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Colorectal cancer (CRC) has been becoming one of the most common causes of cancer mortality worldwide. Accumulating studies suggest that the progressive up-regulation of Wnt/ß-catenin signaling is a crucial hallmark of CRC, and suppressing it is a promising strategy to treat CRC. Herein, we reported our latest efforts in the discovery of novel fused tetrahydroisoquinoline derivatives with good anti-CRC activities by screening our in-house berberine-like library and further structure-activity relationship (SAR) studies, in which we identified compound 10 is a potent lead compound with significant antiproliferation potencies. By the biotinylated probe and LC-MS/MS study, Hsp90 was identified as its molecular target, which is a fully different mechanism of action from what we reported before. Further studies showed compound 10 directly engaged the N-terminal site of Hsp90 and promoted the degradation of ß-catenin, thereby suppressing the Wnt/ß-catenin signaling. More importantly, compound 10 exhibits favorable pharmacokinetic parameters and significant anti-tumor efficacies in the HCT116 xenograft model. Taken together, this study furnished the discovery of candidate drug compound 10 possessing a novel fused tetrahydroisoquinoline scaffold with excellent in vitro and in vivo anti-CRC activities by targeting Hsp90 to disturb Wnt/ß-catenin signaling pathway, which lay a foundation for discovering more effective CRC-targeted therapies.
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Antineoplásicos , Proliferação de Células , Neoplasias Colorretais , Ensaios de Seleção de Medicamentos Antitumorais , Tetra-Hidroisoquinolinas , Via de Sinalização Wnt , beta Catenina , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Tetra-Hidroisoquinolinas/farmacologia , Tetra-Hidroisoquinolinas/química , Tetra-Hidroisoquinolinas/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Relação Estrutura-Atividade , Animais , Proliferação de Células/efeitos dos fármacos , beta Catenina/metabolismo , beta Catenina/antagonistas & inibidores , Camundongos , Estrutura Molecular , Relação Dose-Resposta a Droga , Camundongos Nus , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/metabolismo , Camundongos Endogâmicos BALB CRESUMO
Immune checkpoint blockade has led to breakthroughs in the treatment of advanced gastric cancer. However, the prominent heterogeneity in gastric cancer, notably the heterogeneity of the tumor microenvironment, highlights the idea that the antitumor response is a reflection of multifactorial interactions. Through transcriptomic analysis and dynamic plasma sample analysis, we identified a metabolic "face-off" mechanism within the tumor microenvironment, as shown by the dual prognostic significance of nicotinamide metabolism. Specifically, macrophages and fibroblasts expressing the rate-limiting enzymes nicotinamide phosphoribosyltransferase and nicotinamide N-methyltransferase, respectively, regulate the nicotinamide/1-methylnicotinamide ratio and CD8+ T cell function. Mechanistically, nicotinamide N-methyltransferase is transcriptionally activated by the NOTCH pathway transcription factor RBP-J and is further inhibited by macrophage-derived extracellular vesicles containing nicotinamide phosphoribosyltransferase via the SIRT1/NICD axis. Manipulating nicotinamide metabolism through autologous injection of extracellular vesicles restored CD8+ T cell cytotoxicity and the anti-PD-1 response in gastric cancer.
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Macrófagos , Niacinamida , Nicotinamida Fosforribosiltransferase , Neoplasias Gástricas , Microambiente Tumoral , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Humanos , Macrófagos/metabolismo , Niacinamida/análogos & derivados , Niacinamida/farmacologia , Nicotinamida Fosforribosiltransferase/metabolismo , Animais , Camundongos , Fibroblastos/metabolismo , Nicotinamida N-Metiltransferase/metabolismo , Linhagem Celular Tumoral , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia , Feminino , Masculino , Vesículas Extracelulares/metabolismoRESUMO
A significant challenge in direct seawater electrolysis is the rapid deactivation of the cathode due to the large scaling of Mg(OH)2. Herein, we synthesized a Pt-coated highly disordered NiCu alloy (Pt-NiCu alloy) electrode with superior solidophobic behavior, enabling stable hydrogen generation (100 mA cm-2, >1000 h durability) and simultaneous production of Mg(OH)2 (>99.0% purity) in electrolyte enriched with Mg2+ and Ca2+. The unconventional solidophobic property primarily stems from the high surface energy of the NiCu alloy substrate, which facilitates the adsorption of surface water and thereby compels the bulk formation of Mg(OH)2 via homogeneous nucleation. The discovery of this solidophobic electrode will revolutionarily simplify the existing techniques for seawater electrolysis and increase the economic viability for seawater electrolysis.
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The urgent global health problem of antimicrobial resistance (AMR) calls for the discovery of new antibiotics with innovative modes of action while considering the low toxicity to mammalian cells. This paper proposes a novel strategy for designing antibiotics with selective bacterial toxicity by exploiting the positional differences of electron transport chains (ETC) in bacterial and mammalian cells. The focus is on cytochrome c (cyt C) and its maturation system in E. coli. The catalytic oxidative activity of metallophthalocyanine (MPc), which have a distinctive M-N4 structure, is being investigated. Unlike previous applications based on light-activated reactive oxygen species (ROS) generation, this study exploits the ability of MPcs to oxidize Fe2+ to Fe3+ in cyt C and catalyze the formation of disulfide bonds between cysteine residues to interfere with cyt C maturation, disrupt the bacterial respiratory chain and selectively kills bacteria. In contrast, in mammalian cells, these MPcs are located in the lysosomes and cannot access the ETC in the mitochondria, thus achieving selective bacterial toxicity. Two MPcs that showed effective antibacterial activity in a wound infection model were identified. This study provides a valuable reference for the design of novel antibiotics based on M-N4-based metal complex molecules.
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Antibacterianos , Escherichia coli , Indóis , Antibacterianos/farmacologia , Antibacterianos/química , Escherichia coli/efeitos dos fármacos , Indóis/química , Indóis/farmacologia , Animais , Citocromos c/metabolismo , Citocromos c/química , Isoindóis , Humanos , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Espécies Reativas de Oxigênio/metabolismo , OxirreduçãoRESUMO
OBJECTIVE: This study uses a two-sample Mendelian randomization (MR) analysis to delineate the causal influence of gut microbiota on the occurrence of irritable bowel syndrome (IBS), concurrently assessing the potential mediating function of depression within this framework. METHODS: Several two-sample MR methods were used to assess the causal repercussions of gut microbiota on the onset of both IBS and depression. Following this, gut microbiota and depression, which demonstrated notable causal associations, were integrated as exposure variables in a multivariable Mendelian randomization (MVMR) framework to construct a model encompassing gut microbiota, depression, and IBS. Mediation effects were assessed by examining the indirect pathway of gut microbiota â depression â IBS. RESULTS: Two-sample MR analysis unveiled a statistically significant causal association (P < 0.05) between specific bacterial group within the gut microbiota, notably p_Actinobacteria(OR = 0.829225), c_Clostridia(OR = 0.798897), s_Desulfovibrio_piger(OR = 1.163912), g_Streptococcus(OR = 1.132735), c_Actinobacteria(OR = 0.829224), and the onset of IBS. In the MVMR analysis, the relationship between depression and IBS was significant across Model 3, Model 7, Model 8, and Model 13 (P < 0.05). Assessment of mediation effects revealed that c_Clostridia and o_Clostridiales indirectly impacted IBS through depression, with masking effect ratios of 168.46 % and 168.44 %, respectively. CONCLUSION: These findings underscore a resilient causal association between the composition of gut microbiota and the initiation of IBS. Furthermore, depression serves as a mediator for particular groups of gut bacteria, thereby contributing to the development of IBS. These observations imply that interventions targeting mental health may potentially alleviate the risk of IBS onset attributable to adverse configurations of gut microbiota.
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Depressão , Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Análise da Randomização Mendeliana , Síndrome do Intestino Irritável/microbiologia , Humanos , Depressão/microbiologiaRESUMO
Optical waveguides fabricated in single crystals offer crucial passive/active optical components for photonic integrated circuits. Single crystals possess inherent advantages over their amorphous counterpart, such as lower optical losses in visible-to-mid-infrared band, larger peak emission cross-section, higher doping concentration. However, the writing of Type-I positive refractive index modified waveguides in single crystals using femtosecond laser technology presents significant challenges. Herein, this work introduces a novel femtosecond laser direct writing technique that combines slit-shaping with an immersion oil objective to fabricate low-loss Type-I waveguides in single crystals. This approach allows for precise control of waveguide shape, size, mode-field, and refractive index distribution, with a spatial resolution as high as 700 nm and a high positive refractive index variation on the order of 10-2, introducing new degrees of freedom to design and fabricate passive/active optical waveguide devices. As a proof-of-concept, this work successfully produces a 7 mm-long circular-shaped gain waveguide (≈10 µm in diameter) in an Er3+-doped YAG single crystal, exhibiting a propagation loss as low as 0.23 dB cm-1, a net gain of ≈3 dB and a polarization-insensitive character. The newly-developed technique is theoretically applicable to arbitrary single crystals, holding promising potential for various applications in integrated optics, optical communication, and photonic quantum circuits.
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BACKGROUND: Colorectal cancer (CRC) continues to be a major global health challenge, ranking as a top cause of cancer-related mortality. Alarmingly, the five-year survival rate for CRC patients hovers around a mere 10-30 %. The disruption of fibroblast growth factor receptor (FGFRs) signaling pathways is significantly implicated in the onset and advancement of CRC, presenting a promising target for therapeutic intervention in CRC management. Further investigation is essential to comprehensively elucidate FGFR1's function in CRC and to create potent therapies that specifically target FGFR1. PURPOSE: This study aims to demonstrate the oncogenic role of FGFR1 in colorectal cancer and to explore the potential of ß,ß-dimethylacrylalkannin (ß,ß-DMAA) as a therapeutic option to inhibit FGFR1. METHODS: In this research, we employed a comprehensive suite of techniques including tissue array, kinase profiling, computational docking, knockdown assay to predict and explore the inhibitor of FGFR1. Furthermore, we utilized kinase assay, pull-down, cell proliferation tests, and Patient derived xenograft (PDX) mouse models to further investigate a novel FGFR1 inhibitor and its impact on the growth of CRC. RESULTS: In our research, we discovered that FGFR1 protein is markedly upregulated in colorectal cancer tissues, suggesting a significant role in regulating cellular proliferation, particularly in patients with colorectal cancer. Furthermore, we conducted a computational docking, kinase profiling analysis, simulation and identified that ß,ß-DMAA could directly bind with FGFR1 within ATP binding pocket domain. Cell-based assays confirmed that ß,ß-DMAA effectively inhibited the proliferation of colon cancer cells and also triggered cell cycle arrest, apoptosis, and altered FGFR1-mediated signaling pathways. Moreover, ß,ß-DMAA effectively attenuated the development of PDX tumors in mice that were FGFR1-positive, with no notable toxicity observed. In summary, our study highlights the pivotal role of FGFR1 in colorectal cancer, suggesting that inhibiting FGFR1 activity could be a promising strategy for therapeutic intervention. We present strong evidence that targeting FGFR1 with ß,ß-DMAA is a viable approach for the management of colorectal cancer. Given its low toxicity and high efficacy, ß,ß-DMAA, as an FGFR1 inhibitor, warrants further investigation in clinical settings for the treatment of FGFR1-positive tumors.
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Proliferação de Células , Neoplasias Colorretais , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos , Animais , Feminino , Humanos , Camundongos , Acrilamidas/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Simulação de Acoplamento Molecular , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Amino acids are the building blocks of proteins and are widely used as important ingredients for other nitrogen-containing molecules. Here, we report the sustainable production of amino acids from biomass-derived hydroxy acids with high activity under visible-light irradiation and mild conditions, using atomic ruthenium-promoted cadmium sulfide (Ru1/CdS). On a metal basis, the optimized Ru1/CdS exhibits a maximal alanine formation rate of 26.0â molAla â gRu -1 â h-1, which is 1.7â times and more than two orders of magnitude higher than that of its nanoparticle counterpart and the conventional thermocatalytic process, respectively. Integrated spectroscopic analysis and density functional theory calculations attribute the high performance of Ru1/CdS to the facilitated charge separation and O-H bond dissociation of the α-hydroxy group, here of lactic acid. The operando nuclear magnetic resonance further infers a unique "double activation" mechanism of both the CH-OH and CH3-CH-OH structures in lactic acid, which significantly accelerates its photocatalytic amination toward alanine.
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Aminoácidos , Biomassa , Compostos de Cádmio , Rutênio , Sulfetos , Sulfetos/química , Rutênio/química , Compostos de Cádmio/química , Catálise , Aminoácidos/química , Processos Fotoquímicos , Teoria da Densidade Funcional , LuzRESUMO
Diatomic-site catalysts (DASCs) inherit the excellent performance of single-atom catalysts (SACs) by utilizing two adjacent atomic metal species to achieve functional complementarity and synergistic effects that improve the carbon dioxide reduction reaction (CO2RR) and H2 evolution reaction (HER) kinetics. Herein, we report a method to further improve the catalytic efficiency of Pt by using Pt and Ru single atoms randomly anchored on a g-C3N4 surface, yielding partial Pt-Ru dimers. The synthesized catalyst exhibits extraordinary photocatalytic activity and stability in both the CO2RR and HER processes. In-depth experimentation, the pH-dependent chemical exchange saturation transfer (CEST) imaging nuclear magnetic resonance (NMR) method, and theoretical analyses reveal that the excellent performance is attributed to orbital coupling between the Pt atoms and the neighboring Ru atoms (mainly dxy and dxz), which decreases the orbital energy levels and weakens the bond strength with intermediates, resulting in improved CO2RR and HER performance. This study successfully applies the pH-dependent CEST imaging NMR method to catalytic reactions, and CO2 adsorption is directly observed using CEST 2D imaging maps. This work presents significant potential for a variety of catalytic reaction applications by systematically designing bimetallic dimers with higher activity and stability.
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Accurate prediction of cattle weight is essential for enhancing the efficiency and sustainability of livestock management practices. However, conventional methods often involve labor-intensive procedures and lack instant and non-invasive solutions. This study proposed an intelligent weight prediction approach for cows based on semantic segmentation and Back Propagation (BP) neural network. The proposed semantic segmentation method leveraged a hybrid model which combined ResNet-101-D with the Squeeze-and-Excitation (SE) attention mechanism to obtain precise morphological features from cow images. The body size parameters and physical measurements were then used for training the regression-based machine learning models to estimate the weight of individual cattle. The comparative analysis methods revealed that the BP neural network achieved the best results with an MAE of 13.11 pounds and an RMSE of 22.73 pounds. By eliminating the need for physical contact, this approach not only improves animal welfare but also mitigates potential risks. The work addresses the specific needs of welfare farming and aims to promote animal welfare and advance the field of precision agriculture.
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Metal halide perovskite (MHP) structures that exhibit polarized photoluminescence (PL) have attracted significant interest in fabricating light field regulation elements for display, imaging, and information storage applications. We report a three-dimensional direct lithography of heterostructures for controllable polarized PL inside glass by laser-induced localized temperature engineering. The heterostructures consisted of oriented periodic structures (OPSs) and MHP nanocrystals, and the mechanism for hierarchical distribution of heterostructures was illustrated. The patterning of heterostructures for manipulable polarized PL can be used for information encryption, wave-plate, and polarized micro-LEDs.
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It has been well-established that light-matter interactions, as manifested by diverse linear and nonlinear optical (NLO) processes, are mediated by real and virtual particles, such as electrons, phonons, and excitons. Polarons, often regarded as electrons dressed by phonons, are known to contribute to exotic behaviors of solids, from superconductivity to photocatalysis, while their role in materials' NLO response remains largely unexplored. Here, the NLO response mediated by polarons supported by a model ionic metal oxide, TiO2, is examined. It is observed that the formation of polaronic states within the bandgap results in a dramatic enhancement of NLO absorption coefficient by over 130 times for photon energies in the sub-bandgap regions, characterized by a 100 fs scale ultrafast response that is typical for thermalized electrons in metals. The ultrafast polaronic NLO response is then exploited for the development of all-optical switches for ultrafast pulse generation in near-infrared (NIR) fiber lasers and modulation of optical signal in the telecommunication band based on evanescent interaction on a planar waveguide chip. These results suggest that the polarons supported by dielectric ionic oxides can fill the gaps left by dielectric and metallic materials and serve as a novel platform for nonlinear photonic applications.
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High-gain materials and high-quality structures are the two main conditions that determine the amplification performance of optical waveguides. However, it has been hard to balance each other, to date. In this work, we demonstrate breakthroughs in both glass optical gain and optical waveguide structures. We propose a secondary melting dehydration technique that prepares high-quality Er3+-Yb3+ co-doped phosphate glass with low absorption loss. Additionally, we propose a femtosecond laser direct-writing technique that allows controlling the cross section, size, and mode field of waveguides written in glass with high accuracy, leveraging submicron-resolution multi-scan direct-writing optical waveguide technology, which is beneficial for reducing insertion loss. As a proof of concept demonstration, we designed and fabricated two kinds of waveguides, namely, LP01- and LP11-mode waveguides in the Er3+-Yb3+ co-doped phosphate glass, enabling insertion loss as low as 0.9â dB for a waveguide length of 2 mm. Remarkably, we successfully achieved an optical amplification for both the waveguides with a net gain of >7â dB and a net-gain coefficient of >3.5â dB/mm, which is approximately one order of magnitude larger than that in the Er3+-Yb3+ co-doped phosphate glass fabricated by the traditional melt-quenching method. This will open new avenues toward the development of integrated photonic chips.
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BACKGROUND: The optimal multimorbidity measures for predicting disability trajectories are not universally agreed upon. We developed a multimorbidity index among middle-aged and older community-dwelling Chinese adults and compare its predictive ability of disability trajectories with other multimorbidity measures. METHODS: This study included 17,649 participants aged ≥50 years from the China Health and Retirement Longitudinal Survey 2011-2018. Two disability trajectory groups were estimated using the total disability score differences calculated between each follow-up visit and baseline. A weighted index was constructed using logistic regression models for disability trajectories based on the training set (70 %). The index and the condition count were used, along with the pattern identified by the latent class analysis to measure multimorbidity at baseline. Logistic regression models were used in the training set to examine associations between each multimorbidity measure and disability trajectories. C-statistics, integrated discrimination improvements, and net reclassification indices were applied to compare the performance of different multimorbidity measures in predicting disability trajectories in the testing set (30 %). RESULTS: In the newly developed multimorbidity index, the weights of the chronic conditions varied from 1.04 to 2.55. The multimorbidity index had a higher predictive performance than the condition count. The condition count performed better than the multimorbidity pattern in predicting disability trajectories. LIMITATION: Self-reported chronic conditions. CONCLUSIONS: The multimorbidity index may be considered an ideal measurement in predicting disability trajectories among middle-aged and older community-dwelling Chinese adults. The condition count is also suggested due to its simplicity and superior predictive performance.
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Pessoas com Deficiência , Multimorbidade , Pessoa de Meia-Idade , Humanos , Idoso , Estudos Longitudinais , Vida Independente , Doença CrônicaRESUMO
Based on previous findings, collateral circulation in the brain is vital in mitigating cerebral ischemia's effects and influencing stroke risk. This retrospective study examined collateral circulation, admission ischemic stroke status, and long-term recurrence in patients with multiple craniocervical artery stenoses. Consecutive symptomatic internal carotid artery (ICA) stenosis patients from the First Affiliated Hospital of Soochow University were recruited. Baseline data including medical histories and neurological function at admission were collected. Imaging techniques assessed collateral compensative capacity. Multivariate logistic regression analysis was used to investigate the association between collateral circulation and case status. A total of 559 patients with symptomatic ICA stenosis were included, among whom 153 (27.4%) had concurrent moderate to severe vertebro-basilar artery (VBA) stenosis. Dizziness, weakness/numbness, and slurring of speech were the primary symptoms in all patients. Over 36 months, 71 (12.7%) patients experienced a recurrence of acute ischemic stroke (AIS). In multivariate analysis, collateral circulation was found to be negatively associated with AIS (regional leptomeningeal collateral [rLMC] scores: OR: 0.798, 95% CI: 0.743-0.857, p < 0.001; Tan scores: OR: 0.478, 95% CI: 0.336-0.679, p < 0.001). Meanwhile, the collateral circulation scores were significantly associated with the recurrence of AIS within 3 years (rLMC scores: OR: 0.926, 95% CI: 0.860-0.997, p = 0.042; Tan scores: OR: 0.467, 95% CI: 0.306-0.712, p < 0.001). Most associations remained significant in the subgroup of patients with VBA stenosis. Favorable collateral circulation in multiple craniocervical artery stenosis patients reduced long-term ischemic event recurrence. Stratifying treatment risks is essential for optimizing outcomes.
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Estenose das Carótidas , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/etiologia , Constrição Patológica , Estudos Retrospectivos , Circulação Colateral , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , ArtériasRESUMO
Wavelength conversion based on hybrid inorganic-organic sensitized triplet-triplet annihilation upconversion (TTA-UC) is promising for applications such as photovoltaics, light-emitting-diodes, photocatalysis, additive manufacturing, and bioimaging. The efficiency of TTA-UC depends on the population of triplet excitons involved in triplet energy transfer (TET), the driving force in TET, and the coupling strength between the donor and acceptor. Consequently, achieving highly efficient TTA-UC necessitates the precise control of the electronic states of inorganic donors. However, conventional covalently bonded nanocrystals (NCs) face significant challenges in this regard. Herein, a novel strategy to exert control over electronic states is proposed, thereby enhancing TET and TTA-UC by incorporating ionic-bonded CsPbBr3 and lanthanide Ce3+ ions into composite NCs. These composite-NCs exhibit high photoluminescence quantum yield, extended single-exciton lifetime, quantum confinement, and uplifted energy levels. This engineering strategy of electronic states engendered a comprehensive impact, augmenting the population of triplet excitons participating in the TET process, enhancing coupling strength and the driving force, ultimately leading to an unconventional, dopant concentration-dependent nonlinear enhancement of UC efficiency. This work not only advances fundamental understanding of hybrid TTA-UC but also opens a door for the creation of other ionic-bonded composite NCs with tunable functionalities, promising innovations for next-generation optoelectronic applications.
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Background: The aim of this study was to investigate the safety and efficacy of computed tomography (CT)-guided hookwire localization and new CT-guided medical glue combined with methylene blue (MGMB) localization before video-assisted thoracoscopic surgery (VATS) for solitary pulmonary nodules (SPNs) and to analyze the risk factors for complications after localization. Methods: A total of 620 patients, comprising 727 SPNs, admitted to the Department of Thoracic Surgery of the First Hospital of the University of Science and Technology of China between December 2019 and July 2022 were retrospectively studied and case-control analyzed. According to the localization method, 620 patients were divided into the hookwire group (n=310) and MGMB group (n=310). The localization time, localization-to-surgery interval, operative time, length of hospitalization, and complication rate were compared between the 2 groups. Logistic regression was used to analyze the risk factors for the occurrence of complications in each group of localization methods. Results: Compared to the hookwire group, the MGMB group had a shorter localization time (8.59±3.69 vs. 7.35±2.99 min; P<0.001), shorter hospital stay (5.60±2.13 vs. 6.73±2.86 days; P<0.001), and shorter operative time (103.48±54.11 vs. 98.59±49.92 min; P=0.33). The preoperative localization success rate was 99.4% (355/357) and 100% (370/370) in the hookwire group and MGMB group, respectively. No death or serious complications occurred during the localization process, but the overall complication rate was lower in the MGMB group (69/310, 22.3%) than in the hookwire group (105/310, 33.9%) (P<0.001). Logistic regression analysis showed that age, number of nodules, and localization time were risk factors for total complications, while localization technique was a protective factor for total complications [odds ratio =0.590; 95% confidence interval (CI): 0.405-0.860; P<0.05]. Conclusions: Both techniques could effectively locate SPNs before VATS; however, MGMB localization was found to be associated with a lower complication rate, shorter localization time, better safety, and higher potential clinical value and is thus worthy of clinical promotion.
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BACKGROUND: The purpose of this research was to evaluate the safety and efficacy of a self-expandable metallic stent (SEMS) combined with iodine-125 (125I) seeds in the treatment of Bismuth type I or II malignant biliary obstruction (MBO). METHODS: The clinical data of 74 cases of MBO treated with percutaneous SEMS combined with 125I seeds (combination group) and 81 cases of MBO treated with SEMS implantation alone (control group) in our hospital from January 2015 to December 2019 were retrospectively analyzed. The short-term and long-term efficacy of the two groups were compared. Multivariate Cox regression analysis was used to analyze the factors affecting the surgical efficacy and survival rate. RESULTS: The liver blood test results of both groups improved at one week and one month post-stent insertion. No significant difference was established in the short-term efficacy or complications between the two groups (P = NS). Improved stent patency was observed in the combined group, 9.01 ± 4.38 months versus 6.79 ± 3.13 months, respectively (P < 0.001). Improved survival was also noted in the combined group 12.08 ± 5.38 months and 9.10 ± 4.16 months, respectively (P < 0.001). Univariate and multivariate analyses showed that the type of biliary stent and liver metastasis were independent factors affecting survival. CONCLUSION: The implementation of SEMS combined with 125I seeds resulted in significantly longer stent patency and survival times than that of SEMS implantation alone, which is thus worthy of clinical promotion and application.
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Colestase , Stents Metálicos Autoexpansíveis , Humanos , Bismuto , Colestase/etiologia , Colestase/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Stents Metálicos Autoexpansíveis/efeitos adversos , Stents/efeitos adversosRESUMO
Advances in imaging techniques have led to a rise in the diagnosis of spontaneous cervicocranial arterial dissection (SCCAD), which is now considered a common cause of stroke in young adults. However, our understanding of the pathophysiological mechanisms underlying SCCAD remains limited. Prior studies have proposed various factors contributing to arterial wall weakness or stress as potential causes for SCCAD. A combination of biopsies, case reports, and case-control studies suggests that inflammatory changes and autoimmunity may play roles in the cascade of events leading to SCCAD. In this review, we examine the close relationship between SCCAD, chronic inflammation, and autoimmune diseases, aiming to explore potential underlying pathophysiological mechanisms connecting these conditions. While some relevant hypotheses and studies exist, direct evidence on this topic is still relatively scarce. Further investigation of the underlying mechanisms in larger clinical cohorts is needed, and the exploration of animal models may provide novel insights.