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The fundamental building blocks of the proton-quarks and gluons-have been known for decades. However, we still have an incomplete theoretical and experimental understanding of how these particles and their dynamics give rise to the quantum bound state of the proton and its physical properties, such as its spin1. The two up quarks and the single down quark that comprise the proton in the simplest picture account only for a few per cent of the proton mass, the bulk of which is in the form of quark kinetic and potential energy and gluon energy from the strong force2. An essential feature of this force, as described by quantum chromodynamics, is its ability to create matter-antimatter quark pairs inside the proton that exist only for a very short time. Their fleeting existence makes the antimatter quarks within protons difficult to study, but their existence is discernible in reactions in which a matter-antimatter quark pair annihilates. In this picture of quark-antiquark creation by the strong force, the probability distributions as a function of momentum for the presence of up and down antimatter quarks should be nearly identical, given that their masses are very similar and small compared to the mass of the proton3. Here we provide evidence from muon pair production measurements that these distributions are considerably different, with more abundant down antimatter quarks than up antimatter quarks over a wide range of momenta. These results are expected to revive interest in several proposed mechanisms for the origin of this antimatter asymmetry in the proton that had been disfavoured by previous results4, and point to future measurements that can distinguish between these mechanisms.
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High-quality-factor microring resonators are highly desirable in many applications. Fabricating a microring resonator typically requires delicate instruments to ensure a smooth side wall of waveguides and 100-nm critical feature size in the coupling region. In this work, we demonstrate a new method "damascene soft nanoimprinting lithography" that can create high-fidelity waveguide by simply backfill an imprinted cladding template with a high refractive index polymer core. This method can easily realize high Q-factor polymer microring resonators (e.g., ~5 x 105 around 770 nm wavelength) without the use of any expensive instruments and can be conducted in a normal lab environment. The high Q-factors can be attributed to the residual layer-free feature and controllable meniscus cross-section profile of the filled polymer core. Furthermore, the new method is compatible with different polymers, yields low fabrication defects, enables new functionalities, and allows flexible substrate. These benefits can broaden the applicability of the fabricated microring resonator.
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This Letter presents results of a search for the mixing of a sub-eV sterile neutrino with three active neutrinos based on the full data sample of the Daya Bay Reactor Neutrino Experiment, collected during 3158 days of detector operation, which contains 5.55×10^{6} reactor ν[over ¯]_{e} candidates identified as inverse beta-decay interactions followed by neutron capture on gadolinium. The analysis benefits from a doubling of the statistics of our previous result and from improvements of several important systematic uncertainties. No significant oscillation due to mixing of a sub-eV sterile neutrino with active neutrinos was found. Exclusion limits are set by both Feldman-Cousins and CLs methods. Light sterile neutrino mixing with sin^{2}2θ_{14}â³0.01 can be excluded at 95% confidence level in the region of 0.01 eV^{2}â²|Δm_{41}^{2}|â²0.1 eV^{2}. This result represents the world-leading constraints in the region of 2×10^{-4} eV^{2}â²|Δm_{41}^{2}|â²0.2 eV^{2}.
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PURPOSE: Expression of the programmed death-ligand 1 (PD-L1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) in medullary thyroid carcinoma (MTC) has been controversial and rarely reported. METHODS: Surgical specimens of 190 MTC patients who had initial curative-intent surgery were collected. Immunohistochemistry of PD-L1 and TIM-3 was performed using 22C3 pharmDx (Dako, Carpinteria, CA) and anti-TIM-3 (1:500, ab241332, Abcam). Stained slides were scored using a combined positive score (CPS) with a cutoff of ≥ 1. We established correlations between PD-L1 expression, TIM-3 expression, clinicopathological, and survival data. RESULTS: 13 cases (13/190, 6.84%) were positive for PD-L1 expression, and 42 cases (42/154, 27.27%) for TIM-3 expression. PD-L1 expression was correlated to TIM-3 expression (P = 0.002), but was not related to overall survival (OS) or progression-free survival (PFS). TIM-3 expression was correlated to perineural invasion (P = 0.040). Multivariate Cox analysis showed that lymphovascular invasion (LVI) was independently associated with OS. And tumor size, LVI, and lymph node metastases were significantly associated with PFS. Furthermore, the multivariate logistic analysis showed multifocal status, LVI, pathological T stage and lymph node metastasis were independent risk factors for biochemical recurrence/persistent disease. CONCLUSIONS: We demonstrated that PD-L1 and TIM-3 expression were not frequent in MTC and were not associated with survival prognosis. Our results should be considered when clinical trials of PD-L1 or TIM-3 blockades are implemented.
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Antígeno B7-H1 , Neoplasias da Glândula Tireoide , Humanos , Prognóstico , Imuno-Histoquímica , Antígeno B7-H1/análise , Antígeno B7-H1/metabolismo , Estudos Retrospectivos , Receptor Celular 2 do Vírus da Hepatite A , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/metabolismo , Metástase Linfática , Biomarcadores Tumorais/análiseRESUMO
PURPOSE: Remnant cholesterol (RC) is a contributor to cardiovascular diseases, obesity, diabetes, and metabolic syndrome. However, the specific relationship between RC and bone metabolism remains unexplored. Therefore, we aimed to investigate the relationships of RC with hip bone mineral density (BMD) and the risk of low bone mass. METHODS: Physical examination data was collected from men aged < 60 years as part of the Kailuan Study between 2014 and 2018. The characteristics of the participants were compared between RC quartile groups. A generalized linear regression model was used to evaluate the relationship between RC and hip BMD and a logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for low bone mass. Additional analyses were performed after stratification by body mass index (BMI) (≥ or < 24 kg/m2). Sensitivity analyses were performed by excluding individuals who were taking lipid-lowering therapy or had cancer, cardiovascular diseases, or diabetes. RESULTS: Data from a total of 7,053 participants were included in the analysis. After adjustment for confounding factors, RC negatively correlated with hip BMD (ß = - 0.0079, 95% CI: - 0.0133, - 0.0025). The risk of low bone mass increased from the lowest to the highest RC quartile, with ORs of 1 (reference), 1.09 (95% CI: (0.82, 1.44), 1.35 (95%CI: 1.02, 1.77), and 1.43 (95% CI: 1.09, 1.89) for Q1, Q2, Q3, and Q4, respectively (P for trend = 0.004) in the fully adjusted model. Compared to RC < 0.80 mmol/l group, the risk of low bone mass increased 39% in RC ≥ 0.80 mmol/l group (P < 0.001). The correlation between RC and hip BMD was stronger in participants with BMI ≥ 24 kg/m2 group (ß = - 0.0159, 95% CI: - 0.0289, - 0.0029). The results of sensitivity analyses were consistent with the main results. CONCLUSION: We have identified a negative correlation between serum RC and hip BMD, and a higher RC concentration was found to be associated with a greater risk of low bone mass in young and middle-aged men.
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Densidade Óssea , Colesterol , Humanos , Masculino , Estudos Transversais , Densidade Óssea/fisiologia , Pessoa de Meia-Idade , Adulto , Colesterol/sangue , Índice de Massa Corporal , Osteoporose/epidemiologia , Osteoporose/etiologia , Osteoporose/sangue , Fatores de Risco , Biomarcadores/sangueRESUMO
BACKGROUND: Clopidogrel resistance (CR) is associated with adverse clinical outcomes in acute ischemic stroke or transient ischemic attack (TIA) patients. However, whether CR affects the long-term clinical prognosis remains to be clarified. The ABCD-GENE score is a novel risk model that identifies CR in cardiovascular disease patients; its diagnostic ability and application in ischemic stroke or TIA remain to be studied. This study aimed to investigate the diagnostic ability of the ABCD-GENE score for CR and analyze the relationship between CR and long-term clinical prognosis in patients with ischemic stroke or TIA. METHODS: From January 2018 to January 2021, 251 ischemic stroke or TIA patients who were treated with clopidogrel for more than three months after onset and maintained the medication until the follow-up time were enrolled, and platelet reactivity was detected by thromboelastography. CYP2C19 gene analysis was performed. Adverse clinical outcomes were recorded from 3months after onset. The median follow-up time was 878days. RESULTS: The prevalence of CR was 33.9%. The proportion of CYP2C19 loss-of-function carriers was 62.2%. The ABCD-GENE score≥10 was independently associated with CR (OR=1.82, 95% CI: 1.02-3.24, P=0.041), and the C-statistic value of the score (as a binary and integer variable) on CR was 0.58 and 0.63, respectively. The risk of long-term adverse clinical outcomes was not significantly different between CR and clopidogrel sensitive groups (12.94% vs. 11.44%, HR=1.22, 95% CI: 0.57-2.62, P=0.603). A similar result was observed between ABCD-GENE score≥10 and ABCD-GENE score<10 groups (10.38% vs. 12.64%, HR=1.19, 95% CI: 0.55-2.60, P=0.666). CONCLUSIONS: In ischemic stroke or TIA patients, the ABCD-GENE score could identify the risk of CR. CR was not associated with long-term adverse clinical outcomes.
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Clopidogrel , Citocromo P-450 CYP2C19 , Resistência a Medicamentos , Ataque Isquêmico Transitório , AVC Isquêmico , Inibidores da Agregação Plaquetária , Humanos , Clopidogrel/uso terapêutico , Masculino , Ataque Isquêmico Transitório/tratamento farmacológico , Ataque Isquêmico Transitório/genética , Ataque Isquêmico Transitório/epidemiologia , Ataque Isquêmico Transitório/diagnóstico , Feminino , Pessoa de Meia-Idade , Idoso , Inibidores da Agregação Plaquetária/uso terapêutico , Prognóstico , AVC Isquêmico/genética , AVC Isquêmico/epidemiologia , AVC Isquêmico/diagnóstico , AVC Isquêmico/tratamento farmacológico , Resistência a Medicamentos/genética , Citocromo P-450 CYP2C19/genética , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico , Seguimentos , Idoso de 80 Anos ou maisRESUMO
Objective: This paper provides a brief overview of the epidemiology of colorectal cancer in China and around the world, and discusses how to prevent colorectal cancer to reduce its disease burden. Method: Using the official database of GLOBOCAN 2020, the China Cancer Registry Annual Report compiled by the National Cancer Center, and data from CONCORD-3.Data management was performed by Microsoft Excel 2016 and R 4.2.1 Relevant graphs were generated using the ggplot2 package for result visualization. Result: An estimated 1 931 590 people were diagnosed with colorectal cancer worldwide in 2020 with an age-standardized incidence rate of 19.5 per 100 000. There were about 935 173 deaths caused by colorectal cancer internationally, with an age-standardized mortality rate of 9.0 per 100 000. Overall, colorectal cancer was the fourth most commonly diagnosed cancer and the third leading cause of cancer-related death worldwide in 2020. In China, the age-standardized incidence rate and mortality rate of colorectal cancer was 17.3 per 100 000 and 7.8 per 100 000, respectively. Gender differences in trends were observed, with a decreasing trend in incidence and mortality among females and an increasing trend in incidence and mortality among males. The primary risk factors for colorectal cancer include age, genetic factors, gastrointestinal disorders, dietary habits, and lifestyle et al. Conclusions: Colorectal cancer poses a significant burden globally and in China. The occurrence of colorectal cancer is closely related to physiology, genetics, behavioral habits, lifestyle, and disease factors. To better control the colorectal cancer burden with the lowest cost, specific measures should be taken to reduce exposure to established risk factors. By combining the disease prevention and control strategies of tertiary prevention in China with the characteristic factors of colorectal cancer, the incidence and mortality of colorectal cancer may be effectively controlled.
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Neoplasias Colorretais , Feminino , Masculino , Humanos , Prevalência , China/epidemiologia , Bases de Dados Factuais , Sistema de Registros , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controleRESUMO
Objective: To analyze the detection of colorectal advanced neoplasms in the population who underwent colonoscopy screening in Henan Province as part of the Urban China Cancer Screening Program and its influencing factors. Methods: A cross-sectional study design was employed. Based on the Cancer Screening Program conducted in Henan Province, the study enrolled 7 454 urban residents who manifested no symptoms and were recruited from eight cities in the province, including Zhengzhou, Zhumadian, Anyang, Luoyang, Nanyang, Jiaozuo, Xinxiang, and Puyang from October 2013 to October 2019, and participated in colonoscopy screening. The χ2 test was used to compare the detection rates of colorectal advanced neoplasms among participants with different characteristics, and a multivariate logistic stepwise regression model was used to analyze the factors affecting the detection rates. Results: A total of 7 454 subjects underwent colonoscopy screening, and 112 cases of colorectal advanced neoplasms were detected. Multivariate logistic regression analysis suggested that older age, smoking, higher meat intake, history of diabetes, and family history of colorectal cancer in a first-degree relative were risk factors for colorectal advanced neoplasms. The detection rate was significantly higher in people aged 60-74 years compared with those aged 40-49 years, with an odds ratio (OR) of 2.04 (95% CI: 1.23-3.38).The rates were higher in people who smoked than those who did not smoke, with an OR of 2.21 (95% CI: 1.48-3.31), and in people who consumed more meat than those who consumed less, with an OR of 1.53 (95% CI: 1.04-2.26). Those with diabetes had a higher detection rate compared with those without, with an OR of 1.69 (95% CI: 1.07-2.69), and those with a first-degree family history of colorectal cancer had a higher detection rate than those without, with an OR of 1.64 (95% CI: 1.09-2.46). Conclusion: The detection rate of colorectal advanced neoplasms through colonoscopy screening in Henan Province covered by the Urban China Cancer Screening Program is 1.50%. Older age, smoking, higher meat intake, history of diabetes, and family history of colorectal cancer in a first-degree relative are identified as risk factors for colorectal advanced neoplasms.
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Colonoscopia , Neoplasias Colorretais , Detecção Precoce de Câncer , População Urbana , Humanos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Pessoa de Meia-Idade , Estudos Transversais , China/epidemiologia , Detecção Precoce de Câncer/métodos , Idoso , Fatores de Risco , População Urbana/estatística & dados numéricos , Masculino , Feminino , Adulto , Programas de Rastreamento/métodos , Modelos Logísticos , Fumar/epidemiologia , Fatores EtáriosRESUMO
Objective: To deepen understanding of IgG4-related diseases (RDs), we analyzed the associated lymphocyte subtypes, and explored the pathogenesis and potential immunotherapeutic targets. Methods: Eighty-six patients with IgG4-RDs were enrolled, and their clinical characteristics, peripheral lymphocyte subtypes, and disease course were analyzed. Results: The mean age of the participants was 36-87(62±11) years; 51 were male (59.3%) and 35 were women (40.7%); and 34.9% had a history of allergy. Follow-up lasted 4.8 (0.4, 14.1) months. The most common symptoms were abdominal pain, and submandibular gland and lacrimal gland swelling (each 20.9%). Sixty-five (75.6%) participants had multiple organ involvement, and the most frequently affected organs were the pancreas (52.3%), submandibular gland (51.2%), and lacrimal gland (34.9%). A high eosinophil count; high IgE, IgG, IgG1, and IgG4 concentrations; and low complement C3 and C4 concentrations were present in 18.8% (16/85), 30.0% (24/80), 72.9% (62/85), 58.3% (28/48), 89.5% (77/86), 61.2% (52/85), and 50.0% (42/84), respectively, of the participants. In addition, 64.7% (55/85) were positive for autoantibodies, and the most frequent was anti-nuclear antibody (63.5%). The proportion of CD4+T lymphocytes increased in 25.7% (9/35) of the participants, which was accompanied by an increase in the ratio of CD4+/CD8+T lymphocytes (22.9%, 8/35). Importantly, most participants (90.0%, 18/20) had a high proportion of regulatory T (Treg) cells. High interleukin (IL)-2, IL-6, and IL-10 concentrations were present in 50.0% (11/22), 33.3% (10/30), and 16.7% (5/30), respectively, of the participants. Substantial lymphoplasmacytic infiltration, fibrosis, IgG4-positive plasma cell infiltration, and lymphoid follicle hyperplasia or ectopic formation were present in 79.2% (42/53), 67.9%(36/53), 35.8%(19/53) and 30.2% (16/53), respectively, of the participants. Fifty-three participants with detailed pathologic data were also further evaluated, of whom 24.5% (13/53), 3.8% (2/53), and 67.9% (36/53) had definite, probable, and possible diagnoses; and 3.8% (2/53) could not be diagnosed. Compared with baseline, the percentage of eosinophils and the IgE, IgG, and IgG4 concentrations decreased significantly; and the complement C3 and C4 concentrations had increased significantly after 6 months of treatment (all P<0.05). The IgG4 concentration after 6 months of treatment negatively correlated with that of C4, and positively correlated with the baseline concentration of IgE and the IgG4/IgG ratio. Conclusion: IgG4-RDs are a group of diseases characterized by male predisposition; multiple organ involvement; a high eosinophil count; high IgE, IgG, IgG1, and IgG4 concentrations; and a low C3 concentration. Peripheral CD4+T cells and Treg cells are also more abundant. The diseases can be controlled with glucocorticoids and immunosuppressive drugs in the majority of instances. The IgG4 concentration after 6 months of treatment negatively correlates with the baseline complement C4 concentration and positively correlates with the IgE concentration and IgG4/IgG ratio, which suggests that IgG4/IgG, IgE, and complement should be closely monitored to evaluate disease activity and the efficacy of treatment in such patients.
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Complemento C3 , Imunoglobulina G , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Glucocorticoides/uso terapêutico , Linfócitos , Imunoglobulina ERESUMO
The clinical data of 23 patients undergoing real-time echocardiography-guided infusion port implantation in the Breast Center of Tsinghua Changgung Hospital in Beijing from January to July 2021 were analyzed. The length of catheter insertion L1 was initially estimated using surface measurement method in all patients. Intraoperatively, transthoracic echocardiography was applied using the parasternal four-chamber view to visualize the catheter image within the right atrium, and the length of catheter insertion L2 was recorded under the guidance of echocardiography. Postoperatively, chest radiographs were taken in the upright position to observe the position of the catheter tip. According to chest CT scans, the ideal length (L) for catheter tip placement was calculated when it was located at the junction of superior vena cava and right atrium. Bland-Altman scatter plot analysis and linear regression fitting test were used on L1 and L2 respectively with L to evaluate the consistency. A total of 23 patients were included in this study, among which one case of left breast cancer patient undergoing breast-conserving surgery had difficulty in identifying the catheter tip position due to residual pleural effusion obscuring the imaging of the cardiac apex four-chamber view. In 22 patients, the results of intraoperative ultrasound imaging were good, including 1 case of catheter ectopic to azygos vein, and 21 cases of right atrial catheter could be detected by ultrasound. Statistical analysis showed that there was a good consistency between L1 and L, L2 and L, and the difference between them was d=0.28 cm (95%CI:-1.76-2.31 cm) and d=0.20 cm(95%CI:-0.84-1.23 cm), respectively, with no statistical significance (P>0.05). In the linear regression model, L2 and L had a higher fit than L1, and the difference was statistically significant (R²=0.954, P<0.001). This study found that real-time echocardiographic localization technique can be applied in adult port surgery to replace X-ray-guided real-time catheter tip detection and adjustment to the optimal position.
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Cateterismo Venoso Central , Cateteres Venosos Centrais , Adulto , Humanos , Cateteres de Demora , Ecocardiografia/métodos , Veia Cava Superior/diagnóstico por imagem , FemininoRESUMO
Objective: To investigate the impact of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease (COPD). Methods: A retrospective cohort study was performed to include 178 patients with â ¢-â £ NSCLC complicated with COPD who received at least 2 times of immunotherapy in Xinqiao Hospital of the Army Medical University from January 2019 to August 2021. Baseline peripheral blood inflammatory indicators such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) were collected within 2 weeks before the first treatment, with the last one being on or before February 7, 2022. X-tile software was used to determine the optimal cut-off value of peripheral blood inflammatory indicators. The Cox multivariate regression models were used to analyze the factors affecting progression free survival (PFS) and overall survival (OS). Results: Among the 178 patients, there were 174 males (97.8%) and 4 females (2.2%); the age ranged from 42 to 86 (64.3±8.3) years old.There were 30 cases (16.9%) of immunotherapy monotherapy, 114 cases (64.0%) of immunotherapy combined with chemotherapy, 21 cases (11.8%) of immunotherapy combined with antivascular therapy, and 13 cases (7.3%) of immunotherapy combined with radiotherapy. The median follow-up period was 14.5 months (95%CI: 13.6-15.3 months). The objective response rate (ORR) and disease control rate (DCR) were 44.9% (80/178) and 90.4% (161/178) for the whole group, the median PFS was 14.6 months (95%CI: 11.6-17.6 months), and the median OS was 25.7 months (95%CI: 18.0-33.4 months). The results of Cox multivariate analysis showed that IL-6>9.9 ng/L (HR=5.885, 95%CI: 2.558-13.543, P<0.01), TNF-α>8.8 ng/L (HR=3.213, 95%CI: 1.468-7.032, P=0.003), IL-8>202 ng/L (HR=2.614, 95%CI: 1.054-6.482, P=0.038), systemic immune inflammatory index (SII)>2 003.95 (HR=2.976, 95%CI: 1.647-5.379, P<0.001) were risk factors for PFS, and advanced lung cancer inflammation index (ALI)>171.15 was protective factor for PFS (HR=0.545, 95%CI: 0.344-0.863, P=0.010). IL-6>9.9 ng/L(HR=6.124, 95%CI: 1.950-19.228, P<0.002), lactate dehydrogenase (LDH)>190.7 U/L (HR=2.776, 95%CI: 1.020-7.556, P=0.046), SII>2 003.95 (HR=4.521, 95%CI: 2.241-9.120, P<0.001) were risk factors for OS, and ALI>171.15 was a protective factor for OS (HR=0.434, 95%CI: 0.243-0.778, P=0.005). Conclusion: Baseline high levels of IL-6, TNF-α, IL-8, SII, LDH, and low levels of ALI are risk factors for poor prognosis in patients with advanced NSCLC-COPD receiving immunotherapy.
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Carcinoma Pulmonar de Células não Pequenas , Imunoterapia , Interleucina-6 , Neoplasias Pulmonares , Doença Pulmonar Obstrutiva Crônica , Fator de Necrose Tumoral alfa , Humanos , Masculino , Feminino , Carcinoma Pulmonar de Células não Pequenas/terapia , Doença Pulmonar Obstrutiva Crônica/terapia , Doença Pulmonar Obstrutiva Crônica/sangue , Pessoa de Meia-Idade , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/sangue , Idoso , Estudos Retrospectivos , Interleucina-6/sangue , Adulto , Fator de Necrose Tumoral alfa/sangue , Inflamação , Interleucina-8/sangue , Idoso de 80 Anos ou maisRESUMO
Objective: To investigate the clinical, radiological, and pathological features of anaplastic gangliogliomas (AGGs) and to determine whether these tumors represent a distinct entity. Methods: Consecutive 667 cases of ganglioglioma (GG) diagnosed at the Xuanwu Hospital, Capital Medical University, Beijing, China between January 2015 and July 2023 were screened. Among these cases, 9 pathologically confirmed AGG cases were identified. Their clinical, radiological, treatment, and outcome data were analyzed retrospectively. Most of the tumor samples were subject to next-generation sequencing, while a subset of them were subject to DNA methylation profiling. Results: Among the 9 patients, there were five males and four females, with a median age of 8 years. Epileptic seizures (5/9) were the most frequently presented symptom. Radiological examinations showed three types of radiological manifestations: four cases showed abnormal MRI signals with no significant mass effects and mild enhancement; two cases demonstrated a mixed solid-cystic density lesion with peritumoral edema, which showed significant heterogeneous enhancement and obvious mass effects, and one case displayed cystic cavity formation with nodules on MRI, which showed evident enhancements. All cases exhibited mutations that were predicted to activate the MAP kinase signaling pathway, including seven with BRAF p.V600E mutation and two with NF1 mutation. Five AGGs with mutations involving the MAP kinase signaling pathway also had concurrent mutations, including three with CDKN2A homozygous deletion, one with a TERT promoter mutation, one with a H3F3A mutation, and one with a PTEN mutation. Conclusions: AGG exhibits a distinct spectrum of pathology, genetic mutations and clinical behaviors, differing from GG. Given these characteristics suggest that AGG may be a distinct tumor type, further expansion of the case series is needed. Therefore, a comprehensive integration of clinical, histological, and molecular analyses is required to correctly diagnose AGG. It will also help guide treatments and prognostication.
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Neoplasias Encefálicas , Metilação de DNA , Ganglioglioma , Imageamento por Ressonância Magnética , Mutação , PTEN Fosfo-Hidrolase , Proteínas Proto-Oncogênicas B-raf , Humanos , Ganglioglioma/patologia , Ganglioglioma/genética , Masculino , Feminino , Criança , Estudos Retrospectivos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Proteínas Proto-Oncogênicas B-raf/genética , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Telomerase/genética , Histonas/genética , Histonas/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Epilepsia/patologia , Epilepsia/genéticaRESUMO
Objective: To analyze the clinical data of a case of lung adenocarcinoma with Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) resistance transforming into sarcoma, and to conduct a literature review to improve the understanding of the resistance mechanism. Histological transformation is a unique form of acquired resistance of EGFR-TKIs in non-small cell lung cancer (NSCLC). Thereinto, the transformation of small cell carcinoma is more common, and the transformation of sarcoma is rarely reported. Methods: Clinicopathological data on the treatment process, pathological features, and clinical outcome of the patient with EGFR-TKIs-resistance lung adenocarcinoma transforming into sarcoma were collected. The literature was reviewed to analyze the pathogenetic mechanism for sarcomatoid carcinoma or sarcoma transformation after drug resistance of adenocarcinoma, as well as the clinical characteristics of the patients and the corresponding therapeutic schemes. Results: We reported a patient with lung adenocarcinoma who developed EGFR-T790M mutation after first-line treatment with icotinib and sarcoma transformation after second-line treatment with almonertinib. Chemotherapy, radioactive particle implantation, antiangiogenic therapy and immunotherapy were followed, but the results were unsatisfactory. There was no report of EGFR-TKIs-resistant lung adenocarcinoma transforming into sarcoma. Among the 14 reports of adenocarcinoma transforming into sarcomatoid carcinoma, 8 cases had EGFR mutation, 3 cases had ALK mutation, 2 cases had ROS1 mutation, and 1 case had no asscoiated sensitive mutation. The median survival of 14 patients with adenocarcinoma transforming to sarcomatoid carcinoma was only 3 months. Conclusions: Sarcoma transformation can be one of the forms of drug resistance in patients with lung adenocarcinoma with EGFR-TKIs. The prognosis of patients with adenocarcinoma after transformation into sarcoma is poor.
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Adenocarcinoma de Pulmão , Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Sarcoma , Humanos , Adenocarcinoma/genética , Adenocarcinoma de Pulmão/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/genética , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Sarcoma/genética , Sarcoma/tratamento farmacológicoRESUMO
A 21-year-old female patient presented to the Ophthalmology Department of Yunnan University Affiliated Hospital with complaints of "bilateral blurred vision accompanied by diplopia for 3 weeks". The patient's main symptoms included intermittent visual blurring, diplopia, headaches, and ocular discomfort. Ocular examination revealed intermittent exotropia, sometimes accompanied by esotropia or orthotropia, along with signs of pupillary constriction and pseudomyopia. Based on the clinical presentation, a diagnosis of intermittent exotropia complicated by spasm of the near reflex (SNR) was made. The patient underwent bilateral exotropia surgery, which corrected the ocular alignment and resolved the symptoms and signs of SNR postoperatively.
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Exotropia , Humanos , Feminino , Adulto Jovem , Espasmo/complicações , Diplopia/etiologiaRESUMO
We present a new determination of the smallest neutrino mixing angle θ_{13} and the mass-squared difference Δm_{32}^{2} using a final sample of 5.55×10^{6} inverse beta-decay (IBD) candidates with the final-state neutron captured on gadolinium. This sample is selected from the complete dataset obtained by the Daya Bay reactor neutrino experiment in 3158 days of operation. Compared to the previous Daya Bay results, selection of IBD candidates has been optimized, energy calibration refined, and treatment of backgrounds further improved. The resulting oscillation parameters are sin^{2}2θ_{13}=0.0851±0.0024, Δm_{32}^{2}=(2.466±0.060)×10^{-3} eV^{2} for the normal mass ordering or Δm_{32}^{2}=-(2.571±0.060)×10^{-3} eV^{2} for the inverted mass ordering.
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Reactor neutrino experiments play a crucial role in advancing our knowledge of neutrinos. In this Letter, the evolution of the flux and spectrum as a function of the reactor isotopic content is reported in terms of the inverse-beta-decay yield at Daya Bay with 1958 days of data and improved systematic uncertainties. These measurements are compared with two signature model predictions: the Huber-Mueller model based on the conversion method and the SM2018 model based on the summation method. The measured average flux and spectrum, as well as the flux evolution with the ^{239}Pu isotopic fraction, are inconsistent with the predictions of the Huber-Mueller model. In contrast, the SM2018 model is shown to agree with the average flux and its evolution but fails to describe the energy spectrum. Altering the predicted inverse-beta-decay spectrum from ^{239}Pu fission does not improve the agreement with the measurement for either model. The models can be brought into better agreement with the measurements if either the predicted spectrum due to ^{235}U fission is changed or the predicted ^{235}U, ^{238}U, ^{239}Pu, and ^{241}Pu spectra are changed in equal measure.
Assuntos
Reatores Nucleares , UrânioRESUMO
PURPOSE: To compare fixed transverse textile electrodes (TTE) knitted into a sock versus motor point placed standard gel electrodes (MPE) on peak venous velocity (PVV) and discomfort, during calf neuromuscular electrical stimulation (calf-NMES). METHODS: Ten healthy participants received calf-NMES with increasing intensity until plantar flexion (measurement level I = ML I), and an additional mean 4 mA intensity (ML II), utilizing TTE and MPE. PVV was measured with Doppler ultrasound in the popliteal and femoral veins at baseline, ML I and II. Discomfort was assessed with a numerical rating scale (NRS, 0-10). Significance was set to p < 0.05. RESULTS: TTE and MPE both induced significant increases in PVV from baseline to ML I and significantly higher increases to ML II, in both the popliteal and femoral veins (all p < 0.001). The popliteal increases of PVV from baseline to both ML I and II were significantly higher with TTE versus MPE (p < 0.05). The femoral increases of PVV from baseline to both ML I and II were not significantly different between TTE and MPE. TTE versus MPE resulted at ML I in higher mA and NRS (p < 0.001), and at ML II in higher mA (p = 0.005) while NRS was not significantly different. CONCLUSION: TTE integrated in a sock produces intensity-dependent increases of popliteal and femoral hemodynamics comparable to MPE, but results in more discomfort at plantar flexion due to higher current required. TTE exhibits in the popliteal vein higher increases of PVV compared to MPE. TRIAL REGISTRATION: Trial_ID: ISRCTN49260430. Date: 11/01/2022. Retrospectively registered.
Assuntos
Hemodinâmica , Perna (Membro) , Humanos , Estimulação Elétrica/efeitos adversos , Hemodinâmica/fisiologia , Perna (Membro)/irrigação sanguínea , Veia Poplítea/diagnóstico por imagem , Veia Poplítea/fisiologia , UltrassonografiaRESUMO
PURPOSE: Physical inactivity is associated with muscle atrophy and venous thromboembolism, which may be prevented by neuromuscular electrical stimulation (NMES). This study aimed to investigate the effect on discomfort, current amplitude and energy consumption when varying the frequency and phase duration of low-intensity NMES (LI-NMES) via a sock with knitting-integrated transverse textile electrodes (TTE). METHODS: On eleven healthy participants (four females), calf-NMES via a TTE sock was applied with increasing intensity (mA) until ankle-plantar flexion at which point outcomes were compared when testing frequencies 1, 3, 10 and 36 Hz and phase durations 75, 150, 200, 300 and 400 µs. Discomfort was assessed with a numerical rating scale (NRS, 0-10) and energy consumption was calculated and expressed in milli-Joule (mJ). Significance set to p ≤ 0.05. RESULTS: 1 Hz yielded a median (inter-quartile range) NRS of 2.4 (1.0-3.4), significantly lower than both 3 Hz with NRS 2.8 (1.8-4.2), and 10 Hz with NRS 3.4 (1.4-5.4) (both p ≤ .014). Each increase in tested frequency resulted in significantly higher energy consumption, e.g. 0.6 mJ (0.5-0.8) for 1 Hz vs 14.9 mJ (12.3-21.2) for 36 Hz (p = .003). Longer phase durations had no significant effect on discomfort despite generally requiring significantly lower current amplitudes. Phase durations 150, 200 and 400 µs required significantly lower energy consumption compared to 75 µs (all p ≤ .037). CONCLUSION: LI-NMES applied via a TTE sock produces a relevant plantar flexion of the ankle with the best comfort and lowest energy consumption using 1 Hz and phase durations 150, 200 or 400 µs.
Assuntos
Terapia por Estimulação Elétrica , Músculo Esquelético , Feminino , Humanos , Músculo Esquelético/fisiologia , Perna (Membro) , Terapia por Estimulação Elétrica/métodos , Estimulação Elétrica/métodos , VestuárioRESUMO
Objective: Patients with advanced sarcomas have a dismal prognosis with few effective therapies. The purpose of this study was to evaluate the efficacy and safety of anlotinib in the treatment of advanced sarcoma and to explore the relationship between adverse events (AEs) and efficacy. Methods: Data from 45 advanced sarcoma patients who received anlotinib monotherapy at Affiliated Cancer Hospital of Zhengzhou University between June 2018 and August 2021 were retrospectively analyzed. According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1, the objective remission rate (ORR) and disease control rate (DCR) were calculated, and the progression free survival (PFS) and treatment-related AEs were recorded and analyzed. Survival analysis was conducted using the Kaplan-Meier survival rates were compared using the Log rank test. Results: Forty patients were treated for more than 1.5 months and received efficacy evaluation. The ORR and DCR after 3 months were 7.5%(3/40) and 80.0%(32/40), respectively. The overall ORR was 2.5%(1/40), the total DCR was 27.5%(11/40), and the median progression-free survival (m-PFS) was 6.70 months; The m-PFS of alveolar soft tissue sarcoma (ASPS) was 10.27 months, which was significantly longer than that of other subtypes of sarcoma (P=0.048). In addition, the DCR of ASPS and synovial sarcoma (SS) was significantly better than that of osteosarcoma (P<0.05). The most common AEs were elevated thyroid stimulating hormone (17.8%, 8/45), anemia (15.6%, 7/45), fatigue (11.1%, 5/45). Five patients developed grade 3 AEs after treatment; The PFS of patients with hand-foot syndrome after treatment was significantly longer than that of patients without hand-foot syndrome (14.10 vs 6.00, P=0.024). Conclusions: The efficacy of anlotinib in the treatment of ASPS and SS is better than that of other subtypes. The PFS in the group with hand-foot syndrome was significantly longer than that of the group without hand-foot syndrome.