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The dispersive sweep of fast radio bursts (FRBs) has been used to probe the ionized baryon content of the intergalactic medium1, which is assumed to dominate the total extragalactic dispersion. Although the host-galaxy contributions to the dispersion measure appear to be small for most FRBs2, in at least one case there is evidence for an extreme magneto-ionic local environment3,4 and a compact persistent radio source5. Here we report the detection and localization of the repeating FRB 20190520B, which is co-located with a compact, persistent radio source and associated with a dwarf host galaxy of high specific-star-formation rate at a redshift of 0.241 ± 0.001. The estimated host-galaxy dispersion measure of approximately [Formula: see text] parsecs per cubic centimetre, which is nearly an order of magnitude higher than the average of FRB host galaxies2,6, far exceeds the dispersion-measure contribution of the intergalactic medium. Caution is thus warranted in inferring redshifts for FRBs without accurate host-galaxy identifications.
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Fast radio bursts (FRBs) are millisecond-duration radio transients1,2 of unknown origin. Two possible mechanisms that could generate extremely coherent emission from FRBs invoke neutron star magnetospheres3-5 or relativistic shocks far from the central energy source6-8. Detailed polarization observations may help us to understand the emission mechanism. However, the available FRB polarization data have been perplexing, because they show a host of polarimetric properties, including either a constant polarization angle during each burst for some repeaters9,10 or variable polarization angles in some other apparently one-off events11,12. Here we report observations of 15 bursts from FRB 180301 and find various polarization angle swings in seven of them. The diversity of the polarization angle features of these bursts is consistent with a magnetospheric origin of the radio emission, and disfavours the radiation models invoking relativistic shocks.
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Our current knowledge of cosmic star-formation history during the first two billion years (corresponding to redshift z > 3) is mainly based on galaxies identified in rest-frame ultraviolet light1. However, this population of galaxies is known to under-represent the most massive galaxies, which have rich dust content and/or old stellar populations. This raises the questions of the true abundance of massive galaxies and the star-formation-rate density in the early Universe. Although several massive galaxies that are invisible in the ultraviolet have recently been confirmed at early epochs2-4, most of them are extreme starburst galaxies with star-formation rates exceeding 1,000 solar masses per year, suggesting that they are unlikely to represent the bulk population of massive galaxies. Here we report submillimetre (wavelength 870 micrometres) detections of 39 massive star-forming galaxies at z > 3, which are unseen in the spectral region from the deepest ultraviolet to the near-infrared. With a space density of about 2 × 10-5 per cubic megaparsec (two orders of magnitude higher than extreme starbursts5) and star-formation rates of 200 solar masses per year, these galaxies represent the bulk population of massive galaxies that has been missed from previous surveys. They contribute a total star-formation-rate density ten times larger than that of equivalently massive ultraviolet-bright galaxies at z > 3. Residing in the most massive dark matter haloes at their redshifts, they are probably the progenitors of the largest present-day galaxies in massive groups and clusters. Such a high abundance of massive and dusty galaxies in the early Universe challenges our understanding of massive-galaxy formation.
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Lateral growth of thin films is crucial for organic electronic devices, such as field-effect transistors. Here, we report a strategy to improve the lateral growth of pentacene films using rubrene as a surfactant-like additive. Atomic force microscopy (AFM) images confirm the enhanced lateral growth with the presence of rubrene, resulting in smooth and enlarged molecule domains in the films in comparison to those without rubrene. Molecular dynamics simulations are conducted to explore the interlayer diffusion of pentacene molecules during the growth. With the rubrene molecules as surfactant-like additives, mean square displacement (MSD) analysis shows that the pentacene molecules have a descending diffusion coefficient of 2.0 × 10-5 cm2 s-1, which is greater than the ascending diffusion coefficient of 1.6 × 10-5 cm2 s-1. The more descending molecules lead to an enhanced lateral growth of pentacene films, which is in good agreement with the experiments. As a result, the pentacene films grown with rubrene exhibit a rapid increase in carrier mobility over thickness due to the well-connected domains resulting from enhanced lateral growth. This finding will provide a new strategy to modulate the morphology of organic films for high-performance devices.
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OBJECTIVE: To assess the efficacy and safety of iguratimod in adult patients with active axial spondyloarthritis (axSpA). METHOD: This randomized, double-blind, placebo-controlled clinical trial lasted for 28 weeks. Patients with axSpA were randomized 1:1 to receive iguratimod 25 mg twice daily or a placebo. All patients also took celecoxib 200 mg twice daily for the first 4 weeks and on demand from 4 to 28 weeks. The primary endpoints were ASAS20 at 4 weeks and the non-steroidal anti-inflammatory drug (NSAID) index at 28 weeks. Other assessment variables included ASAS40, ASAS5/6 response rates, Spondyloarthritis Research Consortium of Canada (SPARCC) scores, and adverse events. RESULTS: In total, 35 patients completed the study and were included for analyses. The median (interquartile range) NSAID index was 43.8 (34.9-51.8) in the iguratimod group, which is significantly lower than 68.9 (42.5-86.4) in the placebo group (p = 0.025). ASAS response rates and changes in disease activity scores were similar between the iguratimod and placebo groups. Patients in the iguratimod group had more improvement in median (interquartile range) SPARCC scores for sacroiliac joints than did those in the placebo group [71% (54-100%) vs 40% (0-52%), p = 0.006]. Iguratimod combined with celecoxib was not associated with a greater risk of adverse effects than was monotherapy with celecoxib. No severe adverse events occurred. CONCLUSIONS: In the treatment of active axSpA, iguratimod has a potential NSAID-sparing effect, and may also reduce magnetic resonance imaging-assessed bone marrow oedema in sacroiliac joints. Iguratimod provides an additional treatment option for patients with active axSpA.Clinical trial registration numberChiCTR2000029112, Chinese Clinical Trial Registry (http://www.chictr.org.cn).
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AIM: To develop an aggregate model that integrated clinical data, habitat characteristics, and intratumoral and peritumoral features to assess the risk categorization of thymomas. MATERIALS AND METHODS: We retrospectively analyzed 140 thymoma patients (70 low-risk and 70 high-risk), including pathological data. The patients were randomly divided into training cohort (n = 114) and test cohort (n = 26). The k-means clustering was utilized to partition the primary tumor into habitats based on intratumoral radiomic features, 6 distinct habitats were identified. By expanding the region of interest (ROI) mask, 2 peritumoral regions were obtained. Finally, 7 clinical characteristics, 3 habitat values, 20 radiomic features were utilized to develop an aggregated model, to predict the risk of thymoma. Shapley additive explanations (SHAP) interpretation was used for features importance ranking. The accuracy and area under curve (AUC) were used to analyze the performance of the models. RESULTS: The aggregated model, which utilized the XGBoost classifier, demonstrated the best performance with an AUC of 0.811 and an accuracy of 0.769. In comparison, the radiomic model produced an AUC of 0.654 and an accuracy of 0.692. Additionally, the Intratumoral + peritumoral model exhibited an AUC of 0.728 and an accuracy of 0.769. CONCLUSION: Our study establishes a novel tool to predict the risk of thymoma with a good performance. If prospectively validated, the model may refine thymoma patient selection for risk-adaptative therapy and improve prognosis.
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Timoma , Neoplasias del Timo , Humanos , Masculino , Femenino , Neoplasias del Timo/diagnóstico por imagen , Timoma/diagnóstico por imagen , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Adulto , Anciano , Tomografía Computarizada por Rayos X/métodosRESUMEN
AIMS: Alcoholic cardiomyopathy (ACM) is recognized as a type of non-ischemic dilated cardiomyopathy (DCM). To date, the clinical prognosis of ACM remains a topic of debate in previous studies and there are limited studies on its cardiac MRI characteristics. The aim of this study was to summarize the clinical and MRI features of ACM patients and to identify the predictors of adverse prognosis based on clinical characteristics and MRI imaging findings. MATERIALS AND METHODS: Adult patients who were clinically diagnosed with ACM and underwent enhanced CMR between September 2015 and August 2022 were retrospectively enrolled. The primary endpoints were major adverse cardiovascular events, including cardiac-related death, heart transplantation, hospitalization for heart failure and life-threatening ventricular arrhythmias (sustained ventricular tachycardia, ventricular fibrillation, or ICD shock). The risk factors associated with these primary end points were identified using multivariable Cox analysis. RESULTS: A total of 62 ACM patients (50 ± 9 years, 62 men) were included. The majority of patients presented with symptoms of heart failure. Over a median follow-up period of 30.3 months (IQR 12.2-57.7 months), 24 patients reached the primary endpoints. For clinical variables, multivariable analysis showed that drinking duration (HR=1.05; 95%CI:1.01, 1.11; p=0.03) and persistent drinking (HR=3.71; 95%CI:1.46, 9.44; p=0.01) were associated with MACE. For CMR variables, late gadolinium enhancement (LGE) percent (HR = 1.09; 95% CI: 1.03, 1.14; p<0.001) stood out as an independent predictor for MACE. CONCLUSIONS: In ACM patients, persistent drinking and cardiac MRI-defined myocardial scar were associated with adverse outcomes such as cardiac death, heart transplantation, hospitalization for heart failure or life-threatening ventricular arrhythmias.
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Cardiomiopatía Alcohólica , Imagen por Resonancia Magnética , Humanos , Masculino , Persona de Mediana Edad , Femenino , Cardiomiopatía Alcohólica/diagnóstico por imagen , Pronóstico , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Factores de Riesgo , Imagen por Resonancia Cinemagnética/métodos , Medios de Contraste , AdultoRESUMEN
OBJECTIVE: Acute intracerebral hemorrhage (AICH) and cerebral cavernous hemangioma (CCM) are two common cerebral hemorrhage diseases with partially overlapping CT findings and clinical symptoms, making it hard to distinguish between them. The current study used histogram analysis based on CT images to differentiate between CCM and AICH and test its diagnosis performance. METHODS: This retrospective study included 158 patients with CCM and 137 patients with AICH. The histograms of brain CT plain scan images of both groups were extracted using Python code and included 18 histogram parameters of the lesions. The most effective parameters were selected by univariate logistic regression analysis and Spearman correlation analysis and included in the final multivariate logistic regression model. The sample was randomly divided into the training set and the validation set by 7:3. The ROC curve was constructed to evaluate the discriminant efficiency of the final logistic regression model in distinguishing between AICH and CCM. RESULTS: The univariate analysis identified seven significant histogram parameters with the following final logistic regression model: F = 3.731 + 2.6411 × 10-9 × Energy-1.192 × Kurtosis-0.003 × Minimum-1.449 × Skewness + 2.5002 × 10-10 × Total Energy-1.103 × Uniformity+0.009 × Variance. The model showed good diagnostic performance in distinguishing between AICH and CCM, with an AUC of 0.876, sensitivity of 70.8%, and specificity of 91.9% in the training set, and an AUC of 0.870, sensitivity of 82.9%, and specificity of 85.1% in the validation set. CONCLUSIONS: The histogram analysis of brain CT images can be used as an auxiliary method to distinguish between AICH and CCM effectively.
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PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease, with a worldwide prevalence of 25%. Although numerous clinical trials have been conducted over the last few decades, an effective treatment has not been approved yet. Extensive research has accumulated a large amount of data and experience; however, the vast number of clinical trials and new therapeutic targets for NAFLD make it impossible to keep abreast of the relevant information. Therefore, a systematic analysis of the existing trials is necessary. METHODS: Here, we reviewed clinical trials on NAFLD registered in the mandated federal database, ClinicalTrials.gov, to generate a detailed overview of the trials related to drugs and therapeutic targets for NAFLD treatment. Following screening for pertinence to therapy, a total of 440 entries were identified that included active trials as well as those that have already been completed, suspended, terminated, or withdrawn. RESULTS: We summarize and systematically analyze the state, drug development pipeline, and discovery of treatment targets for NAFLD. We consider possible factors that may affect clinical outcomes. Furthermore, we discussed these results to explore the mechanisms responsible for clinical outcomes. CONCLUSION: We summarised the landscape of current clinical trials and suggested the directions for future NAFLD therapy to assist internal medicine specialists in treating the whole clinical spectrum of this highly prevalent liver disease.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Resultado del Tratamiento , Ensayos Clínicos como AsuntoRESUMEN
PURPOSE: Maternal hyperandrogenism during pregnancy is associated with adverse gestational outcomes and chronic non-communicable diseases in offspring. However, few studies are reported to demonstrate the association between maternal androgen excess and cardiac health in offspring. This study aimed to explore the relation between androgen exposure in utero and cardiac health of offspring in fetal and adult period. Its underlying mechanism is also illustrated in this research. METHODS: Pregnant mice were injected with dihydrotestosterone (DHT) from gestational day (GD) 16.5 to GD18.5. On GD18.5, fetal heart tissue was collected for metabolite and morphological analysis. The hearts from adult offspring were also collected for morphological and qPCR analysis. H9c2 cells were treated with 75 µM androsterone. Immunofluorescence, flow cytometry, qPCR, and western blot were performed to observe cell proliferation and explore the underlying mechanism. RESULTS: Intrauterine exposure to excessive androgen led to thinner ventricular wall, decreased number of cardiomyocytes in fetal offspring and caused cardiac hypertrophy, compromised cardiac function in adult offspring. The analysis of steroid hormone metabolites in fetal heart tissue by ultra performance liquid chromatography and tandem mass spectrometry showed that the content of androgen metabolite androsterone was significantly increased. Mechanistically, H9c2 cells treated with androsterone led to a significant decrease in phosphorylated retinoblastoma protein (pRB) and cell cycle-related protein including cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), and cyclin D1 (CCND1) in cardiomyocytes. This resulted in cell cycle arrest at G1-S phase, which in turn inhibited cardiomyocyte proliferation. CONCLUSION: Taken together, our results indicate that in utero exposure to DHT, its metabolite androsterone could directly decrease cardiomyocytes proliferation through cell cycle arrest, which has a life-long-lasting effect on cardiac health. Our study highlights the importance of monitoring sex hormones in women during pregnancy and the follow-up of cardiac function in offspring with high risk of intrauterine androgen exposure.
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Andrógenos , Miocitos Cardíacos , Humanos , Adulto , Embarazo , Femenino , Animales , Ratones , Andrógenos/efectos adversos , Androsterona , Puntos de Control del Ciclo Celular , Proliferación Celular , Proteínas de Ciclo Celular , Dihidrotestosterona , Cardiomegalia/inducido químicamenteRESUMEN
PURPOSE: There is little information on factors that influence the glycemic variability (GV) during the nocturnal and diurnal periods. We aimed to examine the relationship between clinical factors and GV during these two periods. METHODS: This cross-sectional study included 134 patients with type 2 diabetes. 24-h changes in blood glucose were recorded by a continuous glucose monitoring system. Nocturnal and diurnal GV were assessed by standard deviation of blood glucose (SDBG), coefficient of variation (CV), and mean amplitude of glycemic excursions (MAGE), respectively. Robust regression analyses were performed to identify the factors associated with GV. Restricted cubic splines were used to determine dose-response relationship. RESULTS: During the nocturnal period, age and glycemic level at 12:00 A.M. were positively associated with GV, whereas alanine aminotransferase was negatively associated with GV. During the diurnal period, homeostatic model assessment 2-insulin sensitivity (HOMA2-S) was positively associated with GV, whereas insulin secretion-sensitivity index-2 (ISSI2) was negatively associated with GV. Additionally, we found a J-shape association between the glycemic level at 12:00 A.M. and MAGE, with 9.0 mmol/L blood glucose level as a cutoff point. Similar nonlinear associations were found between ISSI2 and SDBG, and between ISSI2 and MAGE, with ISSI2 value of 175 as a cutoff point. CONCLUSION: Factors associated with GV were different between nocturnal and diurnal periods. The cutoff points we found in this study may provide the therapeutic targets for beta-cell function and pre-sleep glycemic level in clinical practice.
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Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucemia/análisis , Estudios Transversales , Automonitorización de la Glucosa Sanguínea , Resistencia a la Insulina/fisiologíaRESUMEN
PURPOSE: To examine the effect of diabetes, duration of diabetes, and blood glucose on speech-, low/mid-, and high-frequency hearing loss. METHODS: In this cross-sectional study, 2821 participants aged 20-87 years in the China National Health Survey were included. Diabetes was defined as valid fasting blood glucose (FBG) of ≥ 7.0 mmol/L, a self-reported history of diabetes or the use of anti-diabetic medications. Speech-(500, 1000, 2000, and 4000 Hz), low/mid- (500, 1000 and 2000 Hz), and high-frequency (4000, 6000, and 8000 Hz) hearing loss was defined as pure tone average of responding frequencies > 20 dB HL in the better ear, respectively. RESULTS: In fully adjusted models, for speech-, low/mid-, and high-frequency hearing loss, compared with no diabetes, those with diabetes (OR[95%CI]: 1.44 [1.12, 1.86], 1.23 [0.94, 1.61], and 1.75 [1.28, 2.41], respectively) and with diabetes for > 5 years duration (OR[95%CI]: 1.63 [1.09, 2.42], and 1.63 [1.12, 2.36], 2.15 [1.25, 3.70], respectively) were at higher risk. High FBG level was associated with a higher risk of speech-, low/ mid-, and high-frequency hearing loss. And there were stronger associations between HL and diabetes, longer duration and higher in "healthier population" (no hypertension, no dyslipidemia and younger age). CONCLUSION: Diabetes, longer duration, and higher FBG level were independently associated with hearing loss for speech-, low/mid- and high-frequency hearing loss, particularly in higher frequency and "healthier population". Paying more attention to hearing loss in those populations could lower the burden of hearing loss.
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BACKGROUND: The aim was to validate the correlation between corneal shape parameters and axial length growth (ALG) during orthokeratology using Image-Pro Plus (IPP) 6.0 software. METHODS: This retrospective study used medical records of myopic children aged 8-13 years (n = 104) undergoing orthokeratology. Their corneal topography and axial length were measured at baseline and subsequent follow-ups after lens wear. Corneal shape parameters, including the treatment zone (TZ) area, TZ diameter, TZ fractal dimension, TZ radius ratio, eccentric distance, pupil area, and pupillary peripheral steepened zone(PSZ) area, were measured using IPP software. The impact of corneal shape parameters at 3 months post-orthokeratology visit on 1.5-year ALG was evaluated using multivariate linear regression analysis. RESULTS: ALG exhibited significant associations with age, TZ area, TZ diameter, TZ fractal dimension, and eccentric distance on univariate linear regression analysis. Multivariate regression analysis identified age, TZ area, and eccentric distance as significantly correlated with ALG (all P < 0.01), with eccentric distance showing the strongest correlation (ß = -0.370). The regressive equation was y = 1.870 - 0.235a + 0.276b - 0.370c, where y represents ALG, a represents age, b represents TZ area, and c represents eccentric distance; R2 = 0.27). No significant relationships were observed between the TZ radius ratio, pupillary PSZ area, and ALG. CONCLUSIONS: IPP software proves effective in capturing precise corneal shape parameters after orthokeratology. Eccentric distance, rather than age or the TZ area, significantly influences ALG retardation.
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Cristalino , Niño , Humanos , Estudios Retrospectivos , Topografía de la Córnea , Análisis Multivariante , Programas InformáticosRESUMEN
OBJECTIVES: The present study aims to develop an effective risk-prediction score (RPS) to improve screening efficiency and contribute to secondary prevention of colorectal cancer (CRC). STUDY DESIGN: Screening for colorectal lesions. METHODS: 14,398 high-risk individuals aged 50-65 years were included. The baseline characteristics of participants with and without colorectal lesions (CL) were compared using a Chi-squared test. The overall population was randomly split into a training set and a test set in the ratio of 80% and 20%. One-factor and multifactor logistic regression analyses were performed in the training set to construct the RPS (scores of 0-9.62). Area under curve (AUC) was calculated as an estimate of predictive performance using the receiver-operating characteristic (ROC) curve in the test set. RESULTS: In the study population, being male, advanced age, current or previous smoking, weekly alcohol consumption, high body mass index (BMI ≥24 kg/m2), and previously detected colonic polyp were associated with higher risk of CL. Compared to the low-risk group (0-2.31 points), the ORs and 95% confidence intervals (CIs) for the moderate-risk group (2.31-3.85 points) and high-risk group (3.85-8.42 points) were 1.58 (1.44, 1.73) and 2.52 (2.30, 2.76), respectively. For every 1-point increase in score, participants had a 27% increased risk of CL (OR:1.27, 95% CI: 1.24, 1.30). For participants with CL predicted by RPS, the area under the working characteristic curve was 0.61 (P < 0.001). CONCLUSION: Our RPS can quickly and efficiently identify multiple lesions of the colorectum. Combining RPS with existing screening strategies facilitates the identification of very high-risk individuals and may help to prevent CRC.
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BACKGROUND: Epithelial-mesenchymal transition (EMT) plays a crucial role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the involvement of small extracellular vesicles (sEVs) in EMT and their contributions to CRSwNP has not been extensively investigated. METHODS: SEVs were isolated from nasal mucosa through ultracentrifugation. MicroRNA sequencing and reverse-transcription quantitative polymerase chain reaction were employed to analyze the differential expression of microRNAs carried by sEVs. Human nasal epithelial cells (hNECs) were used to assess the EMT-inducing effect of sEVs/microRNAs. EMT-associated markers were detected by western blotting and immunofluorescence. Dual-luciferase reporter assay was performed to determine the target gene of miR-375-3p. MicroRNA mimic, lentiviral, and plasmid transduction were used for functional experiments. RESULTS: In line with the greater EMT status in eosinophilic CRSwNP (ENP), sEVs derived from ENP (ENP-sEVs) could induce EMT in hNECs. MiR-375-3p was elevated in ENP-sEVs compared to that in control and nonENP. MiR-375-3p carried by ENP-sEVs facilitated EMT by directly targeting KH domain containing RNA binding (QKI) at seed sequences of 913-919, 1025-1033, and 2438-2444 in 3â™-untranslated region. Inhibition of QKI by miR-375-3p overexpression promoted EMT, which could be reversed by restoration of QKI. Furthermore, the abundance of miR-375-3p in sEVs was closely correlated with the clinical symptom score and disease severity. CONCLUSIONS: MiR-375-3p-enriched sEVs facilitated EMT by suppressing QKI in hNECs. The association of miR-375-3p with disease severity underscores its potential as both a diagnostic marker and a therapeutic target for the innovative management of CRSwNP.
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Transición Epitelial-Mesenquimal , Vesículas Extracelulares , MicroARNs , Pólipos Nasales , Rinitis , Sinusitis , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Sinusitis/genética , Sinusitis/patología , Pólipos Nasales/genética , Pólipos Nasales/patología , Pólipos Nasales/metabolismo , Vesículas Extracelulares/metabolismo , Rinitis/genética , Rinitis/patología , Rinitis/metabolismo , Enfermedad Crónica , Mucosa Nasal/patología , Mucosa Nasal/metabolismo , Masculino , Femenino , RinosinusitisRESUMEN
Lymph node metastasis status stands as a pivotal prognostic indicator in forecasting the outlook for breast cancer patients. Consequently, precise evaluation of this status holds paramount importance in the staging, treatment, and prognosis of breast cancer. The utilization of radiomics, genomics, proteomics, transcriptomics, and histopathology methodologies has notably enhanced the precision of lymph node metastasis status prediction in breast cancer. This review provides an overview of recent advancements in omics-based lymph node metastasis prediction for breast cancer, elucidating the significance of various omics prediction models and integrated multi-omics models in this predictive endeavor. The overarching goal is to augment the accuracy of preoperative lymph node metastasis status prediction in breast cancer, thereby aiding clinicians in the selection of efficacious personalized treatment strategies, while concurrently averting undertreatment of patients with a heightened risk of metastasis.
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Neoplasias de la Mama , Genómica , Metástasis Linfática , Proteómica , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/genética , Femenino , Proteómica/métodos , Pronóstico , Ganglios Linfáticos/patología , Ganglios Linfáticos/metabolismo , Transcriptoma , MultiómicaRESUMEN
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 , Inmunoglobulina G , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Glucocorticoides/uso terapéutico , Linfocitos , Inmunoglobulina ERESUMEN
Objective: To evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib and tislelizumab in the treatment of unresectable intrahepatic cholangiocarcinoma (ICC). Methods: The clinical data of 12 patients with unresectable ICC who received HAIC combined with lenvatinib and tislelizumab in the First Affliated Hospital of Soochow University from October 2021 to April 2023 were retrospectively analyzed. HAIC included gemcitabine plus oxaliplatin; this regimen was combined with lenvatinib and tislelizumab within 3-7 days after its initial administration. Relevant laboratory examinations were performed before each cycle of HAIC, and enhanced computed tomography/magnetic resonance imaging examinations were performed every 6-9 weeks. Tumor response to treatment was evaluated using the modified Response Evaluation Criteria in Solid Tumors. The objective response rate, disease control rate, progression-free survival, overall survival, and treatment-related adverse reactions of patients with ICC were statistically analyzed. Results: The objective response rate to HAIC combined with lenvatinib and tislelizumab was 6/12; the disease control rate was 8/12; the median progression-free survival was 11.8 months; and the median overall survival was 14.2 months. Three patients had grade â £ adverse reactions (increased alanine aminotransferase and aspartate aminotransferase thrombocytopenia), while three patients had grade â ¢ adverse reactions (increased total bilirubin, alanine aminotransferase, and aspartate aminotransferase). The remaining patients had grade â -â ¡ adverse reactions. There were no serious complications related to interventional surgery. Conclusions: Use of HAIC (gemcitabine plus oxaliplatin) combined with lenvatinib and tislelizumab in the treatment of unresectable ICC may be safe and feasible. Preliminary clinical studies have shown that this combination can improve the survival and prognosis of patients with ICC.
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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de los Conductos Biliares , Colangiocarcinoma , Compuestos de Fenilurea , Quinolinas , Humanos , Colangiocarcinoma/tratamiento farmacológico , Quinolinas/administración & dosificación , Quinolinas/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/uso terapéutico , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Masculino , Femenino , Infusiones Intraarteriales , Gemcitabina , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Persona de Mediana Edad , Oxaliplatino/administración & dosificación , Oxaliplatino/uso terapéutico , Arteria Hepática , Anciano , Resultado del TratamientoRESUMEN
Objective: To investigate the role of the Abdominal Aortic Calcification-8 (AAC-8) scoring system in predicting restenosis or occlusion of lower extremity arteries after dilatation and angioplasty with drug-coated balloon (DCB). Methods: In this retrospective study, 62 patients who underwent dilatation and angioplasty with DCB for lower limb atherosclerotic obliterans (ASO) were enrolled from September 2018 to June 2022 in Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School. Among them who aged (73.9±11.3) years, 37 were males and 25 were females. Patients were divided into two groups according to the condition of the lower extremity arteries after dilatation and angioplasty with DCB: recurrence group (n=26) and patency group (n=36). Logistic regression was used to analyze the factors associated with restenosis or occlusion of lower extremity arteries after dilatation and angioplasty with DCB. The predictive value of the AAC-8 score for restenosis or occlusion of the lower extremity arteries after dilatation and angioplasty with DCB was analyzed using the receiver operating characteristic curves (ROC curves). Results: The postoperative follow-up was 16.30 (10.97, 24.10) months in the patency group and 9.03 (6.98, 15.31) months in the recurrence group. The results of multifactorial logistic regression analysis showed that an elevated AAC-8 score (OR=1.388, 95%CI: 1.067-1.806, P=0.015) was an associated factor of restenosis or occlusion of the lower extremity arteries after dilatation and angioplasty with DCB. The ROC curve analysis showed that the area under the curve (AUC) of the AAC-8 score for predicting restenosis or occlusion of the lower extremity arteries after dilatation and angioplasty with DCB was 0.687 (95%CI: 0.550-0.824, P=0.013), with a cut-off value of 5.5 points, a sensitivity of 65.4% and a specificity of 69.5%. Conclusions: Elevated AAC-8 score is associated with restenosis or occlusion of the lower extremity arteries after dilatation and angioplasty with DCB. When the cut-off value is 5.5, the AAC-8 score predicts restenosis or occlusion of the lower extremity arteries after DCB dilation and angioplasty with a sensitivity of 65.4% and a specificity of 69.5%.
Asunto(s)
Angioplastia de Balón , Enfermedad Arterial Periférica , Masculino , Femenino , Humanos , Dilatación , Estudios Retrospectivos , Resultado del Tratamiento , Angioplastia , Arteria Femoral/cirugía , Arteria Poplítea/cirugía , Extremidad InferiorRESUMEN
Objective: To investigate the clinical effect of over-the-top (OTT) reconstruction of the anterior cruciate ligament (ACL) combined with the modified Lemaire technique in one-stage ACL revision. Methods: It's a retrospective study. The clinical data of 37 patients who underwent one-stage revision of ACL using OTT combined with modified Lemaire technique from April 2020 to May 2023 in the Department of Sports Medicine of Xinhua Hospital Affiliated to Dalian University were retrospectively analyzed. There were 28 males and 9 females with a mean age of (32.7±5.7) years. The postoperative knee function and surgical revision effect were evaluated by subjective and objective evaluation indexes of the knee joint before and 3 months and 24 months after surgery. The subjective evaluation indexes included the International Knee Documentation Committee (IKDC) score, Lysholm score, and Tegner score; and the objective evaluation indexes included the anterior-posterior static displacement distance of the tibia, tibia-femur relative rotation angle, the Lachman test, the axial shift test, and the ratio of the loss of muscle strength of the lower limb. Results: At the final follow-up, all patients returned to pre-injury motor level, with significant improvements in IKDC scores (45.3±6.8 preoperatively, 67.5±4.7 and 93.2±2.3 at 3 months and 2 years after the operation, respectively), Lysholm scores (57.2±2.6 preoperatively, 72.6±2.9 and 89.7±3.7 at 3 months and 2 years after the operation, respectively), and Tegner scores (3.1±0.7 preoperatively, 4.9±0.6 and 5.8±1.3 at 3 months and 2 years after the operation, respectively) (all P<0.001). The anterior-posterior static displacement distance of the tibia reduced significantly [from (5.2±0.5) mm before the operation to (1.4±0.5) mm at 2 years postoperatively) (P<0.001)]; and the relative rotation angle of the tibia-femur restored to the normal physiological range, it was reduced from 6.2°±1.2° before the operation to 1.7°±0.3° 2 years after (P<0.001). The Lachman test and axial shift test at 2 years postoperatively were all negative. The muscle strength loss ratio of the affected lower limb was significantly better than that before the operation (P<0.001). Conclusion: The use of OTT reconstruction combined with modified Lemaire technique for revision of ACL in patients with ACL reconstruction failure can circumvent the tunnel problem for one-stage revision and better restore the stability and function of the knee joint, with ideal clinical results.