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AIM: Ki-67 is a marker of cell proliferation and is increasingly being used as a primary outcome measure in preoperative window studies of endometrial cancer (EC). This study explored the feasibility of using apparent diffusion coefficient (ADC) values in noninvasive prediction of Ki-67 expression levels in EC patients before surgery, and constructs a nomogram by combining clinical data. MATERIAL AND METHODS: This study retrospectively analyzed 280 EC patients who underwent preoperative magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) in our hospital from January 2017 to February 2023. Evaluate the potential nonlinear relationship between ADC values and Ki-67 expression using the nomogram. The included patients were randomized into a training set (n = 186) and a validation set (n = 84). Using a combination of logistic regression and LASSO regression results, from which the four best predictors were identified for the construction of the nomogram. The accuracy and clinical applicability of the nomogram were assessed using the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). RESULTS: The results of this study showed a nonlinear correlation between ADCmin and Ki-67 expression (nonlinear P = 0.019), and the nonlinear correlation between ADCmean and Ki-67 expression (nonlinear P = 0.019). In addition, this study constructed the nomogram by incorporating ADCmax, International Federation of Gynecology and Obstetrics (FIGO), and chemotherapy. The area under the curve (AUC) values of the ROC for nomogram, ADCmax, FIGO, chemotherapy and grade in the training set were 0.783, 0.718, 0.579, 0.636, and 0.654, respectively. In the validation set, the AUC values for nomogram, ADCmax, FIGO, chemotherapy, and grade were 0.820, 0.746, 0.558, 0.542, and 0.738, respectively. In addition, the calibration curves and the DCA curves suggested a better predictive efficacy of the model. CONCLUSION: A nomogram prediction model constructed on the basis of ADCmax values combined with clinical data can be used as an effective method to noninvasively assess Ki-67 expression in EC patients before surgery.
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We report the first double-differential neutrino-argon cross section measurement made simultaneously for final states with and without protons for the inclusive muon neutrino charged-current interaction channel. The proton kinematics of this channel are further explored with a differential cross section measurement as a function of the leading proton's kinetic energy that extends across the detection threshold. These measurements use data collected with the MicroBooNE detector from 6.4×10^{20} protons on target from the Fermilab booster neutrino beam with a mean neutrino energy of â¼0.8 GeV. Extensive data-driven model validation utilizing the conditional constraint formalism is employed. This motivates enlarging the uncertainties with an empirical reweighting approach to minimize the possibility of extracting biased cross section results. The extracted nominal flux-averaged cross sections are compared to widely used event generator predictions revealing severe mismodeling of final states without protons for muon neutrino charged-current interactions, possibly from insufficient treatment of final state interactions. These measurements provide a wealth of new information useful for improving event generators which will enhance the sensitivity of precision measurements in neutrino experiments.
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Objective: To evaluate the effect of the implementation of Beijing Smoking Control Regulation in 2015 on the smoking prevalence in people aged ≥15 years in Beijing during 2014-2021, and explore factors associated with tobacco use behavior in local population. Methods Using a pooled cross-sectional design, data from Beijing Adult Tobacco Survey in 2014, 2016, 2019 and 2021 (4 surveys) were combined into one dataset. The 4 surveys used same multistage cluster sampling procedure. After complex survey weighting, multiple logistic regression models were constructed to analyze factors influencing smoking status. Results: A total of 8 484, 9 372, 8 534 and 10 551 respondents were included in the surveys in 2014, 2016, 2019 and 2021, respectively. The smoking prevalence rate was 23.4%, 22.3%, 20.3% and 19.9%, respectively, in Beijing residents aged ≥15 years, exhibiting a linear declining trend (P=0.010). Factors associated with current smoking in men were age 25-44 years (OR=2.22, 95%CI: 1.68-2.95) and 45-64 years, (OR=2.64, 95%CI: 2.06-3.39), educational level of high school (OR=0.69, 95%CI: 0.49-0.95) and undergraduate and above (OR=0.46, 95%CI: 0.33-0.63), and awareness of smoking causing stroke (OR=0.71, 95%CI: 0.61-0.81), and awareness of smoking causing lung cancer (OR=0.53, 95%CI: 0.42-0.66), the differences were significant (all P<0.05). After controlling interfering factors, the current smoking prevalence in men in 2019 (OR=0.73, 95%CI: 0.63-0.87, P<0.001) and 2021 (OR=0.72, 95%CI: 0.61-0.88, P<0.001) were significantly lower than that in 2014. Factors associated with current smoking in women were living alone (OR=1.80, 95%CI: 1.33-2.44), educational level of undergraduate and above (OR=0.43, 95%CI: 0.27-0.69), other occupations except doctor and teacher (OR=8.54, 95%CI: 2.80-26.02) or being retired/unemployed (OR=9.39, 95%CI: 3.19-27.65), and awareness of smoking causing cardiovascular events (OR=0.58, 95%CI: 0.39-0.84), and awareness of smoking causing lung cancer (OR=0.54, 95%CI: 0.35-0.83), the differences were significant (all P<0.05). No significant change in smoking status in women was found in 4 surveys. Conclusions: The smoking prevalence rate in men in Beijing has declined since the implementation of Beijing Smoking Control Regulation 5 years, indicating the effectiveness of legislative approach in tobacco control. Socio-demographic factors and the awareness level of tobacco harm could influence smoking status. Future tobacco control programs should target the people with lower education level, young men, women living alone, and those with occupations other than teachers/doctors or the unemployed/retired and include more comprehensive health education.
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Fumar Tabaco , Humanos , Beijing/epidemiología , Estudios Transversales , Adulto , Fumar Tabaco/epidemiología , Prevalencia , Masculino , Adolescente , Persona de Mediana Edad , Femenino , Adulto Joven , Fumar/epidemiología , Anciano , Modelos LogísticosRESUMEN
Denosumab, a human monoclonal antibody, is used for the prevention of malignant tumor-related bone events and the treatment of osteoporosis with high fracture risk. Since its approval in China in 2019, denosumab-related osteonecrosis of the jaw (DRONJ) has attracted increasing attention. DRONJ, similar to bisphosphonate-related osteonecrosis of the jaw, often occurs after tooth extraction and manifests as exposed bone necrosis, purulent discharge, facial swelling and pain, severely impacting patients' quality of life. However, the perioperative management strategies for DRONJ differ from those for bisphosphonate-related osteonecrosis of the jaw. This article summarizes the perioperative management strategies for high-risk DRONJ patients from aspects such as oral hygiene care, antibiotic use, drug discontinuation during the perioperative period, and surgical strategy selection, aiming to provide guidance for oral surgeons in managing tooth extraction in denosumab-treated patients.
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Objective: To retrospectively analyze the clinical and pathologic characteristics, response to treatment, survival, and prognosis of patients with primary large B-cell lymphoma of the central nervous system (PCNSLBCL) . Methods: Clinical and pathologic data of 70 patients with PCNSLBCL admitted to Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2010 to November 2022 were collected for retrospective analysis. Survival analysis was performed using the Kaplan-Meier method and log-rank test, and prognosis analysis was conducted using the Cox proportional hazards model. Results: Among 70 patients with PCNSLBCL, complete remission (CRs) were achieved in 49 (70.0% ) and partial remission in 4 (5.7% ) after the first-line induction therapy; the overall remission rate was 75.7%. The 2-year progression-free survival (PFS) rate was 55.8% and the median progression-free survival (mPFS) time was 35.9 months, whereas the 2-year overall survival (OS) rate was 79.1% with a median OS time not reached. After CR induced by first-line therapy, cumulative incidence of relapse (CIR) was lower in patients who had received auto-HSCT than in those who had not received consolidation therapy (P=0.032), whose 2-year PFS rate was 54.4% and mPFS time was 35.9 months; comparatively, the 2-year PFS rate in patients having received oral maintenance of small molecule drugs reached 84.4% with a mPFS time of 79.5 months (P=0.038). Multivariant analysis demonstrated that Class 3 in the Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic model is an independent adverse prognostic factor of OS in patients with PCNSLBCL (HR=3.127, 95% CI 1.057-9.253, P=0.039) . Conclusions: In patients with PCNSLBCL achieving CR after the first-line induction therapy, auto-HSCT as consolidation therapy would lead to a decreased CIR, and PFS time could be prolonged by oral maintenance of small molecule drugs. Class 3 MSKCC prognostic model is independently associated with poorer OS.
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Neoplasias del Sistema Nervioso Central , Humanos , Estudios Retrospectivos , Neoplasias del Sistema Nervioso Central/terapia , Neoplasias del Sistema Nervioso Central/patología , Pronóstico , Tasa de Supervivencia , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/mortalidad , Inducción de Remisión , Análisis de Supervivencia , Modelos de Riesgos Proporcionales , Masculino , Femenino , Persona de Mediana EdadRESUMEN
We present a first search for dark-trident scattering in a neutrino beam using a dataset corresponding to 7.2×10^{20} protons on target taken with the MicroBooNE detector at Fermilab. Proton interactions in the neutrino target at the main injector produce π^{0} and η mesons, which could decay into dark-matter (DM) particles mediated via a dark photon A^{'}. A convolutional neural network is trained to identify interactions of the DM particles in the liquid-argon time projection chamber (LArTPC) exploiting its imagelike reconstruction capability. In the absence of a DM signal, we provide limits at the 90% confidence level on the squared kinematic mixing parameter ϵ^{2} as a function of the dark-photon mass in the range 10≤M_{A^{'}}≤400 MeV. The limits cover previously unconstrained parameter space for the production of fermion or scalar DM particles χ for two benchmark models with mass ratios M_{χ}/M_{A^{'}}=0.6 and 2 and for dark fine-structure constants 0.1≤α_{D}≤1.
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A ligature-induced periodontitis model was established in wild-type and CD146CreERT2; RosatdTomato mice to explore the function of pericytes in alveolar bone formation. We found that during periodontitis progression and periodontal wound healing, CD146+/NG2+ pericytes were enriched in the periodontal tissue areas, which could migrate to the alveolar bone surface and colocalize with ALP+/OCN+ osteoblasts. Chemokine C-X-C motif receptor 4 (CXCR4) inhibition using AMD3100 blocked CD146-Cre+ pericyte migration and osteogenesis, as well as further exacerbated periodontitis-associated bone loss. Next, primary pericytes were sorted out by magnetic-activated cell sorting and demonstrated that C-X-C motif chemokine ligand 12 (CXCL12) promotes pericyte migration and osteogenesis via CXCL12-CXCR4-Rac1 signaling. Finally, the local administration of an adeno-associated virus for Rac1 overexpression in NG2+ pericytes promotes osteoblast differentiation of pericytes and increases alveolar bone volume in periodontitis. Thus, our results provided the evidence that pericytes may migrate and osteogenesis via the CXCL12-CXCR4-Rac1 axis during the pathological process of periodontitis.
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Movimiento Celular , Quimiocina CXCL12 , Osteogénesis , Pericitos , Periodontitis , Receptores CXCR4 , Animales , Osteogénesis/fisiología , Movimiento Celular/fisiología , Ratones , Quimiocina CXCL12/metabolismo , Receptores CXCR4/metabolismo , Pérdida de Hueso Alveolar , Transducción de Señal/fisiología , Proteína de Unión al GTP rac1/metabolismo , Modelos Animales de Enfermedad , Antígeno CD146 , Osteoblastos , Diferenciación Celular , Ciclamas , BencilaminasRESUMEN
Adding synthetic nucleotides to DNA increases the linear information density of DNA molecules. Here we report that it also can increase the diversity of their three-dimensional folds. Specifically, an additional nucleotide (dZ, with a 5-nitro-6-aminopyridone nucleobase), placed at twelve sites in a 23-nucleotides-long DNA strand, creates a fairly stable unimolecular structure (that is, the folded Z-motif, or fZ-motif) that melts at 66.5 °C at pH 8.5. Spectroscopic, gel and two-dimensional NMR analyses show that the folded Z-motif is held together by six reverse skinny dZ-:dZ base pairs, analogous to the crystal structure of the free heterocycle. Fluorescence tagging shows that the dZ-:dZ pairs join parallel strands in a four-stranded compact down-up-down-up fold. These have two possible structures: one with intercalated dZ-:dZ base pairs, the second without intercalation. The intercalated structure would resemble the i-motif formed by dC:dC+-reversed pairing at pH ≤ 6.5. This fZ-motif may therefore help DNA form compact structures needed for binding and catalysis.
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Attosecond electron bunches have wide application prospects in free-electron laser injection, attosecond X/γ-ray generation, ultrafast physics, etc. Nowadays, there is one notable challenge in the generation of high-quality attosecond electron bunch, i.e., how to enhance the electron bunch density. Using theoretical analysis and three-dimensional particle-in-cell simulations, we discovered that a relativistic vortex laser pulse interacting with near-critical density plasma can not only effectively concentrate the attosecond electron bunches to over critical density, but also control the duration and density of the electron bunches by tuning the intensity and carrier-envelope phase of the drive laser. It is demonstrated that this method can efficiently produce attosecond electron bunches with a density up to 300 times of the original plasma density, peak divergence angle of less than 0.5 ∘, and duration of less than 67 attoseconds. Furthermore, by using near-critical density plasma instead of solid targets, our scheme is potential for the generation of high-repetition-frequency attosecond electron bunches, thus reducing the requirements for experiments, such as the beam alignment or target supporter.
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BACKGROUND: Clinical trial satisfaction is increasingly important for future trial designs and is associated with treatment adherence and willingness to enroll in future research studies or to recommend trial participation. In this post-trial survey, we examined participant satisfaction and attitudes toward future clinical trials in the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU). METHODS: We developed an anonymous, participant satisfaction survey tailored to participants enrolled in the DIAN-TU-001 double-blind clinical trial of solanezumab or gantenerumab and requested that all study sites share the survey with their trial participants. A total of 194 participants enrolled in the trial at 24 study sites. We utilized regression analysis to explore the link between participants' clinical trial experiences, their satisfaction, and their willingness to participate in upcoming trials. RESULTS: Survey responses were received over a sixteen-month window during 2020-2021 from 58 participants representing 15 study sites. Notably, 96.5% of the survey respondents expressed high levels of satisfaction with the trial, 91.4% would recommend trial participation, and 96.5% were willing to enroll again. Age, gender, and education did not influence satisfaction levels. Participants reported enhanced medical care (70.7%) and pride in contributing to the DIAN-TU trial (84.5%). Satisfaction with personnel and procedures was high (98.3%). Respondents had a mean age of 48.7 years, with most being from North America and Western Europe, matching the trial's demographic distribution. Participants' decisions to learn their genetic status increased during the trial, and most participants endorsed considering future trial participation regardless of the DIAN-TU-001 trial outcome. CONCLUSION: Results suggest that DIAN-TU-001 participants who responded to the survey exhibited high motivation to participate in research, overall satisfaction with the clinical trial, and willingness to participate in research in the future, despite a long trial duration of 4-7 years with detailed annual clinical, cognitive, PET, MRI, and lumbar puncture assessments. Implementation of features that alleviate barriers and challenges to trial participation is like to have a high impact on trial satisfaction and reduce participant burden.
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Enfermedad de Alzheimer , Anticuerpos Monoclonales Humanizados , Satisfacción del Paciente , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/psicología , Masculino , Femenino , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Método Doble Ciego , Adulto , Encuestas y Cuestionarios , Ensayos Clínicos como AsuntoRESUMEN
Objective: To investigate the effect of rare ginsenosides (RGS) on reproductive injury induced by cyclophosphamide (CP) in female rats. Methods: Twenty-four female rats were divided into four groups [normal control (NC), RGS, CP, and CP+RGS group] with 6 rats in each group. CP group (the model group) and CP+RGS group (the treatment group) were intraperitoneally injected with CP 30 mg/kg for 5 days for modeling, and CP+RGS group was given RGS intragastric intervention. General growth status of rats in each group was observed, the organ index was calculated, and the pathological changes of ovary, uterus, liver and kidney were observed by hematoxylin-eosin staining. Serum levels of estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), pro-inflammatory factors interleukin (IL) 6, IL-1ß, tumor necrosis factor-α were detected. The urine samples were collected after RGS treatment for metabonomics analysis. Metabolomic profiling based on ultra performance liquid chromatography (UPLC) coupled with mass spectrometry (MS) was used to analyze and determine the urine metabolites of rats in each group. Results: Compared with NC group, the ovary index of CP group [(0.054±0.015) %] was significantly decreased (P<0.05), the uterus index [(0.293±0.036) %] and estradiol level [(62.9±6.4) pmol/L] were significantly decreased (all P<0.01), serum levels of FSH, LH, IL-6 and IL-1ß [(20.4±1.0) U/L, (29.0±3.0) U/L, (185.4±28.6) ng/L, (72.9±2.0) ng/L, respectively] were significantly increased (all P<0.01). Compared with CP group, the ovary index in CP+RGS group [(0.075±0.010) %] was significantly increased (P<0.05), serum estradiol level [(122.1±16.2) pmol/L] was significantly increased (P<0.01), serum FSH, IL-1ß and IL-6 levels [(16.7±1.0) U/L, (111.8±17.4) ng/L, (60.1±2.2) ng/L, respectively] were significantly decreased (all P<0.01). Metabonomics analysis results showed that, a total of 352 metabolites were detected in urine, of which 12 were found to be potential markers associated with reproductive injury according to the screening standard. After treatment with RGS, differential metabolites were improved in the direction of NC group. Pathway enrichment suggests that the therapeutic effect of RGS was related to multiple metabolic pathways, including purine metabolism and taurine and hypotaurine metabolism. Conclusion: RGS might reduce inflammation and thus ameliorate the damage caused by CP to the reproductive system of female rats by affecting purine metabolism and other pathways.
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Ciclofosfamida , Estradiol , Hormona Folículo Estimulante , Ginsenósidos , Metabolómica , Ovario , Ratas Sprague-Dawley , Útero , Animales , Femenino , Ratas , Ciclofosfamida/efectos adversos , Ciclofosfamida/toxicidad , Ginsenósidos/farmacología , Hormona Folículo Estimulante/sangre , Estradiol/sangre , Ovario/efectos de los fármacos , Ovario/patología , Ovario/metabolismo , Útero/efectos de los fármacos , Útero/patología , Útero/metabolismo , Hormona Luteinizante/sangre , Cromatografía Líquida de Alta Presión , Interleucina-6/metabolismo , Interleucina-6/sangre , Modelos Animales de Enfermedad , Interleucina-1beta/metabolismo , Interleucina-1beta/sangre , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Espectrometría de Masas , Riñón/efectos de los fármacos , Riñón/patología , Riñón/metabolismoRESUMEN
Objective: To investigate the prognostic value of skeletal muscle measured by CT at the level of the fourth thoracic vertebra (T4) in advanced epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) patients treated with ecotinib. Methods: The study retrospectively reviewed clinical and pathological characteristics of 176 patients with advanced EGFR-positive NSCLC who received ecotinib and underwent chest CT scans at Wuhan Union Hospital between January 2017 and October 2020. Among them, 70 were male and 106 were female, with ages ranging from 27 to 80 (58.6±10.6) years. As of August 21, 2021, the median follow-up duration was 19.2 months (95%CI: 15.3 to 23.7 months). The optimal cut-off value of skeletal muscle density (T4-SMD) on CT images at the T4 level were determined using X-tile software. Kaplan-Meier analysis and log-rank test were used to plot progression-free survival curves. Cox proportional hazards regression models were employed to analyze factors influencing 1-year progression-free survival (PFS), and a nomogram prognostic model was constructed accordingly. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were utilized to evaluate the predictive value of the nomogram. Results: The T4-SMD [M (Q1,Q3)] of 176 patients was 42.56 (37.05, 45.93) HU. Patients were divided into low T4-SMD group (n=122) and high T4-SMD group (n=54) based on the cut-off value (The values for males and females were 49.44 and 41.41 HU, respectively) of T4-SMD. The median PFS time and 1-year PFS rate in the low T4-SMD group were significantly lower than those in the high T4-SMD group [10.4 (95%CI: 9.3-11.8) vs 13.7 (95%CI: 11.1-18.5) months, 36.1% vs 59.3%, respectively, P=0.034]. Eastern Cooperative Oncology Group performance status (HR=3.308, 95%CI: 1.183-9.247, P=0.023), lactate dehydrogenase level (HR=1.852, 95%CI: 1.037-3.307, P=0.037), systemic immune-inflammation index (HR=1.772, 95%CI: 1.019-3.080, P=0.043), and T4-SMD (HR=0.563, 95%CI: 0.325-0.974, P=0.040) were prognostic factors for 1-year PFS in advanced EGFR-positive NSCLC patients treated with ecotinib. A nomogram for predicting 1-year PFS of advanced EGFR-positive NSCLC patients treated with ecotinib was constructed based on the four indicators selected by multivariate Cox regression analysis. The area under the ROC curve of the nomogram was 0.775 (95%CI: 0.676-0.874). The calibration curve showed good consistency between the predicted and actual 1-year PFS. DCA demonstrated good clinical prediction effectiveness of the nomogram. Conclusion: Low T4-SMD is a prognostic risk factor for patients with advanced EGFR-positive NSCLC receiving icotinib therapy.
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Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Neoplasias Pulmonares , Músculo Esquelético , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Éteres Corona/uso terapéutico , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/tratamiento farmacológico , Músculo Esquelético/diagnóstico por imagen , Pronóstico , Quinazolinas/uso terapéutico , Estudios RetrospectivosRESUMEN
We report the picosecond spin current generation from the interface between a heavy metal and a vicinal antiferromagnet insulator Cr_{2}O_{3} by laser pulses at room temperature and zero magnetic field. It is converted into a detectable terahertz emission in the heavy metal via the inverse spin Hall effect. The vicinal interfaces are apparently the source of the picosecond spin current, as evidenced by the proportional terahertz signals to the vicinal angle. We attribute the origin of the spin current to the transient magnetic moment generated by an interfacial nonlinear magnetic-dipole difference-frequency generation. We propose a model based on the in-plane inversion symmetry breaking to quantitatively explain the terahertz intensity with respect to the angles of the laser polarization and the film azimuth. Our work opens new opportunities in antiferromagnetic and ultrafast spintronics by considering symmetry breaking.
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In this study, we examined the changes in the fibrinolytic system in a rabbit model of two acute pulmonary thromboembolisms (PTE). Fourteen healthy adult New Zealand white rabbits were divided into three groups: the single PTE group (five rabbits), the double PTE group (five rabbits), and the control group (four rabbits). A rabbit model of acute pulmonary embolism was established, and immunohistochemistry and polymerase chain reaction (PCR) were performed on tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) in plasma, and pulmonary embolism tissue. Plasma results: 1) t-PA levels: one hour following the initial modeling, the levels of t-PA in the modeling groups were significantly lower than those in the control group (P<0.05). In addition, the t-PA levels in the double PTE group were found to be lower after the modeling, as compared to the pre-modeling period (P<0.05). One hour after the second modeling, the double PTE group had lower t-PA levels compared to the control group (P<0.05). However, t-PA rebounded two hours after modeling in the double PTE group. One week after the second modeling, the double PTE group had higher t-PA levels compared to the other two groups (P<0.05). 2) PAI-1 results: one hour after the initial modeling, PAI-1 levels in the two modeling groups were lower compared to the pre-modeling period and control groups (P<0.05). Two hours following modeling, PAI-1 levels in both modeling groups were lower compared to the control group (P<0.05). PAI-1 levels were lower in the double PTE group one and two hours after the second modeling compared to the other two groups and pre-modeling period (P<0.05). 3) The immunohistochemistry results: the expression of PAI-1 decreased in the two modeling groups, while t-PA expression increased compared to the control group. 4) PCR results: t-PA mRNA expression did not differ among the three groups. The PAI-1 mRNA expression was lower in the two PTE groups compared to the control group. We conclude that in the early stages of PTE, the local fibrinolytic activity of the thrombus is increased, which is favorable for thrombolysis. However, as the thrombus persists, the activity of the fibrinolytic system is inhibited, contributing to the development of chronic thromboembolic pulmonary hypertension.
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Modelos Animales de Enfermedad , Fibrinólisis , Inhibidor 1 de Activador Plasminogénico , Embolia Pulmonar , Activador de Tejido Plasminógeno , Animales , Conejos , Embolia Pulmonar/metabolismo , Embolia Pulmonar/sangre , Embolia Pulmonar/patología , Inhibidor 1 de Activador Plasminogénico/metabolismo , Inhibidor 1 de Activador Plasminogénico/genética , Activador de Tejido Plasminógeno/metabolismo , Activador de Tejido Plasminógeno/genética , Masculino , ARN Mensajero/metabolismo , ARN Mensajero/genética , Pulmón/metabolismoRESUMEN
Laser-driven plasma accelerators provide tabletop sources of relativistic electron bunches and femtosecond x-ray pulses, but usually require petawatt-class solid-state-laser pulses of wavelength λL ~ 1 µm. Longer-λL lasers can potentially accelerate higher-quality bunches, since they require less power to drive larger wakes in less dense plasma. Here, we report on a self-injecting plasma accelerator driven by a long-wave-infrared laser: a chirped-pulse-amplified CO2 laser (λL ≈ 10 µm). Through optical scattering experiments, we observed wakes that 4-ps CO2 pulses with < 1/2 terawatt (TW) peak power drove in hydrogen plasma of electron density down to 4 × 1017 cm-3 (1/100 atmospheric density) via a self-modulation (SM) instability. Shorter, more powerful CO2 pulses drove wakes in plasma down to 3 × 1016 cm-3 that captured and accelerated plasma electrons to relativistic energy. Collimated quasi-monoenergetic features in the electron output marked the onset of a transition from SM to bubble-regime acceleration, portending future higher-quality accelerators driven by yet shorter, more powerful pulses.
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Objective: To report the clinical efficacy of adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures in patients with initially unresectable hepatocellular carcinoma. Methods: This is a retrospective case series study. Data from 100 patients who underwent adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures with long-term survival were collected from December 2018 to December 2022 at the Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese People's Liberation Army General Hospital. According to inclusion and exclusion criteria, 47 cases were included, among which patients who met the discontinuation criteria and maintained a drug-free tumor-free status. Thirty-nine male and eight female patients were included, with an age of (54.2±18.8)years(range:38 to 73 years) at initial diagnosis. At the time of initial diagnosis, 43 cases (91.5%) were classified as Barcelona Clinic Liver Cancer stage C. Survival curves were made using Kaplan Meier method. Results: Forty-seven patients underwent R0 resection, all achieved a drug-free tumor-free state through postoperative adjuvant therapy based on pathological examination results. Thirty-six patients(76.6%) maintained a drug-free tumor-free survival status for more than 6 months,28 patients(59.6%) for more than 12 months,and 8 patients(17.0%) for more than 24 months. The longest drug-free tumor-free survival in this cohort reached 48 months. The median follow-up time in this study was 32 months. After diagnosis, the overall survival rates at 1- and 3- years were 97.7%(95%CI:93.4% to 100%) and 90.7%(95%CI:82.5% to 99.8%). The postoperative recurrence-free survival rates at 1- and 3- years were 91.0%(95%CI:83.0% to 99.8%) and 71.3%(95%CI:58.7% to 86.5%). Conclusions: The adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical approach provides long-term survival benefits for patients with initially unresectable hepatocellular carcinoma. Standardized adjuvant therapy maybe sustain long-term tumor-free status,and achieve drug-free tumor-free survival.
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Carcinoma Hepatocelular , Inmunoterapia , Neoplasias Hepáticas , Humanos , Masculino , Femenino , Estudios Retrospectivos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/cirugía , Persona de Mediana Edad , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/cirugía , Adulto , Anciano , Terapia Combinada , Quimioterapia Adyuvante , Tasa de Supervivencia , HepatectomíaRESUMEN
Objective: To explore the value of optical coherence tomography (OCT) imaging system in evaluating cervical lesions in vivo. Methods: A total of 1 214 patients with cervical lesions were collected from January 2020 to December 2021 in the Third Affiliated Hospital of Zhengzhou University, Maternal and Chlid Heaith Hospital of Gushi County, Xinyang City, Henan Province, and Maternal and Chlid Heaith Hospital of Sui County, Shangqiu City, Henan Province. The age of the patients was (38.9±10.5) years (range: 16-77 years). All patients underwent in vivo cervical OCT examination and cervical biopsy pathology examination, and summarized the OCT image features of in vivo cervical lesions. Using the pathological diagnosis as the "gold standard", the accuracy, specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of OCT image interpretation results were evaluated, as well as the consistency of OCT image diagnosis and pathological diagnosis. At the same time, the in vivo cervical OCT imaging system, as a newly developed screening tool, was compared with the traditional combined screening of human papillomavirus (HPV) and Thinprep cytologic test (TCT), to assess the screening effect. Results: By comparing the OCT images of the cervix in vivo with the corresponding HE images, the OCT image characteristics of the normal cervix and various types of cervical lesions in vivo were summarized. The accuracy, sensitivity, specificity, PPV and NPV of OCT image in the diagnosis of high-grade squamous intraepithelial lesion (HSIL) and above (HSIL+) were 93.4%, 88.5%, 95.0%, 85.0% and 96.2%, respectively. The accuracy, sensitivity, specificity, PPV and NPV of OCT for low-grade squamous intraepithelial lesion (LSIL) were 84.7%, 61.7%, 96.3%, 89.3% and 83.2%, respectively. The consistency between OCT image diagnosis and pathological diagnosis was strong (Kappa value was 0.701).The accuracy, sensitivity and specificity of OCT screening, HPV and TCT combined screening were 83.7% vs 64.9% (χ²=128.82, P<0.001), 77.8% vs 64.5% (χ²=39.01, P<0.001), 91.8% vs 65.4% (χ²=98.12, P<0.001), respectively. The differences were statistically significant. Conclusions: OCT imaging system has high sensitivity and specificity in the evaluation of cervical lesions in vivo, and has the characteristics of non-invasive, real-time and high efficiency. OCT examination is expected to become an effective method for the diagnosis of cervical lesions and cervical cancer screening.
Asunto(s)
Cuello del Útero , Sensibilidad y Especificidad , Tomografía de Coherencia Óptica , Neoplasias del Cuello Uterino , Humanos , Femenino , Tomografía de Coherencia Óptica/métodos , Adulto , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/diagnóstico , Persona de Mediana Edad , Cuello del Útero/diagnóstico por imagen , Cuello del Útero/patología , Adolescente , Anciano , Displasia del Cuello del Útero/diagnóstico por imagen , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/diagnóstico , Infecciones por Papillomavirus/diagnóstico , Adulto Joven , Frotis Vaginal , Biopsia , Valor Predictivo de las Pruebas , Detección Precoz del Cáncer/métodosRESUMEN
We present a measurement of η production from neutrino interactions on argon with the MicroBooNE detector. The modeling of resonant neutrino interactions on argon is a critical aspect of the neutrino oscillation physics program being carried out by the DUNE and Short Baseline Neutrino programs. η production in neutrino interactions provides a powerful new probe of resonant interactions, complementary to pion channels, and is particularly suited to the study of higher-order resonances beyond the Δ(1232). We measure a flux-integrated cross section for neutrino-induced η production on argon of 3.22±0.84(stat)±0.86(syst) 10^{-41} cm^{2}/nucleon. By demonstrating the successful reconstruction of the two photons resulting from η production, this analysis enables a novel calibration technique for electromagnetic showers in GeV accelerator neutrino experiments.
RESUMEN
To explore the mechanism whereby cGAS-STING pathway regulates the pyroptosis of cryptorchidism cells, with a view to finding a new strategy for clinically treating cryptorchidism-induced infertility. Spermatogonial GC-1 cells were heat stimulated to simulate the heat hurt microenvironment of cryptorchidism. The cell viability was assayed by CCK-8, and cellular DNA damage was detected by gamma-H2AX immunofluo-rescence assay. Flow cytometry was employed to assess pyroptosis index, while western blot, ELISA and PCR were used to examine the expressions of pyroptosis-related proteins (Caspase-1, IL-1beta, NLRP3) and cGAS-STING pathway proteins (cGAS, STING). After STING silencing by siRNA, the expressions of pyroptosis-related proteins were determined. Pyroptosis occurred after heat stimulation of cells. Morphological detection found cell swelling and karyopyknosis. According to the gamma-H2AX immunofluorescence (IFA) assay, the endonuclear green fluorescence was significantly enhanced, the gamma-H2AX content markedly increased, and the endonuclear DNA was damaged. Flow cytometry revealed a significant increase in pyroptosis index. Western blot and PCR assays showed that the expressions of intracellular pyrogenic proteins like Caspase-1, NLRP3 and GSDMD were elevated. The increased STING protein and gene expressions in cGAS-STING pathway suggested that the pathway was intracellularly activated. Silencing STING protein in cGAS-STING pathway led to significantly inhibited pyroptosis. These results indicate that cGAS-STING pathway plays an important role in heat stress-induced pyroptosis of spermatogonial cells. After heat stimulation of spermatogonial GC-1 cells, pyroptosis was induced and cGAS-STING pathway was activated. This study can further enrich and improve the molecular mechanism of cryptorchidism.