric patients with pathologically confirmed meningiomas at our hospital from January 2010 to January 2024 were enrolled. Meningiomas located in the cerebral convexity, parasagittal falcine region, anterior skull base, middle skull base, sphenoid ridge, cerebellopontine angle (CPA), olfactory groove, or juxtasella were considered in usual locations. Meningiomas found in other areas were considered in unusual locations. Clinical information, pathology results, and imaging features of pediatric meningiomas in usual and usual locations were analyzed and compared. RESULTS: A total of 18 patients (19 meningiomas) were enrolled, including 14 males and 4 females, with an average age of 14 years (ranging from 6 to 18 years). A total of 12 (63.2%) meningiomas were in the unusual location, including four (33.3%) were intraparenchymal, four (33.3%) were intraventricular, two (16.7%) were intraosseous, one (8.3%) case was in the paranasal sinus, and one (8.3%) was intraspinal. The meningiomas in unusual locations usually lacked the meningeal tail sign, and the misdiagnosis rate on preoperative imaging was significantly higher than that of meningiomas in usual locations. CONCLUSION: Pediatric meningiomas are prone to occur in unusual locations. When they occur in usual locations, they often lack typical radiographic features of meningiomas, leading to potential misdiagnosis before surgery. Recognition of the imaging characteristics of meningiomas in unusual locations in children may facilitate accurate preoperative imaging diagnosis.
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OBJECTIVES: To report the 10-year survival rate and prognostic factors of pulmonary arterial hypertension associated with CTD (CTD-PAH) patients, to compare treatment and survival between patients enrolled before and after 2015, and to validate the discrimination of the recommended four-strata model in predicting 10-year survival at follow-up in Chinese CTD-PAH patients. METHODS: This study was derived from a Chinese national multicentre prospective registry study from 2009 to 2019. Medical records were collected at baseline and follow-up, including PAH-targeted therapy and binary therapy (both CTD and PAH-targeted therapy). RESULTS: A total of 266 CTD-PAH patients were enrolled and the 10-year survival rate was 59.9% (median follow-up time: 4.85 years). Underlying CTD (SSc), baseline 6-min walking distance and SaO2 were independent risk factors for 10-year survival. The proportion of patients receiving PAH-targeted combination therapy increased from 10.1% (2009-2014) to 26.5% (2015-2019) and that of binary therapy increased from 14.8% to 35%. The 1-year survival rate increased from 89.8% (2009-2014) to 93.9%, and the 3-year survival rate increased from 80.1% (2009-2014) to 86.5% (both P > 0.05). The four-strata strategy performed well in predicting 10-year survival at follow-up (C-index = 0.742). CONCLUSION: The 10-year survival rate of CTD-PAH patients was reported for the first time. The 10-year prognosis was poor, but there was a tendency for more standardized treatment and better survival in patients enrolled after 2015. The recommended four-strata model at follow-up can effectively predict 10-year survival in CTD-PAH patients.
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Doenças do Tecido Conjuntivo , Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Humanos , Hipertensão Arterial Pulmonar/etiologia , Hipertensão Arterial Pulmonar/complicações , Doenças do Tecido Conjuntivo/complicações , Prognóstico , Hipertensão Pulmonar Primária Familiar/complicações , Sistema de RegistrosRESUMO
Cerebral ischemia results in loss of cerebral blood flow, which contributes to neuronal damage, neurocognitive impairment, as well as learning and memory difficulties. Although reperfusion is necessary to restore the blood supply to the brain, it also leads to several detrimental effects on the brain. The purpose of this study was to assess the effects of ulinastatin (UTI) on preventing focal cerebral ischemia/reperfusion-induced injury (FCIRI). First, a rat model of FCIRI was established and treated with UTI. The effects of UTI on FCIRI in rats were evaluated using Morris water maze assay, triphenyl tetrazolium chloride staining, TUNEL, western blot assay, and enzyme-linked immunosorbent assay analysis. UTI was found to improve the learning memory ability, reduce infarction area, inhibit apoptosis and decrease inflammation in FCIRI rats. Messenger RNA microarray analysis of hippocampal tissues revealed that suppressor of cytokine signalling-1 (SOCS1) was the downstream target of UTI in FCIRI. SOCS1 depletion impaired the protective effect of UTI on FCIRI in rats. SOCS1 blocked the activation of the JAK2/STAT3 pathway. JAK2 inhibitor caused the JAK2/STAT3 pathway deficit, hence reversing the effect of sh-SOCS1 on FCIRI in rats. Taken together, our results demonstrate that UTI alleviated FCIRI in rats, which was, to some extent, related to SOCS1-mediated JAK2/STAT3 pathway.
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Isquemia Encefálica , Traumatismo por Reperfusão , Animais , Ratos , Inflamação , Neurônios , Isquemia Encefálica/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Proteína 1 Supressora da Sinalização de Citocina/genética , Janus Quinase 2RESUMO
AIMS: This study aimed to identify mechanisms of drug resistance to the combination of vemurafenib, irinotecan, and cetuximab (VIC) in BRAFV600E metastatic colorectal cancer (mCRC). METHODS: Forty-one patients with BRAFV600E mCRC from July 2018 and June 2020 were evaluated, with tissue and/or plasma samples collected. We profiled tissue and plasma samples using whole-exome sequencing and targeted sequencing of 425 cancer-relevant genes. Clinical cohort analysis from published studies was performed to consolidate our findings. RESULTS: BRAF mutant in baseline plasma and its dynamics are significantly associated with VIC-related response, and concurrent RNF43 mutation significantly sensitises tumour to VIC treatment. VIC resistance frequently involves genes in PI3K, MAPK pathway, and several novel resistance mechanisms such as TGFBR2 and SMAD4 mutations, and copy-number gains in PTK2, MYC, and GATA6 have been identified. We also firstly describe acquired altered genes in DNA damaging repair pathway, occurring in 33 % of patients after VIC treatment, and particularly, patients with this pre-treatment resistance subclones developed inferior responses, along with higher tumour mutation burden both at baseline and progression plasma. CONCLUSION: Analysis of ctDNA can provide novel insights into molecular resistance mechanisms to VIC in BRAFV600E mCRC patients, allowing accurate guidance for clinicians in personalised treatment strategies.
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DNA Tumoral Circulante , Neoplasias Colorretais , Resistencia a Medicamentos Antineoplásicos , Humanos , Cetuximab/farmacologia , Cetuximab/uso terapêutico , DNA Tumoral Circulante/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Irinotecano/farmacologia , Irinotecano/uso terapêutico , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Vemurafenib/uso terapêuticoRESUMO
Cell-free DNA (cfDNA), as a non-invasive approach, has been introduced in a wide range of applications, including cancer diagnosis/ monitoring, prenatal testing, and transplantation monitoring. Yet, studies of cfDNA fragmentomics in physiological conditions are lacking. In this study, we aim to explore the correlation of fragmentation patterns of cfDNA with blood biochemical and hematological parameters in healthy individuals. We addressed the impact of physiological variables and abnormal blood biochemical and hematological parameters on cfDNA fragment size distribution. We also figured and validated that hematological inflammation markers, including leukocyte, lymphocyte, neutrophil, and platelet distribution width as well as aspartate transaminase levels were significantly correlated with the genome-wide cfDNA fragmentation pattern. Our findings suggest that cfDNA fragmentation profiles were associated with physiological parameters related to cardiovascular risk factors, inflammatory response and hepatocyte injury, which may provide insights for further research on the potential role of cfDNA fragmentation in diagnosis and monitor of several disease.
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Ácidos Nucleicos Livres , Humanos , Fragmentação do DNARESUMO
Investigating the contributing factors of career adaptability has always been an important topic in the field of vocational psychology research. From the perspective of person-environment interaction, this study introduced the role accumulation theory into the researches of career adaptability. Using a sample of 379 Chinese college students (mean age = 20.36 years, SD = 1.67), a model of role accumulation affecting college students' career adaptability was constructed, and the parallel mediating mechanisms of self-efficacy and social support were also discussed. Participants filled out questionnaires regarding role accumulation, self-efficacy, social support, and career adaptability. The results of structural equation modeling (SEM) showed that: (1) Role accumulation positively predicted career adaptability in college students; (2) Role accumulation also indirectly predicted career adaptability through self-efficacy and social support. The present study is the first to validate the psychological pathways linking role accumulation to career adaptability via self-efficacy and social support. The contribution of this study to the literature is to provide a new perspective that can clarify the predictors of career adaptability. In addition, for educational administrators and career practitioners, targeting role accumulation is valuable for developing college students' career adaptability.
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BACKGROUND: Free circular RNAs(circRNAs) escaping from primary lesion of cancer to brain are strictly regulated by blood-brain barrier and therefore cerebrospinal fluid (CSF) circRNAs have potential advantage in exploring biomarkers and mechanism of brain metastasis in lung cancer. METHODS: We collected paired cerebrospinal fluid, plasma and tumor tissues from 21 lung adenocarcinoma (ADC) patients with brain metastases (BM) and performed RNA sequencing. RESULTS: Compared to tumor tissue and plasma, circRNAs in CSF were characterized by lower number of spieces but higher abundance. Notably, CSF-circRNAs displayed high heterogeneity among different BM lung ADC patients. A total of 60 CSF-circRNAs was identified and associated with shorten overall survival. The circRNA-miRNA-mRNA network analysis revealed that the 60 CSF-circRNAs involved in cancer-associated pathways, and five of them showed strong association with WNT signaling pathway. Validation by RT-PCR of CSF and in vitro experiments of the five candidate circRNAs support their potential roles in cell proliferation and invasion. CONCLUSIONS: In summary, our results depicted the heterogenous CSF-circRNAs profiles among BM lung ADC and implied that CSF-circRNAs may be promising prognosis-related biomarkers.
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Adenocarcinoma de Pulmão , Neoplasias Encefálicas , Neoplasias Pulmonares , MicroRNAs , Adenocarcinoma de Pulmão/genética , Neoplasias Encefálicas/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , RNA Circular/genéticaRESUMO
BACKGROUND AND OBJECTIVE: Nationally representative reports on the characteristics and long-term survival of pulmonary arterial hypertension (PAH) from developing countries are scarce. The applicability of the current main risk stratifications and the longitudinal changes in goal-oriented treatments have yet to be elucidated in real-world settings. Therefore, we aimed to provide insights into the characteristics, goal-oriented treatments and survival of PAH in China and to explore the applicability of the main risk stratifications in our independent cohort. METHODS: PAH patients were consecutively enrolled from a national prospective multicentre registry. Data on baseline, follow-up re-evaluation and therapeutic changes were collected. RESULTS: A total of 2031 patients were enrolled, with congenital heart disease (CHD)-PAH (45.2%) being the most common aetiology. The mean age was 35 ± 12 years, and 76.2% were females. At baseline, approximately 20% of the patients with intermediate or high risk received combination treatment. At follow-up, approximately half of the re-evaluated patients did not achieve low-risk profiles, and even among patients who received combination therapy at baseline, 4% of them still worsened. The rate of combination therapy increased significantly from 6.7% before 2015 to 35.5% thereafter. The main risk assessment tools demonstrated good performance for predicting survival both at baseline and at follow-up. CONCLUSION: Chinese PAH patients show both similar and distinct features compared to other countries. Current main risk stratifications can significantly discriminate patients at different risk levels. There were still many patients not achieving low-risk profiles at follow-up, indicating more aggressive treatment should be implemented to optimize the goal-oriented treatment strategy.
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Cardiopatias Congênitas , Hipertensão Arterial Pulmonar , Adulto , Hipertensão Pulmonar Primária Familiar , Feminino , Objetivos , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Adulto JovemRESUMO
Cadmium (Cd) pollution has detrimental effects on the ecological environment and human health. Currently, phytoremediation is considered an environmentally friendly way to remediate Cd pollution. The application of transgenic plants to remediate soil pollution is a new technology that has emerged in recent years. In this study, PyWRKY75 was isolated and cloned from Populus yunnanensis, and the functionality of PyWRKY75 in woody plants (poplar) under Cd stress was verified. The increase in plant height of the OE-41 line (overexpression poplar) was 33.2% higher than that of the wild type (WT). Moreover, PyWRKY75 significantly promoted the absorption and accumulation of Cd in poplar, which increased by 51.32% in the OE-41 line when compared with the WT. The chlorophyll content of transgenic poplar leaves was higher than that of the WT, which reflected a protective mechanism of PyWRKY75. Other antioxidants, such as POD, SOD, CAT, APX, AsA, GSH and PCs, also made the transgenic poplars more tolerant to Cd, and they behaved differently in roots, stems and leaves. In general, PyWRKY75 played a potential role in regulating plant tolerance to Cd stress. This study provides a scientific basis and a new type of modified poplar for Cd pollution remediation.
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Populus , Poluentes do Solo , Fatores de Transcrição , Cádmio/toxicidade , Folhas de Planta , Raízes de Plantas/genética , Populus/genética , Poluentes do Solo/toxicidade , Fatores de Transcrição/genéticaRESUMO
A boy, aged 5 years, attended the hospital due to progressive psychomotor regression for 2.5 years. Motor function regression was the main manifestation in the early stage, and brain MRI and whole-exome sequencing (WES) of the family showed no abnormalities. After the age of 4 years and 9 months, the boy developed cognitive function regression, and brain MRI showed cerebellar atrophy. The reanalysis of WES results revealed a compound heterozygous mutation, [NM_000520, c.784C>T(p.His262Tyr]), c.1412C>T(p.Pro471Leu)], in the HEXA gene. The enzyme activity detection showed a significant reduction in the level of ß-hexosaminidase encoded by this gene. The boy was diagnosed with juvenile Tay-Sachs disease (TSD). TSD has strong clinical heterogeneity, and cerebellar atrophy may be an important clue for the diagnosis of juvenile TSD. The reanalysis of genetic data when appropriate based on disease evolution may improve the positive rate of WES.
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Doença de Tay-Sachs , Atrofia , Humanos , Imageamento por Ressonância Magnética , Masculino , Mutação , Doença de Tay-Sachs/diagnóstico , Doença de Tay-Sachs/genéticaRESUMO
Patients with triple-negative breast cancer have a poor prognosis as only a few efficient targeted therapies are available. Cancer cells are characterized by their unregulated proliferation and require large amounts of nucleotides to replicate their DNA. One-carbon metabolism contributes to purine and pyrimidine nucleotide synthesis by supplying one carbon atom. Although mitochondrial one-carbon metabolism has recently been focused on as an important target for cancer treatment, few specific inhibitors have been reported. In this study, we aimed to examine the effects of DS18561882 (DS18), a novel, orally active, specific inhibitor of methylenetetrahydrofolate dehydrogenase (MTHFD2), a mitochondrial enzyme involved in one-carbon metabolism. Treatment with DS18 led to a marked reduction in cancer-cell proliferation; however, it did not induce cell death. Combinatorial treatment with DS18 and inhibitors of checkpoint kinase 1 (Chk1), an activator of the S phase checkpoint pathway, efficiently induced apoptotic cell death in breast cancer cells and suppressed tumorigenesis in a triple-negative breast cancer patient-derived xenograft model. Mechanistically, MTHFD2 inhibition led to cell cycle arrest and slowed nucleotide synthesis. This finding suggests that DNA replication stress occurs due to nucleotide shortage and that the S-phase checkpoint pathway is activated, leading to cell-cycle arrest. Combinatorial treatment with both inhibitors released cell-cycle arrest, but induced accumulation of DNA double-strand breaks, leading to apoptotic cell death. Collectively, a combination of MTHFD2 and Chk1 inhibitors would be a rational treatment option for patients with triple-negative breast cancer.
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Aminoidrolases/antagonistas & inibidores , Quinase 1 do Ponto de Checagem/antagonistas & inibidores , Inibidores Enzimáticos/uso terapêutico , Metilenotetra-Hidrofolato Desidrogenase (NADP)/antagonistas & inibidores , Enzimas Multifuncionais/antagonistas & inibidores , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Administração Oral , Aminoidrolases/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quinase 1 do Ponto de Checagem/metabolismo , Quimioterapia Combinada , Inibidores Enzimáticos/administração & dosagem , Feminino , Humanos , Metilenotetra-Hidrofolato Desidrogenase (NADP)/metabolismo , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Enzimas Multifuncionais/metabolismo , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/enzimologia , Neoplasias de Mama Triplo Negativas/patologia , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
OBJECTIVES: Right ventricular (RV) function is considered the major determinant of prognosis in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this meta-analysis was to evaluate RV remodelling and function following balloon pulmonary angioplasty (BPA) in patients with inoperable CTEPH or persistent/recurrent pulmonary hypertension (PH) after pulmonary endarterectomy (PEA). METHODS: We reviewed all studies evaluating RV function by cardiac magnetic resonance (CMR) and/or echocardiography pre- and post-BPA from PubMed/Medline prior to 15 December 2019. Ten (299 patients) of the 29 studies retrieved met the inclusion criteria: 5 CMR and 5 echocardiography studies. The systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines. RESULTS: Pooled data from CMR studies revealed BPA resulted in a significantly decreased RV end-diastolic volume index (weighted mean difference (WMD) - 28.33 ml/m2, p < 0.00001) and RV end-systolic volume index (WMD - 29.06 ml/m2, p < 0.00001) accompanied by an increased RV ejection fraction (RVEF, WMD 8.97%, p < 0.00001). Data from the echocardiography studies showed BPA resulted in decreased RV basal diameter (WMD - 0.37 cm, p = 0.0009) and an increase of RV fractional area change (WMD 5.97 %, p = 0.003), but improvements of tricuspid annular plane systolic excursion (TAPSE) and S' were not significant. CONCLUSIONS: BPA improves RVEF and decreases RV volumes in patients with inoperable CTEPH or persistent/recurrent PH after PEA. KEY POINTS: ⢠Balloon pulmonary angioplasty improves RVEF and decreases RV volumes in patients with inoperable CTEPH or persistent/recurrent PH after PEA.
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Angioplastia com Balão , Hipertensão Pulmonar , Embolia Pulmonar , Disfunção Ventricular Direita , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/terapia , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/terapia , Função Ventricular Direita , Remodelação VentricularRESUMO
Rhabdomyosarcoma (RMS) is a common malignancy in children, but embryonal rhabdomyosarcoma (ERMS) deposits rarely occur in the breast in adults. Therefore, little is known about magnetic resonance imaging (MRI) features of breast metastases from RMS, especially the embryonal type. We reported a case of a 22-year-old woman who was diagnosed with ERMS at left foot 2 years ago and accepted operation and chemotherapy. She was confirmed to have breast metastases from the left foot. Successive imaging examinations were performed 3 months apart. Breast ultrasound indicated a benign lesion, and further examination did not reveal any bone metastases. However, predominant restricted diffusion and rim contrast enhancement on MRI combined with the patient's medical history suggested a malignancy of BI-RADS 5. After 3 months, breast ultrasound revealed masses detected last time became larger and lobulated. In addition, internal heterogeneous intensity and rim contrast enhancement with restricted diffusion were revealed on MRI. We speculated that typical MRI findings of breast metastases from RMS may include iso- to hypointensity on T1WI, heterogeneous hyperintensity on T2WI, and circular enhancement with restricted diffusion. Moreover, mild peritumoral edema, rapid expansion of necrosis, and ascending time-intensity curve detected on MRI may be features of the ERMS type.
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Neoplasias da Mama , Rabdomiossarcoma Embrionário , Rabdomiossarcoma , Adulto , Mama/patologia , Neoplasias da Mama/patologia , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Rabdomiossarcoma/patologia , Rabdomiossarcoma Embrionário/diagnóstico por imagem , Rabdomiossarcoma Embrionário/patologia , Adulto JovemRESUMO
BACKGROUND: At present, there is no generally accepted comprehensive prognostic risk prediction model for medically treated chronic thromboembolic pulmonary hypertension (CTEPH) patients. METHODS: Consecutive medically treated CTEPH patients were enrolled in a national multicenter prospective registry study from August 2009 to July 2018. A multivariable Cox proportional hazards model was utilized to derive the prognostic model, and a simplified risk score was created thereafter. Model performance was evaluated in terms of discrimination and calibration, and compared to the Swedish/COMPERA risk stratification method. Internal and external validation were conducted to validate the model performance. RESULTS: A total of 432 patients were enrolled. During a median follow-up time of 38.73 months (IQR: 20.79, 66.10), 94 patients (21.8%) died. The 1-, 3-, and 5-year survival estimates were 95.5%, 83.7%, and 70.9%, respectively. The final model included the following variables: the Swedish/COMPERA risk stratum (low-, intermediate- or high-risk stratum), pulmonary vascular resistance (PVR, ≤ or > 1600 dyn·s/cm5), total bilirubin (TBIL, ≤ or > 38 µmol/L) and chronic kidney disease (CKD, no or yes). Compared with the Swedish/COMPERA risk stratification method alone, both the derived model [C-index: 0.715; net reclassification improvement (NRI): 0.300; integrated discriminatory index (IDI): 0.095] and the risk score (C-index: 0.713; NRI: 0.300; IDI: 0.093) showed improved discriminatory power. The performance was validated in a validation cohort of 84 patients (C-index = 0.707 for the model and 0.721 for the risk score). CONCLUSIONS: A novel risk stratification strategy can serve as a useful tool for determining prognosis and guide management for medically treated CTEPH patients. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT01417338).
Assuntos
Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/fisiopatologia , Insuficiência Renal Crônica/complicações , Medição de Risco/métodos , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Hipertensão Pulmonar/terapia , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Prognóstico , Estudos Prospectivos , Sistema de Registros , Análise de Sobrevida , Resistência VascularRESUMO
Growing skull fracture (GSF) is a rare complication of pediatric head trauma. It usually arises from a linear fracture with an underlying dural tear, which results in herniation of the intracranial contents. In rare cases, the herniated intracranial contents can be restricted in the diploe, resulting in an expanded diploic cavity. If there is brain parenchyma herniating into the expanded diploic cavity, the condition is termed as intradiploic encephalocele (IE). Here we present a peculiar pediatric occipital GSF case that resulted from the silent progression of a linear fracture with a small brain herniation into the widened fracture finally leading to an IE after approximately 7 years. Detailed imaging findings from the early injury to the late phase of the disease were provided to record this natural process. To the best of our knowledge, this is the first case providing the imaging data of early injury before developing into IE.
Assuntos
Traumatismos Craniocerebrais , Meningite , Fraturas Cranianas , Encéfalo , Criança , Encefalocele/diagnóstico por imagem , Encefalocele/etiologia , Encefalocele/cirurgia , Humanos , Crânio/diagnóstico por imagem , Fraturas Cranianas/complicações , Fraturas Cranianas/diagnóstico por imagem , Fraturas Cranianas/cirurgiaRESUMO
OBJECTIVE: Reportedly, nestin was re-expressed in proliferative synthetic-type pulmonary artery smooth muscle cells (PASMCs) and obligatory for PASMC proliferation in pulmonary arterial hypertension (PAH). Accordingly, nestin is increased in pulmonary vascular lesions of congenital heart disease (CHD)-associated PAH patients. We tested the hypothesis whether nestin was re-expressed in proliferative synthetic-type PASMCs and associated with pulmonary vascular remodeling in CHD-PAH. MATERIALS AND METHODS: Nestin expression was tested using lung tissues from CHD-PAH patients and monocrotaline (MCT) plus aortocaval (AV) shunt-induced PAH rats, human PASMCs (HPASMCs), and pulmonary artery endothelial cells (PAECs) and PASMCs from MCT-AV-induced PAH rats. The role and possible mechanism of nestin on HPASMC proliferation, apoptosis, cell cycle and migration were investigated by assays of CCK-8, EdU, TUNEL, flow cytometry, transwell chamber and immunoblotting assays. RESULTS: Nestin was solely expressed in proliferative synthetic-type PASMCs, but rarely detected in PAECs. Nestin was barely detected in normal pulmonary arterioles and occlusive pulmonary vascular lesions. Its expression was robustly increased in developing pulmonary vasculature, but returned to normal levels at the late stage of pulmonary vascular remodeling in lung tissues from CHD-PAH patients and MCT-AV-induced PAH rats. Besides, nestin peaks were consistent with the histological features in lung tissues of MCT-AV-induced PAH rats. Moreover, nestin overexpression effectively promoted HPASMC phenotypic transformation, proliferation, apoptosis resistance and migration via enhancing Wnt/ß-catenin activation. CONCLUSIONS: These data indicated that nestin was re-expressed in proliferative synthetic-type PASMCs and might represent a potential marker of pulmonary vascular remodeling in CHD-PAH.