RESUMEN
Pseudomonas aeruginosa (P. aeruginosa) typically forms biofilms in vivo, which exhibit high resistance and complicate eradication efforts. Additionally, persistent inflammation and excessive oxidative stress can lead to severe lung dysfunction, facilitating bacterial colonization and infection. Herein, we prepared oil-in-water (O/W) nanoemulsions (TD-αT NEs) by using PEG5k-block-PCL5k and α-tocopherol to encapsulate tobramycin (TOB). To enhance TOB's drug load, a hydrophobic ion pair (TDIP) composed of TOB and docosahexaenoic acid (DHA) was pre-prepared. TD-αT NEs was not only easily prepared and aerosolized, but stable in both physics and chemistry. The negatively charged TD-αT NEs facilitated penetration through mucus, reaching infection sites. Subsequently, TD-αT NEs permeated biofilms due to their small size and released drugs via lipase-triggered carrier dissociation, aiding in eradicating internal bacteria within biofilms (with a 16-fold reduction in CFU vs. free TOB group). TD-αT NEs simultaneously exerted superior anti-inflammatory effects, reducing levels of pro-inflammatory cytokines (NO, IL-6, IL-8, and TNF-α) while increasing the level of anti-inflammatory cytokine (IL-10). It was achieved through the upregulation of PPAR-γ and downregulation of NF-κB signaling, thus mitigating the lung damage. In addition, TD-αT NEs demonstrated strong antioxidant activity, alleviating the oxidative stress induced by P. aeruginosa. Notably, when administered via inhalation, TD-αT NEs significantly reduced the lung bacterial burden, lung inflammation, and oxidative stress in vivo compared to TOB solution. TD-αT NEs could prove beneficial in treating chronic pulmonary infections induced by P. aeruginosa through a comprehensive strategy, specifically enhancing biofilm eradication, reducing inflammation, and alleviating oxidative stress.
Asunto(s)
Antibacterianos , Biopelículas , Ácidos Docosahexaenoicos , Emulsiones , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Tobramicina , Pseudomonas aeruginosa/efectos de los fármacos , Tobramicina/farmacología , Tobramicina/química , Tobramicina/administración & dosificación , Emulsiones/química , Ácidos Docosahexaenoicos/química , Ácidos Docosahexaenoicos/farmacología , Ácidos Docosahexaenoicos/administración & dosificación , Animales , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Antibacterianos/farmacología , Antibacterianos/química , Biopelículas/efectos de los fármacos , Ratones , Pruebas de Sensibilidad Microbiana , Nanopartículas/química , Estrés Oxidativo/efectos de los fármacos , Tamaño de la PartículaRESUMEN
Vessel transplantation is currently considered the "gold standard" treatment for cardiovascular disease. However, ideal artificial vascular grafts should possess good biocompatibility and mechanical strength that match those of native autologous vascular tissue to promote in vivo tissue regeneration. In this study, a series of dynamic cross-linking double-network hydrogels and the resultant hydrogel tubes were prepared. The hydrogels (named PCO), composed of rigid poly(vinyl alcohol) (PVA), flexible carboxymethyl chitosan (CMCS), and a cross-linker of aldehyde-based ß-cyclodextrin (OCD), were formed in a double-network structure with multiple dynamical cross-linking including dynamic imine bonds, hydrogen bonds, and microcrystalline regions. The PCO hydrogels exhibited superior mechanical strength, good network stability, and fatigue resistance. Additionally, it demonstrated excellent cell and blood compatibility. The results showed that the introduction of CMCS/OCD led to a significant increase in the proliferation rate of endothelial cells seeded on the surface of the hydrogel. The hemolysis rate in the test was lower than 0.3%, and both protein adsorption and platelet adhesion were reduced, indicating an excellent anticoagulant function. The plasma recalcification time test results showed that endogenous coagulation was alleviated to some extent. When formed into blood vessels and incubated with blood, no thrombus formation was observed, and there was minimal red blood cell aggregation. Therefore, this novel hydrogel tube, with excellent mechanical properties, exhibits antiadhesive characteristics toward blood cells and proteins, as well as antithrombotic properties, making it hold tremendous potential for applications in the biomedical and engineering fields.
Asunto(s)
Materiales Biocompatibles , Quitosano , Hidrogeles , Alcohol Polivinílico , Hidrogeles/química , Hidrogeles/farmacología , Hidrogeles/síntesis química , Quitosano/química , Quitosano/análogos & derivados , Quitosano/farmacología , Humanos , Alcohol Polivinílico/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/síntesis química , Prótesis Vascular , Ensayo de Materiales , beta-Ciclodextrinas/química , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Hemólisis/efectos de los fármacos , Animales , Adhesividad Plaquetaria/efectos de los fármacos , Reactivos de Enlaces Cruzados/químicaRESUMEN
Continuing medical education plays a pivotal role in fostering and upholding the standard of excellence in medicine. Both SPOC (small private online course) and BOPPPS (bridge-in, learning objective, pretest, participatory learning, posttest, and summary) methodologies are rooted in the same educational and learning theories, emphasizing active student engagement, interaction, and feedback. Using ultrasound-guided spinal anesthesia as an exemplar, we aimed to investigate the feasibility of blended teaching (combination of BOPPPS and SPOC) for anesthesiology clinicians and explore trainees' and trainers' perspectives towards the innovative method. Twenty-seven attending anesthesiologists were randomly divided into experimental group (nâ =â 14, blended teaching method) and control group (nâ =â 13, traditional teaching method). The questionnaire was administered before and a week post-training. Their operative skills (measured by operation time) were assessed. The students' cognitive evaluation of the blended teaching mode was conducted in the experimental group. The experimental group demonstrated notably higher theoretical scores compared to the control group [(46.42â ±â 5.345) vs (41.92â ±â 5.219), tâ =â 2.213, Pâ <â .05]. The operation time in the experimental group was significantly shorter than that in the control group [(84.79â ±â 28.450) seconds vs (114.23â ±â 35.607) seconds, tâ =â -2.383, Pâ <â .05]. Most participants preferred blended learning as it was more effective than traditional learning. Suggestions for enhancement included enhanced online interactivity with trainers and the inclusion of case analysis. Integration of blended teaching incorporating BOPPPS and SPOC methodologies holds promise for enhancing the efficiency of skill training among anesthesiologists. Blended learning may become a viable and well-received option among anesthesia clinicians in China.
Asunto(s)
Anestesiología , Educación Médica Continua , Estudios de Factibilidad , Humanos , Anestesiología/educación , Educación Médica Continua/métodos , Masculino , Femenino , Adulto , Competencia Clínica , Anestesia Raquidea/métodos , Anestesiólogos/educación , Encuestas y Cuestionarios , Cuerpo Médico de Hospitales/educaciónRESUMEN
This study aims to investigate the role and underlying mechanisms of Sirt1 in the pathophysiological process of OA. Safranine O and HE staining were utilized to identify pathological changes in the cartilage tissue. Immunohistochemistry was employed to evaluate the expression levels of proteins. IL-1ß treatment and TamCartSirt1flox/flox mice were utilized to induce OA model both in vitro and in vivo. Key autophagy-related transcription factors, autophagy-related genes, and chondrocyte extracellular matrix (ECM) breakdown enzyme markers were examined using multi assays. Immunofluorescence staining revealed subcellular localization and gene expression patterns. ChIP assay and Co-immunoprecipitation assay were conducted to investigate the interactions between FoxO1 and the promoter regions of Atg7 and Sirt1. Our results demonstrate that Sirt1 deficiency exhibited inhibitory effects on ECM synthesis and autophagy, as well as exacerbated angiogenesis. Moreover, Atg7, Foxo1, and Sirt1 could form a protein complex. Sirt1 was observed to facilitate nuclear translocation of FoxO1, enhancing its transcriptional activity. Furthermore, FoxO1 was found to bind to the promoter regions of Atg7 and Sirt1, potentially regulating their expression. This study provides valuable insights into the involvement of Sirt1-Atg7-FoxO1 loop in OA, opening new avenues for targeted therapeutic interventions aiming to mitigate cartilage degradation and restore joint function.
Asunto(s)
Osteoartritis , Sirtuina 1 , Animales , Ratones , Autofagia , Cartílago/metabolismo , Condrocitos , Osteoartritis/metabolismo , Sirtuina 1/genética , Sirtuina 1/metabolismoRESUMEN
@#Objective The potential mechanism of curcumin(CUR)combined with berberine(BBR)in improving drug-induced liver injury(DILI)was preliminarily predicted by a method of in vivo experiment in combination with network pharmacology.Methods The animal model was established by acetaminophen(APAP)-induced DILI and the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were detected in serum of mice.The network pharmacological approach was used to collect related targets of CUR,BBR,and DILI;Wayne mapping was carried out to screen intersection targets,followed by establishment of a protein-protein interaction(PPI)network of CUR-BBR-DILI.Functional enrichment analysis of gene ontology(GO)and pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG)were conducted finally.Results The in vivo experimental results showed that the combination of CUR and BBR can significantly reduce the serum ALT and AST levels in mice,which is better than administration alone;Network pharmacology experiment results exhibited that 291 related targets of CUR and 208 related targets of BBR were collected by PharmMapper database,and 904 related targets of DILI were collected by Genecards database;77 intersection targets were screened by Venny 2.1.0 database;52 gene functions and 20 signal pathways possibly in connection with the improvement of DILI via drug combination were obtained by GO and KEGG analysis,respectively;nine of the top ten core targets according to degree in PPI network were enriched to PI3K/AKT signaling pathway,which were in order as follows:SRC,EGFR,HSP90AA1,IGF1,HRAS,MAPK14,ESR1,CASP3,and PTK2.Conclusion DILI might be synergistically improved by CUR combined BBR through multi-target and multi-pathway manner,providing a theoretical basis for the elucidation of the mechanism of drug combination against DILI.
RESUMEN
Wide-bandgap gallium nitride (GaN)-based semiconductors offer significant advantages over traditional Si-based semiconductors in terms of high-power and high-frequency operations. As it has superior properties, such as high operating temperatures, high-frequency operation, high breakdown electric field, and enhanced radiation resistance, GaN is applied in various fields, such as power electronic devices, renewable energy systems, light-emitting diodes, and radio frequency (RF) electronic devices. For example, GaN-based high-electron-mobility transistors (HEMTs) are used widely in various applications, such as 5G cellular networks, satellite communication, and radar systems. When a current flows through the transistor channels during operation, the self-heating effect (SHE) deriving from joule heat generation causes a significant increase in the temperature. Increases in the channel temperature reduce the carrier mobility and cause a shift in the threshold voltage, resulting in significant performance degradation. Moreover, temperature increases cause substantial lifetime reductions. Accordingly, GaN-based HEMTs are operated at a low power, although they have demonstrated high RF output power potential. The SHE is expected to be even more important in future advanced technology designs, such as gate-all-around field-effect transistor (GAAFET) and three-dimensional (3D) IC architectures. Materials with high thermal conductivities, such as silicon carbide (SiC) and diamond, are good candidates as substrates for heat dissipation in GaN-based semiconductors. However, the thermal boundary resistance (TBR) of the GaN/substrate interface is a bottleneck for heat dissipation. This bottleneck should be reduced optimally to enable full employment of the high thermal conductivity of the substrates. Here, we comprehensively review the experimental and simulation studies that report TBRs in GaN-on-SiC and GaN-on-diamond devices. The effects of the growth methods, growth conditions, integration methods, and interlayer structures on the TBR are summarized. This study provides guidelines for decreasing the TBR for thermal management in the design and implementation of GaN-based semiconductor devices.
RESUMEN
BACKGROUND: The Khorana risk score (KRS) has poor predictive value for cancer-associated thrombosis in a single tumor type but is associated with early all-cause mortality from cancer. Evidence for the association between KRS and all-cause mortality in Japanese patients with gastric and colorectal cancer is limited. AIM: To investigate whether KRS was independently related to all-cause mortality in Japanese patients with gastric and colorectal cancer after adjusting for other covariates and to shed light on its temporal validity. METHODS: Data from Dryad database were used in this study. Patients in the Gastroenterology Department of Sapporo General Hospital, Sapporo, Japan, were enrolled. The starting and ending dates of the enrollment were January 1, 2008 and January 5, 2015, respectively. The cutoff date for follow-up was May 31, 2016. The independent and dependent (target) variables were the baseline measured using the KRS and final all-cause mortality, respectively. The KRS was categorized into three groups: Low-risk group (= 0 score), intermediate-risk group (1-2 score), and high-risk group (≥ 3 score). RESULTS: Men and patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 2 displayed a higher 2-year risk of death than women and those with ECOG PS 0-1 in the intermediate/high risk group for KRS. The higher the score, the higher the risk of early death; however, the relevance of this independent prediction decreased with longer survival. The overall survival of each patient was recorded via real-world follow-up and retrospective observations, and this study yielded the overall relationship between KRS and all-cause mortality. CONCLUSION: The prechemotherapy baseline of KRS was independently associated with all-cause mortality within 2 years; however, this independent predictive relationship weakened as survival time increased.
RESUMEN
The Anthropocene is a new geologic epoch defined by the significant impact of human activity on the planet. Industrialisation and population growth have altered the natural environment. The logistics industry, which facilitates economic development and enhances human well-being, relies on logistic carriers as essential equipment. Pallets, the most representative tools of logistic carriers, transport more than 80 % of the world's trade. The conventional pallet market structure is largely determined by economic and convenience factors, but in light of the global environmental changes, the leading users of pallet products have raised their environmental standards, making environmental performance a key factor in the pallet industry. While China is the second largest pallet holder and accounts for 25 % of the global pallet holdings, it lacks an in-depth understanding on the pallet market structure, the environmental effects, and the barriers for developing pallet sharing system in China. This study conducts comprehensive field studies to reveal the pallet market structure in China, applies life cycle assessment to present a cradle to grave environmental evaluation of the five widely-used pallet material types that account for 99 % of market share, and compare various end-of-life treatment methods using scenario analysis. Results show that the current market structure does not align with the optimal environmental outcomes, but would be improved by establishing the circulation-sharing system. Therefore, there is an urgent need for the pallet industry to undergo a green transition. The focus for developing a sharing system should be on engaging the leading user enterprises in the supply chain, rather than merely relying on the pallet manufacturers who have limited bargaining power. Additionally, the environmental impacts can be reduced by 20 % to 300 % via choosing the appropriate end-of-life treatment method for each pallet material type.
RESUMEN
An oral galactosylated carboxymethyl chitosan polymeric nanomicelles (Gal-N-CMCS NPs) embedded in chitosan-alginate hydrogel (CA-Gel) was developed to load cyclosporine A (CyA) as therapeutic agents against ulcerative colitis (UC). Galactose modified CMCS with macrophage targeting characteristic and CyA via a simple ultrasonication method to form Gal-N-CMCS/CyA NPs, and mixed CA-Gel to acquire the final formulation (Gal-N-CMCS/CyA Gel). The generated Gal-N-CMCS/CyA NPs displayed a desirable particle size (206.8 nm), negative surface charge (-19.5 mV), and high encapsulating efficiency (89.6 %). The morphology and release profiles were also charactered by transmission electron microscope [1] and dialysis method, respectively. Strikingly, the mucus penetration of Gal-N-CMCS/CyA NPs exceeded 90 % within 90 min. The Gal-N-CMCS NPs internalized by macrophages were 3.3-fold higher than CMCS-N NPs, thereby, enhancing the anti-inflammatory activities of NPs. Meanwhile, these NPs exhibited excellent biocompatibility, reduced the toxic effect of CyA, and targeting ability on inflammatory macrophages both in vitro and in vivo. Most importantly, in vivo studies revealed that CyA NPs could efficiently target the inflamed colon, remarkably alleviate inflammation, repair mucosal and reconstructed colonic epithelial barriers in UC mice induced by dextran sulfate sodium (DSS) via Toll-like receptor 4 -Nuclear factor kappa-B (TLR4-NF-κB) pathway. Our findings suggest that these high-performance and facilely fabricated Gal-N-CMCS/CyA NPs could be developed as a promising drug carrier for oral UC treatment.
Asunto(s)
Quitosano , Colitis Ulcerosa , Nanopartículas , Animales , Ratones , Colitis Ulcerosa/tratamiento farmacológico , Ciclosporina , Polímeros , Sulfato de Dextran/efectos adversosRESUMEN
Background: The utilization of Propofol, a widely used intravenous sedative or anesthetic, is characterized by its quick onset, predictable control, and fleeting half-life during both general anesthesia and intensive care unit sedation. Recent evidence, however, has highlighted propofol's propensity to induce euphoria, particularly in patients undergoing painless procedures such as gastrointestinal or gastric endoscopy. Given its widespread use in patients undergoing such procedures, this study aims to investigate the clinical evidence and factors that may influence propofol-induced euphoria in these settings. Methods: The Addiction Research Center Inventory-Chinese Version (ARCI-CV) scale was administered to 360 patients undergoing gastric or gastrointestinal endoscopy using propofol as a sedative. Patient characteristics including past medical history, depression, anxiety, alcohol abuse, and sleep disturbance were recorded through history taking and assessment using various questionnaires prior to the examination. The euphoric and sedative statuses were assessed at 30 min and 1 week post-examination. Results: The experimental results of a survey of 360 patients who underwent gastric or gastrointestinal endoscopy using propofol showed that the mean Morphine-Benzedrine Group (MBG) score before the procedure and after 30 min of the procedure was 4.23 and 8.67, respectively. The mean Pentobarbital-Chlorpromazine-Alcohol Group (PCAG) score before the procedure and after 30 min of the procedure was 3.24 and 6.22, respectively. These results showed that both MBG and PCAG scores increased significantly after the procedure. Certain factors, such as dreaming, propofol dose, duration of anesthesia, and etomidate dose, were all correlated with MBG both at 30 min and 1 week after the examination. In addition, etomidate had an effect of decreasing MBG scores and increasing PCAG scores both at 30 min and 1 week after the examination. Conclusion: Taken together, propofol may elicit euphoria and potentially contribute to propofol addiction. There are several risk factors for the development of propofol addiction, including dreaming, propofol dose, duration of anesthesia, and etomidate dose. These findings suggest that propofol may have a euphoric effect and may have the potential for drug addiction and abuse.
RESUMEN
Purpose: Investigating the changes of regional homogeneity (ReHo) values and both static and dynamic functional connectivity (FC) before and after Traditional Chinese Manual Therapy (Tuina) in patients with lumbar disk herniation (LDH) through resting-state functional magnetic resonance imaging (RS-fMRI). Based on this, we observe the effect of Tuina on the above abnormal changes. Methods: Patients with LDH (n = 27) and healthy controls (HCs) (n = 28) were recruited. The functional magnetic resonance imaging (fMRI) scanning was performed two times in LDH patients, before Tuina (time point 1, LDH-pre) and after the sixth Tuina (time point 2, LDH-pos). And for one time in HCs which received no intervention. The ReHo values were compared between LDH-pre and HCs. The significant clusters detected by ReHo analysis were selected as seeds to calculate static functional connectivity (sFC). We also applied the sliding-window to perform dynamic functional connectivity (dFC). To evaluate the Tuina effect, the mean ReHo and FC values (both static and dynamic) were extracted from significant clusters and compared between LDH and HCs. Results: In comparison to HCs, LDH patients displayed decreased ReHo in the left orbital part middle frontal gyrus (LO-MFG). For sFC analysis, no significant difference was found. However, we found decreased dFC variance between LO-MFG and the left Fusiform, and increased dFC variance in the left orbital inferior frontal gyrus and left precuneus. Both ReHo and dFC values revealed after Tuina, the brain activities in LDH patients were similar to HCs. Conclusion: The present study characterized the altered patterns of regional homogeneity in spontaneous brain activity and those of functional connectivity in patients with LDH. Tuina can reshape the function of the default mode network (DMN) in LDH patients, which may contribute to the analgesic effect of Tuina in LDH patients.
RESUMEN
BACKGROUND: Automated segmentation techniques for cardiac magnetic resonance imaging (MRI) are beneficial for evaluating cardiac functional parameters in clinical diagnosis. However, due to the characteristics of unclear image boundaries and anisotropic resolution anisotropy produced by cardiac magnetic resonance imaging technology, most of the existing methods still have the problems of intra-class uncertainty and inter-class uncertainty. However, due to the irregularity of the anatomical shape of the heart and the inhomogeneity of tissue density, the boundaries of its anatomical structures become uncertain and discontinuous. Therefore, fast and accurate segmentation of cardiac tissue remains a challenging problem in medical image processing. METHODOLOGY: We collected cardiac MRI data from 195 patients as training set and 35patients from different medical centers as external validation set. Our research proposed a U-net network architecture with residual connections and a self-attentive mechanism (Residual Self-Attention U-net, RSU-Net). The network relies on the classic U-net network, adopts the U-shaped symmetric architecture of the encoding and decoding mode, improves the convolution module in the network, introduces skip connections, and improves the network's capacity for feature extraction. Then for solving locality defects of ordinary convolutional networks. To achieve a global receptive field, a self-attention mechanism is introduced at the bottom of the model. The loss function employs a combination of Cross Entropy Loss and Dice Loss to jointly guide network training, resulting in more stable network training. RESULTS: In our study, we employ the Hausdorff distance (HD) and the Dice similarity coefficient (DSC) as metrics for assessing segmentation outcomes. Comparsion was made with the segmentation frameworks of other papers, and the comparison results prove that our RSU-Net network performs better and can make accurate segmentation of the heart. New ideas for scientific research. CONCLUSION: Our proposed RSU-Net network combines the advantages of residual connections and self-attention. This paper uses the residual links to facilitate the training of the network. In this paper, a self-attention mechanism is introduced, and a bottom self-attention block (BSA Block) is used to aggregate global information. Self-attention aggregates global information, and has achieved good segmentation results on the cardiac segmentation dataset. It facilitates the diagnosis of cardiovascular patients in the future.
Asunto(s)
Benchmarking , Corazón , Humanos , Anisotropía , Entropía , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia MagnéticaRESUMEN
Two-dimensional nanomaterial-based membranes have earned broad attention because of their excellent capability of separation performance in a mixture that can challenge the conventional membrane materials utilized in the organic solvent nanofiltration (OSN) field. Boron nitride (BN) nanosheet membranes have displayed superb stability and separation ability in aqueous and organic solutions compared to the widely researched analogous graphene-based membranes; nevertheless, the concentration polarization of organic dye pollutants fades their separation performance and eclipses their potential adoption as a feasible technology. Herein, PDDA-modified BN (PBN) and sodium alginate-modified BN (SBN) nanosheet membranes with a thinner laminar structure are facially fabricated to improve the molecule separation performance compared to that of the pristine BN membrane. In aqueous separation application, the SBN membranes (2 µm) can reject positively charged dyes up to 100% and the PBN membrane (2 µm) could reject negatively charged dyes up to 100%. Impressively, the PBN membranes (3 µm) and SBN membranes (3 µm) demonstrate record high performances in OSN, with a permeance of 809 L m-2 h-1 bar-1 and 97.71% rejection to acid fuchsin in acetonitrile and 290 L m-2 h-1 bar-1 and 94.94% rejection to Azure B in dimethyl sulfoxide, respectively. The charged PBN and SBN nanosheet membranes demonstrate stable separation capability, exhibiting their potential for practical water and organic solvent purification processes.
RESUMEN
To implement strict environmental targets in China's cement industry into small regions, one should evaluate the city-level eco-efficiency that provides comprehensive instruction. This study establishes a plant-level database with 4000+ production lines located in 341 cities, calculates the energy consumption and CO2, SO2, NOx, and PM emissions, evaluates the eco-efficiency in each city via Slacks-based Measure, and verifies the spatial features of these indicators. Results show that the energy consumption and emissions of the industry are highly concentrated, with ~10 % of the land area contributing to 28.4 %-34.6 % of the total amounts in 2019. The average eco-efficiency value of the clinker calcination and cement grinding processes are 0.761 and 0.714, but the city clusters having low eco-efficiency values are inconsistent with the ones having large energy consumption and emission amounts. The results can contribute to the implementation of the targets such as carbon peaking and pollution cap in China's cement industry.
RESUMEN
Background: The emergence of immune checkpoint inhibitors (ICIs) has brought about a paradigm shift in the treatment landscape of non-small cell lung cancer (NSCLC). Despite the promising long-term survival outcomes and optimization of pathological complete response (cPR) demonstrated by various studies such as Impower010 and Checkmate-816, the effectiveness of neoadjuvant immunotherapy in advanced resectable NSCLC remains a subject of debate. Although previous research has explored the connection between the efficacy of neoadjuvant therapy and surgical-related safety, limited studies have specifically investigated the surgical-related safety of neoadjuvant immunotherapy. Therefore, our study aims to assess the efficacy and surgical-related safety of neoadjuvant immunotherapy in advanced resectable non-small cell lung cancer. Method: We conducted a retrospective study on a cohort of 93 patients with stage IIIA-IIIC NSCLC who underwent neoadjuvant therapy and surgical resection. Among them, 53 patients received neoadjuvant immunotherapy, 18 patients underwent neoadjuvant chemotherapy while the remaining 22 underwent neoadjuvant targeted therapy. The patients were separated into further groups according to their pathological type. Data analyses were performed using Mann-Whitney U test, chi-square test. Results: All patients were categorized into six distinct groups. Notably, the neoadjuvant immunotherapy squamous carcinoma group exhibited a favorable edge over the neoadjuvant targeted squamous carcinoma group concerning the duration of drainage tube indwelling and the extent of lymph node dissection. Furthermore, the neoadjuvant immunotherapy adenocarcinoma group outperformed neoadjuvant targeted therapy adenocarcinoma counterpart in terms of achieving complete pathological response (cPR). Simultaneously, the neoadjuvant immunotherapy adenocarcinoma group surpassed the neoadjuvant chemotherapy adenocarcinoma group in the incidence of hydrothorax. Nevertheless, no statistically significant disparities were noted between the neoadjuvant immunotherapy squamous carcinoma group and the neoadjuvant chemotherapy carcinoma group. Conclusion: Regarding surgical outcomes, neoadjuvant immunotherapy conferred notable advantages compared to conventional neoadjuvant chemotherapy and neoadjuvant targeted therapy for patients diagnosed with adenocarcinoma. In the case of squamous carcinoma, neoadjuvant immunotherapy exhibited superiority over neoadjuvant targeted therapy, although additional evidence is required to conclusively establish its precedence over neoadjuvant chemotherapy.
RESUMEN
Purpose: The aim of this study was to develop a radiomics nomogram based on grayscale ultrasound (US) for preoperatively predicting Lymphovascular invasion (LVI) in patients with pathologically confirmed T1 (pT1) breast invasive ductal carcinoma (IDC). Methods: One hundred and ninety-two patients with pT1 IDC between September 2020 and August 2022 were analyzed retrospectively. Study population was randomly divided in a 7: 3 ratio into a training dataset of 134 patients (37 patients with LVI-positive) and a validation dataset of 58 patients (19 patients with LVI-positive). Clinical information and conventional US (CUS) features (called clinic_CUS features) were recorded and evaluated to predict LVI. In the training dataset, independent predictors of clinic_CUS features were obtained by univariate and multivariate logistic regression analyses and incorporated into a clinic_CUS prediction model. In addition, radiomics features were extracted from the grayscale US images, and the radiomics score (Radscore) was constructed after radiomics feature selection. Subsequent multivariate logistic regression analysis was also performed for Radscore and the independent predictors of clinic_CUS features, and a radiomics nomogram was developed. The performance of the nomogram model was evaluated via its discrimination, calibration, and clinical usefulness. Results: The US reported axillary lymph node metastasis (LNM) (US_LNM) status and tumor margin were determined as independent risk factors, which were combined for the construction of clinic_CUS prediction model for LVI in pT1 IDC. Moreover, tumor margin, US_LNM status and Radscore were independent predictors, incorporated as the radiomics nomogram model, which achieved a superior discrimination to the clinic_CUS model in the training dataset (AUC: 0.849 vs. 0.747; P < 0.001) and validation dataset (AUC: 0.854 vs. 0.713; P = 0.001). Calibration curve for the radiomic nomogram showed good concordance between predicted and actual probability. Furthermore, decision curve analysis (DCA) confirmed that the radiomics nomogram had higher clinical net benefit than the clinic_CUS model. Conclusion: The US-based radiomics nomogram, incorporating tumor margin, US_LNM status and Radscore, showed a satisfactory preoperative prediction of LVI in pT1 IDC patients.
RESUMEN
BACKGROUND: There are some techniques for disassembly of hard nuclear. It is challenging in hard cataract surgery through microincision. The classic chop or prechop techniques often do not succeed,resulting in incomplete nuclear segmentation. The authors describe a new chop technique for removing hard nucleus cataracts in coaxial microincisional cataract surgery. METHODS: We create a deep hole (drill) in the central nucleus with the phaco tip and divide the nucleus (prechop) with the Nagahara chopper and the modified capsulorhexis forceps inside the hole. The chopper and the modified capsulorhexis forceps are spread apart laterally after they approach at the center of the nucleus, to create a complete fracture across the entire nucleus. Since January 2022, we have completed 27 eyes of 25 patients with hard nucleus cataract using this technique. RESULTS: Complete segmentation of the hard nuclear into two hemispheres was implemented with this drill and prechop technique in all cases. The effective phaco time and ultrasound energy decreased. No intraoperative complication such as iris injury, anterior capsule tears, zonulysis, or posterior capsule rupture with vitreous loss occurred during surgery. CONCLUSIONS: This technique simplifies the previous prechop techniques especially for hard nucleus in microincisional cataract surgery. The technique is efficient, safe and simple.
Asunto(s)
Extracción de Catarata , Catarata , Oftalmología , Humanos , Capsulorrexis , IrisRESUMEN
Purpose: Lumbar disc herniation (LDH) is one of the leading causes of low-back pain and results in a series of clinical symptoms, including pain, reflex loss, and muscle weakness. Spinal manipulative therapy (SMT) can relieve pain and promote internal and external stabilization of the lumbar spine. In this study, we investigated whether the brain alterations of LDH patients with SMT were frequency-dependent based on the calculation of Amplitude of Low-Frequency Fluctuations (ALFF) and fractional ALFF (fALFF). Further, we established a cohort of LDH patients to evaluate the contribution of SMT treatments to brain functional reorganization. Methods: A total of 55 participants, including 27 LDH patients and 28 health controls (HCs), were collected. All LDH patients underwent two fMRI scans (before SMT and after the sixth SMT session). To represent LDH-related brain oscillatory activities, we calculated the ALFF and fALFF in the conventional band (0.01-0.08 Hz), the slow-4 band (0.027-0.073 Hz), and the slow-5 band (0.01-0.027 Hz). Moreover, we extracted ALFF and fALFF values in clusters with significant differences to evaluate the SMT effect. Results: Compared with HCs, the LDH patients before SMT (LDH-pre) exhibited increased fALFF in right lingual gyri in the conventional band, and showed increased fALFF in left Cerebelum_Crus1 in the slow-4 band. We further examined the abnormal brain activities changes before and after the SMT intervention. The ALFF and fALFF values of LDH-pre group were higher than those of the HCs and LDH-pos groups. After SMT, the increased ALFF and fALFF values were suppressed for patients in conventional band and slow-4 band. Conclusion: The present study characterized the altered regional patterns in spontaneous neural activity in patients with LDH. Meanwhile, SMT is an effective treatment of LDH, and we supposed that it might have been involved in modulating dysfunctional brain regions which are important for the processing of pain. The findings of the current study may provide new insights to understand pathological mechanism of LDH.
RESUMEN
BACKGROUND: The revised-Risk Analysis Index (RAI-rev) can accurately predict postoperative mortality risk. However, the association of RAI-rev with composite outcome of major morbidity and mortality (MMM) among older surgical patients is largely unknown. This study investigated the association between RAI-rev and postoperative MMM in older patients undergoing abdominal surgery. It also assessed the predictive value of RAI-rev combined with other preoperative risk factors. METHODS: This retrospective cohort study reviewed the medical records of all patients aged 65 and older who underwent abdominal surgery between January 2018 and December 2019. The primary outcome was the postoperative MMM during hospitalization, and its association with preoperative RAI-rev scores was assessed using multivariable logistic regression analysis. The prediction of postoperative outcomes was used the receiver-operating characteristic curve analysis. RESULTS: A total of 2225 older patients were analyzed, and 258 (11.6%) developed postoperative MMM. After adjusting for confounders, each unit increase in RAI-rev scores resulted in a 2.3% increase in the MMM risk and a 3.0% increase in the odds of life-threatening complications and mortality (both P < 0.05). The area under the curves (AUCs) of RAI-rev scores in predicting MMM and life-threatening complications and mortality was 0.604 (95% CI: 0.567 to 0.640) and 0.633 (95% CI: 0.592 to 0.675), respectively (both P < 0.001); when the RAI-rev was combined with age, gender, American Society of Anesthesiologists (ASA) classification, operative stress, and urgency status of surgery (emergency or elective), the AUCs were 0.694 (95% CI: 0.659 to 0.729) and 0.739 (95% CI: 0.702 to 0.777), respectively (both P < 0.001). CONCLUSIONS: Higher RAI-rev scores were independently associated with increased risk of MMM. When combined with age, gender, ASA classification, operative stress, and urgency status of surgery, RAI-rev had improved performance in predicting the risk of MMM, particularly the life-threatening complications and mortality.