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Effectively harnessing the assembly of achiral carbon dots into a chiral manner is a prominent step for applying carbon dots into the area of stereoselective optoelectronics and theranostics. Herein, magnetic-modulated and circularly polarized luminescence (CPL)-active photonic thin films were presented in this article via co-assembly and magnetic-mediation strategy of cellulose nanocrystals, carbon dots and magnetic nanoparticles. The photonic bandgap of the composite films is modulated via interfacial interactions between the building blocks, and more efficiently via external magnetic field which can further enhance the selective reflection of the films with a maximum CPL anisotropic factor as high as -0.92, indicating the optimized condition for achieving CPL signals is basically when the photonic bandgap (PBG) are close to the emission peaks of nanocomposite films, which may essentially facilitate the selective reflection effect and leads to the output of opposite CPL signals. Such strategy would inevitably boost the development of carbon dots based chiral devices and reagents into the realm of chirality-related biological issues and next generation chiral optoelectronics.
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INTRODUCTION: In December 2019, COVID-19 emerged in Wuhan, Hubei Province, China, and rapidly spread worldwide. On December 2022, the Chinese government ended the zero-COVID policy, leading to a surge in cases and significantly impacting daily life. IBD patients face heightened infection risks and substantial effects on their quality of life during the pandemic. METHODS: This cross-sectional study collected demographic, COVID-19-related, and HRQoL data from 224 IBD patients who had previously received treatment at Nanjing BenQ Medical Center. Participants completed an online survey between January 9, 2023, and January 23, 2023. The SIBDQ was used to assess HRQoL. Statistical analysis was performed using SPSS version 26. RESULTS: The study found that UC patients reported higher HRQoL compared to CD patients (p = 0.037). Patients who perceived themselves as less susceptible to COVID-19 had higher scores (p = 0.006 and p = 0.009). Those whose work or study was unaffected also had higher scores (p < 0.001 and p = 0.002). Additionally, irregular medication adherence was associated with lower HRQoL scores (p = 0.014 and p = 0.007). Multivariate linear regression results showed that IBD patients whose work or study was affected during the COVID-19 pandemic scored lower than those who were not affected (p = 0.038; 95% CI, -7.96 to -0.25). Patients who discontinued IBD medication scored higher than those with irregular medication use (p = 0.020; 95% CI, 1.00 to 10.90). CONCLUSIONS: This study highlights the significant impact of the COVID-19 pandemic on the HRQoL of IBD patients. The findings emphasize the need for integrated care addressing both the physical and psychological aspects of IBD.
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COVID-19 , Enfermedades Inflamatorias del Intestino , Calidad de Vida , Humanos , COVID-19/epidemiología , COVID-19/psicología , Masculino , Femenino , Estudios Transversales , China/epidemiología , Adulto , Persona de Mediana Edad , Enfermedades Inflamatorias del Intestino/psicología , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , SARS-CoV-2 , Cumplimiento de la Medicación/estadística & datos numéricos , Cumplimiento de la Medicación/psicología , Encuestas y Cuestionarios , Adulto Joven , Política de SaludRESUMEN
The pathogenesis of intestinal fibrosis in Crohn's disease (CD) remains unclear. Mer receptor tyrosine kinase (MerTK) is an immunosuppressive protein specifically expressed in macrophages. Osteopontin (OPN), also known as secreted phosphoprotein 1, contributes to inflammation and wound repair. This study investigates the potential profibrotic pathway in MerTK+ macrophages in order to provide a possible therapeutic target for intestinal fibrosis. MerTK expression in the inflamed and stenotic bowels was evaluated. The MerTK/ERK/TGF-ß1 pathway was overactivated in the fibrotic intestinal tissues of patients with CD. This pathway was induced by epithelial cell apoptosis, resulting in activated fibroblasts with increased TGF-ß1 secretion. OPN upregulated TGF production by altering ERK1/2 phosphorylation, as evidenced by OPN or MerTK knockdown and OPN overexpression in vitro. MerTK inhibitor UNC2025 alleviated intestinal fibrosis in mouse colitis models, suggesting a potential therapeutic target for intestinal fibrosis in patients with CD.
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Objectives: Prolonged intubation (PI) is a frequently encountered severe complication among patients following cardiac surgery (CS). Solely concentrating on preoperative data, devoid of sufficient consideration for the ongoing impact of surgical, anesthetic, and cardiopulmonary bypass procedures on subsequent respiratory system function, could potentially compromise the predictive accuracy of disease prognosis. In response to this challenge, we formulated and externally validated an intelligible prediction model tailored for CS patients, leveraging both preoperative information and early intensive care unit (ICU) data to facilitate early prophylaxis for PI. Methods: We conducted a retrospective cohort study, analyzing adult patients who underwent CS and utilizing data from two publicly available ICU databases, namely, the Medical Information Mart for Intensive Care and the eICU Collaborative Research Database. PI was defined as necessitating intubation for over 24â h. The predictive model was constructed using multivariable logistic regression. External validation of the model's predictive performance was conducted, and the findings were elucidated through visualization techniques. Results: The incidence rates of PI in the training, testing, and external validation cohorts were 11.8%, 12.1%, and 17.5%, respectively. We identified 11 predictive factors associated with PI following CS: plateau pressure [odds ratio (OR), 1.133; 95% confidence interval (CI), 1.111-1.157], lactate level (OR, 1.131; 95% CI, 1.067-1.2), Charlson Comorbidity Index (OR, 1.166; 95% CI, 1.115-1.219), Sequential Organ Failure Assessment score (OR, 1.096; 95% CI, 1.061-1.132), central venous pressure (OR, 1.052; 95% CI, 1.033-1.073), anion gap (OR, 1.075; 95% CI, 1.043-1.107), positive end-expiratory pressure (OR, 1.087; 95% CI, 1.047-1.129), vasopressor usage (OR, 1.521; 95% CI, 1.23-1.879), Visual Analog Scale score (OR, 0.928; 95% CI, 0.893-0.964), pH value (OR, 0.757; 95% CI, 0.629-0.913), and blood urea nitrogen level (OR, 1.011; 95% CI, 1.003-1.02). The model exhibited an area under the receiver operating characteristic curve (AUROC) of 0.853 (95% CI, 0.840-0.865) in the training cohort, 0.867 (95% CI, 0.853-0.882) in the testing cohort, and 0.704 (95% CI, 0.679-0.727) in the external validation cohort. Conclusions: Through multicenter internal and external validation, our model, which integrates early ICU data and preoperative information, exhibited outstanding discriminative capability. This integration allows for the accurate assessment of PI risk in the initial phases following CS, facilitating timely interventions to mitigate adverse outcomes.
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Gasdermins (GSDMs) serve as pivotal executors of pyroptosis and play crucial roles in host defence, cytokine secretion, innate immunity, and cancer. However, excessive or inappropriate GSDMs activation is invariably accompanied by exaggerated inflammation and results in tissue damage. In contrast, deficient or impaired activation of GSDMs often fails to promptly eliminate pathogens, leading to the increasing severity of infections. The activity of GSDMs requires meticulous regulation. The dynamic modulation of GSDMs involves many aspects, including autoinhibitory structures, proteolytic cleavage, lipid binding and membrane translocation (oligomerization and pre-pore formation), oligomerization (pore formation) and pore removal for membrane repair. As the most comprehensive and efficient regulatory pathway, posttranslational modifications (PTMs) are widely implicated in the regulation of these aspects. In this comprehensive review, we delve into the complex mechanisms through which a variety of proteases cleave GSDMs to enhance or hinder their function. Moreover, we summarize the intricate regulatory mechanisms of PTMs that govern GSDMs-induced pyroptosis.
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Gasderminas , Procesamiento Proteico-Postraduccional , Proteolisis , Endopeptidasas , Inmunidad Innata , Péptido HidrolasasRESUMEN
Hypervirulent Klebsiella pneumoniae (hvKP) is a highly lethal opportunistic pathogen that elicits more severe inflammatory responses compared to classical Klebsiella pneumoniae (cKP). In this study, we investigated the interaction between hvKP infection and the anti-inflammatory immune response gene 1 (IRG1)-itaconate axis. Firstly, we demonstrated the activation of the IRG1-itaconate axis induced by hvKP, with a dependency on SYK signaling rather than STING. Importantly, we discovered that exogenous supplementation of itaconate effectively inhibited excessive inflammation by directly inhibiting SYK kinase at the 593 site through alkylation. Furthermore, our study revealed that itaconate effectively suppressed the classical activation phenotype (M1 phenotype) and macrophage cell death induced by hvKP. In vivo experiments demonstrated that itaconate administration mitigated hvKP-induced disturbances in intestinal immunopathology and homeostasis, including the restoration of intestinal barrier integrity and alleviation of dysbiosis in the gut microbiota, ultimately preventing fatal injury. Overall, our study expands the current understanding of the IRG1-itaconate axis in hvKP infection, providing a promising foundation for the development of innovative therapeutic strategies utilizing itaconate for the treatment of hvKP infections.
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Infecciones por Klebsiella , Klebsiella pneumoniae , Humanos , Klebsiella pneumoniae/genética , Disbiosis/tratamiento farmacológico , Infecciones por Klebsiella/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Alquilación , Quinasa SykRESUMEN
Because the combination of chiral and magnetic properties is becoming more and more attractive for magneto-chiral phenomena, we here aim at exploring the induction of chirality to achiral magnetic molecules as a strategy for the preparation of magneto-chiral objects. To this end, we have associated free base- and metallo-porphyrins with silica nano helices, using a variety of elaboration methods, and have studied them mainly by electronic natural circular dichroism (NCD) and magnetic circular dichroism (MCD) spectroscopies. While electrostatic or covalent surface grafting uniformly yielded very low induced CD (ICD) for the four assayed porphyrins, a moderate response was observed when the porphyrins were incorporated into the interior of the double-walled helices, likely due to the association of the molecules with the chirally-organized gemini surfactant. A generally stronger, but more variable, ICD was observed when the molecules were drop casted onto the helices immobilised on a quartz plate, likely due to the different capacities of the porphyrins to aggregate into chiral assemblies. Electronic spectroscopy, electron microscopy and IR spectroscopy were used to interpret the patterns of aggregation and their influence on ICD and MCD. No enhancement of MCD was observed as a result of association with the nanohelices except in the case of the free base, 5,10,15,20-tetra-(4-sulfonatophenyl)porphyrin (TPPS). This nanocomposite demonstrated a large ICD in the Soret region and a large MCD in the Q-region due to J-aggregation. However, no induced MChD was observed, possibly due to the spectral mismatch between the ICD and MCD peaks.
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OBJECTIVES: We aimed to determine the current incidence rate and risk factors for surgical site infection (SSI) after abdominal surgery in China and to further demonstrate the clinical features of patients with SSI. BACKGROUND: Contemporary epidemiology and clinical features of SSI after abdominal surgery remain poorly characterized. METHODS: A prospective multicenter cohort study was conducted from March 2021 to February 2022; the study included patients who underwent abdominal surgery at 42 hospitals in China. Multivariable logistic regression analysis was performed to identify risk factors for SSI. Latent class analysis (LCA) was used to explore the population characteristics of SSI. RESULTS: In total, 23,982 patients were included in the study, of whom 1.8% developed SSI. There was a higher SSI incidence in open surgery (5.0%) than in laparoscopic or robotic surgeries (0.9%). Multivariable logistic regression indicated that the independent risk factors for SSI after abdominal surgery were older age, chronic liver disease, mechanical bowel preparation, oral antibiotic bowel preparation, colon or pancreas surgery, contaminated or dirty wounds, open surgery, and colostomy/ileostomy. LCA revealed 4 subphenotypes in patients undergoing abdominal surgery. Types α and ß were mild subclasses with a lower SSI incidence; whereas types γ and δ were the critical subgroups with a higher SSI incidence, but their clinical features were different. CONCLUSIONS: LCA identified 4 subphenotypes in patients who underwent abdominal surgery. Types γ and δ were critical subgroups with a higher SSI incidence. This phenotype classification can be used to predict SSI after abdominal surgery.
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Laparoscopía , Infección de la Herida Quirúrgica , Humanos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Estudios Prospectivos , Estudios de Cohortes , Laparoscopía/efectos adversos , Factores de Riesgo , IncidenciaRESUMEN
PURPOSES: Screw loosening is a common complication of iliosacral screw fixation, with subsequent loss of stability and fracture re-displacement. This study aimed to investigate the incidence of and risk factors for screw loosening after iliosacral screw fixation for posterior pelvic ring injury. METHODS: A total of 135 patients with posterior pelvic ring injuries who were treated with iliosacral screw fixation in our department between July 2015 and April 2021 were selected for this retrospective analysis. The possible risk factors for screw loosening were investigated using univariate and multivariate logistic regression analyses of patient demographics and trauma-related and iatrogenic variables, including age, sex, body mass index, Osteoporosis Self-Assessment Tool for Asians (OSTA) index, mechanism of injury, Young-Burgess classification, site of injury, type of injury, type of screw, mode of fixation, numbers of guidewire adjustments, accuracy of screw position, and quality of fracture reduction. RESULTS: The incidence of screw loosening was 15.6% (n = 21). The mean duration for screw loosening was 3.2 ± 1.5 months after operation. Univariate analysis results showed that the Young-Burgess classification, type of injury, site of injury, type of screw, mode of fixation, and OSTA index might be related to screw loosening (p < 0.05). According to the multivariate logistic regression, vertical shear injuries (Odds ratios [OR] 9.80, 95% Confidence intervals [CI] [1.96-73.28], p = 0.008), type of injury (OR 0.25, 95% CI [0.13-0.79], p = 0.027), common screws (OR 6.94, 95% CI [1.53-31.40], p = 0.012), screws insertion only at the level of the first sacral segment (S1) (OR 8.79, 95% CI [1.18-65.46], p = 0.034), injury site located in the medial sacral foramina (OR 6.28, 95% CI [1.16-34.06], p = 0.033), and lower OSTA index [OR 0.41, 95% CI [0.24-0.71], p = 0.001] were significantly related to screw loosening. CONCLUSIONS: Vertical shear injuries, sacral fractures, injury site located in the medial sacral foramina, and lower OSTA index are significantly associated with the postoperative occurrence of screw loosening. Transiliac-transsacral screw fixation and screws insertion both at the level of the S1 and second sacral segment can prevent screw loosening.
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Fracturas Óseas , Huesos Pélvicos , Humanos , Huesos Pélvicos/cirugía , Huesos Pélvicos/lesiones , Fijación Interna de Fracturas/efectos adversos , Fijación Interna de Fracturas/métodos , Incidencia , Estudios Retrospectivos , Tornillos Óseos/efectos adversos , Fracturas Óseas/cirugía , Sacro/cirugía , Sacro/lesiones , Factores de Riesgo , Ilion/cirugíaRESUMEN
Background: The great heterogeneity of patients with chronic critical illness (CCI) leads to difficulty for intensive care unit (ICU) management. Identifying subphenotypes could assist in individualized care, which has not yet been explored. In this study, we aim to identify the subphenotypes of patients with CCI and reveal the heterogeneous treatment effect of fluid balance for them. Methods: In this retrospective study, we defined CCI as an ICU length of stay over 14 days and coexists with persistent organ dysfunction (cardiovascular Sequential Organ Failure Assessment (SOFA) score ≥1 or score in any other organ system ≥2) at Day 14. Data from five electronic healthcare record datasets covering geographically distinct populations (the US, Europe, and China) were studied. These five datasets include (1) subset of Derivation (MIMIC-IV v1.0, US) cohort (2008-2019); (2) subset Derivation (MIMIC-III v1.4 'CareVue', US) cohort (2001-2008); (3) Validation I (eICU-CRD, US) cohort (2014-2015); (4) Validation II (AmsterdamUMCdb/AUMC, Euro) cohort (2003-2016); (5) Validation III (Jinling, CN) cohort (2017-2021). Patients who meet the criteria of CCI in their first ICU admission period were included in this study. Patients with age over 89 or under 18 years old were excluded. Three unsupervised clustering algorithms were employed independently for phenotypes derivation and validation. Extreme Gradient Boosting (XGBoost) was used for phenotype classifier construction. A parametric G-formula model was applied to estimate the cumulative risk under different daily fluid management strategies in different subphenotypes of ICU mortality. Findings: We identified four subphenotypes as Phenotype A, B, C, and D in a total of 8145 patients from three countries. Phenotype A is the mildest and youngest subgroup; Phenotype B is the most common group, of whom patients showed the oldest age, significant acid-base abnormality, and low white blood cell count; Patients with Phenotype C have hypernatremia, hyperchloremia, and hypercatabolic status; and in Phenotype D, patients accompany with the most severe multiple organ failure. An easy-to-use classifier showed good effectiveness. Phenotype characteristics showed robustness across all cohorts. The beneficial fluid balance threshold intervals of subphenotypes were different. Interpretation: We identified four novel phenotypes that revealed the different patterns and significant heterogeneous treatment effects of fluid therapy within patients with CCI. A prospective study is needed to validate our findings, which could inform clinical practice and guide future research on individualized care. Funding: This study was funded by 333 High Level Talents Training Project of Jiangsu Province (BRA2019011), General Program of Medical Research from the Jiangsu Commission of Health (M2020052), and Key Research and Development Program of Jiangsu Province (BE2022823).
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Helical perovskite nanocrystals (H-PNCs) were prepared using nanometric silica helical ribbons as platforms for the in situ growth of the crystals using the supersaturated recrystallization method. The H-PNCs grow inside nanometric helical porous silica, and their handedness is determined by the handedness of porous silica templates. They show both strong induced circular dichroism (CD) and strong induced circularly polarized luminescence (CPL) signals, with high dissymmetry g-factors. Right-handed and left-handed PNCs show respectively positive and negative CD and CPL signals, with a dissymmetry g-factor (abs and lum) of â¼±2 × 10-2. Simulations based on the boundary element method demonstrate that the circular dichroism originates from the chiral shape of H-PNCs.
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The synthesis and characterization of diketopyrrolopyrroles and perylenemonoimidodiesters linked to a substituted benzoic acid in the ortho, meta, and para positions, are reported. Grafting of these dyes on the surface of chiral silica nanohelices is used to probe how the morphology of the platform at the mesoscopic level affects the induction of chiroptical properties onto achiral molecular chromophores. The grafted structures are weakly (diketopyrrolopyrroles) or strongly (perylenemonoimidodiesters) emissive, exhibiting both locally-excited state emission and a broad, structureless emission assigned to excimers. The dissymmetry factors obtained using circular dichroism highlight optimized supramolecular organization between the chromophores for enhancing the chiroptical properties of the system. In the ortho- derivatives, poor organization due to steric hindrance is reflected in a low density of chromophores on walls of the silica-nanostructures (<0.1 vs. >0.3 and up to 0.6â molecules/nm2 for the ortho and meta or para derivatives, respectively) and lower gabs values than in the other derivatives (gabs <2×10-5 vs 6×10-5 for the ortho and para derivatives, respectively). The para derivatives presented a better organization and increased values of gabs . All grafted chromophores evidence varying degrees of excimer emission which was not found to directly correlate to their grafting density.
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Metabolism could be served as a guiding force for immunity, and macrophages undergo drastic metabolic reprogramming during inflammatory processes, including enhancing glycolysis and reshaping the tricarboxylic acid cycle (TCA) cycle. The disrupted TCA cycle facilitates itaconate accumulation, consistent with the significant up-regulation of immune response gene 1 (IRG1) in activated macrophages. IRG1 catalyzes the decarboxylation of cis-aconitate to synthesize itaconate, and notably, the IRG1-Itaconate axis has excellent potential to link macrophages' immunity and metabolism. Here, we review vital molecules that affect the activation of the IRG1-Itaconate axis, including interferon regulatory factor 1/9 (IRF1/9), transcription 1 and 3 (STAT1/3), CCAAT enhancer-binding protein ß (C/EBPß), and the protein kinase C (PKC). We then focus on how the IRG1-Itaconate axis regulates the inflammatory pathway in macrophages, proposed to involve kelch-like ECH-associated protein 1 (Keap1), NOD-, LRR- and pyrin domain-containing 3 (NLRP3), gasdermin D (GSDMD), activating transcription factor 3 (ATF3), receptor-interacting protein kinase-3 (RIPK3), et al. In addition, we provide an overview of the way the axis participates in the metabolism of macrophages. Eventually, we summarize current connections between the IRG1-Itaconate axis and inflammatory diseases, bringing light to new therapeutic opportunities in inflammatory diseases.
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Factor 2 Relacionado con NF-E2 , Succinatos , Humanos , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Succinatos/metabolismo , MacrófagosRESUMEN
INTRODUCTION: Intestinal fibrosis is a common complication of Inflammatory Bowel Disease (IBD) with no available drugs. The current therapeutic principle is surgical intervention as the core. Intestinal macrophages contribute to both the progression of inflammation and fibrosis. Understanding the role of macrophages in the intestinal microenvironment could bring new hope for fibrosis prevention or even reversal. AREAS COVERED: This article reviewed the most relevant reports on macrophage in the field of intestinal fibrosis. The authors discussed current opinions about how intestinal macrophages function and interact with surrounding mediators during inflammation resolution and fibrostenotic IBD. Based on biological mechanisms findings, authors summarized related clinical trial outcomes. EXPERT OPINION: The plasticity of intestinal macrophages allows them to undergo dramatic alterations in their phenotypes or functions when exposed to gastrointestinal environmental stimuli. They exhibit distinct metabolic characteristics, secrete various cytokines, express unique surface markers, and transmit different signals. Nevertheless, the specific mechanism through which the intestinal macrophages contribute to intestinal fibrosis remains unclear. It should further elucidate a novel therapeutic approach by targeting macrophages, especially distinct mechanisms in specific subgroups of macrophages involved in the progression of fibrogenesis in IBD.
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Enfermedades Inflamatorias del Intestino , Humanos , Enfermedades Inflamatorias del Intestino/terapia , Macrófagos/metabolismo , Inflamación , Citocinas/metabolismo , FibrosisRESUMEN
The discovery of STING-related innate immunity has recently provided a deep mechanistic understanding of immunopathy. While the detrimental effects of STING during sepsis had been well documented, the exact mechanism by which STING causes lethal sepsis remains obscure. Through single-cell RNA sequence, genetic approaches, and mass spectrometry, we demonstrate that STING promotes sepsis-induced multiple organ injury by inducing macrophage ferroptosis in a cGAS- and interferon-independent manner. Mechanistically, Q237, E316, and S322 in the CBD domain of STING are critical binding sites for the interaction with the coiled-coil domain of NCOA4. Their interaction not only triggers ferritinophagy-mediated ferroptosis, but also maintains the stability of STING dimers leading to enhanced inflammatory response, and reduces the nuclear localization of NCOA4, which impairs the transcription factor coregulator function of NCOA4. Meanwhile, we identified HET0016 by high throughput screening, a selective 20-HETE synthase inhibitor, decreased STING-induced ferroptosis in peripheral blood mononuclear cells from patients with sepsis and mortality in septic mice model. Our findings uncover a novel mechanism by which the interaction between STING and NCOA4 regulates innate immune response and ferroptosis, which can be reversed by HET0016, providing mechanistic and promising targets insights into sepsis.
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Ferroptosis , Proteínas de la Membrana/metabolismo , Sepsis , Animales , Inmunidad Innata/genética , Leucocitos Mononucleares/metabolismo , Macrófagos/metabolismo , Proteínas de la Membrana/genética , Ratones , Coactivadores de Receptor Nuclear/metabolismo , Sepsis/genética , Factores de Transcripción/metabolismoRESUMEN
Background: Traditional percutaneous catheter drainage (PCD) and surgical intervention could not always achieve satisfactory results for patients with Crohn's disease (CD) who have complications with intra-abdominal abscess. We proposed a trocar puncture with sump drainage for the treatment of CD with intra-abdominal abscess and compared it with the conventional PCD and surgical intervention. Methods: Crohn's disease patients with intra-abdominal abscess and admitted to our hospital from 2011 to 2020 were identified by reviewing the electronic medical records. We divided them into Trocar, PCD, and fecal diverting (FD) groups, according to the ways of treating an abscess. Outcomes, risk factors for abscess recurrence, and postoperative complications were compared among the three groups. Results: A total of 69 patients were included and they were divided into Trocar (n = 18), PCD (n = 29), and FD (n = 22) groups. Four patients in the PCD group were transferred to receive the FD surgery due to the failure of initial treatment. The incidence of abscess recurrence was significantly higher in the PCD (48%) and FD (50%) groups compared to the patients using the trocar puncture with the sump drain (Trocar group) (16.7%). There were 8 patients in Trocar, 22 in PCD, and 20 s in the FD group who received enterectomy. None of the patients in the Trocar had an ultimate stoma and the incidence of postoperative complications was statistically lower [0% (Trocar) vs. 31.8% (PCD) vs. 45% (FD), P < 0.05]. The way of initial treating of the abscess was significantly correlated with the abscess recurrence and postoperative complications. Conclusions: Trocar puncture with a sump drain had a lower incidence of abscess recurrence, abdominal adhesions, postdrainage, and postoperative complications compared to the conventional PCD or surgical intervention.
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BACKGROUND: Stimulator of interferon genes (STING) has essential functions in the immune responses and can induce cancer cell apoptosis. However, it is not completely clear how STING plays a role in colitis-associated colorectal cancer (CAC) and whether it can trigger pyroptosis during the tumorigenesis of CAC. METHODS: To investigate the role of STING-modulated pyroptosis in the development of CAC, STING knockout and Wild type mice were challenged with azoxymethane (AOM) and dextran sodium sulfate (DSS) to establish a murine CAC model. STING pharmacological agonist was used to further study the functions of STING signaling in the tumorigenesis. Moreover, STING endogenous ligand was employed to verify the effects of STING in human colon cancer cells. RESULTS: STING deficiency mice were more susceptible to CAC by reducing pyroptosis of tumor cells, whereas overactivation of STING with the agonist suppressed tumorigenesis of CAC. STING also managed CAC development by modulating tumor cells proliferation, adhesion, and invasion, as well as inflammatory response. The ex vivo studies indicated that STING could induce pyroptosis via spleen tyrosine kinase (Syk), and Syk knockdown weakened such pyroptotic tumor cells death. In addition, the visible physical interaction between STING and Syk was observed in colorectal tumor samples of CAC patients. CONCLUSIONS: STING-mediated Syk signaling may regulate the tumorigenesis of CAC by modulating pyroptosis of tumor cells, and modulation of STING/Syk serves as a novel therapeutic strategy for CAC therapy.
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Neoplasias Asociadas a Colitis , Colitis , Neoplasias Colorrectales , Animales , Azoximetano/toxicidad , Carcinogénesis/patología , Colitis/inducido químicamente , Colitis/complicaciones , Neoplasias Colorrectales/metabolismo , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Humanos , Mucosa Intestinal/patología , Ratones , Ratones Endogámicos C57BL , Piroptosis , Quinasa Syk/metabolismoRESUMEN
Spleen tyrosine kinase (Syk) is a cytoplasmic non-receptor protein tyrosine kinase expressed in a variety of cells and play crucial roles in signal transduction. Syk mediates downstream signaling by recruiting to the dually phosphorylated immunoreceptor tyrosine-based activation motifs (ITAMs) of the transmembrane adaptor molecule or the receptor chain itself. In gut diseases, Syk is observed to be expressed in intestinal epithelial cells, monocytes/macrophages, dendritic cells and mast cells. Activation of Syk in these cells can modulate intestinal mucosal immune response by promoting inflammatory cytokines and chemokines production, thus regulating gut homeostasis. Due to the restriction of specificity and selectivity for the development of Syk inhibitors, only a few such inhibitors are available in gut diseases, including intestinal ischemia/reperfusion damage, infectious disease, inflammatory bowel disease, etc. The promising outcomes of Syk inhibitors from both preclinical and clinical studies have shown to attenuate the progression of gut diseases thereby indicating a great potential in the development of Syk targeted therapy for treatment of gut diseases. This review depicts the characterization of Syk, summarizes the signal pathways of Syk, and discusses its potential targeted therapy for gut diseases.
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Enfermedades del Sistema Digestivo/inmunología , Inmunidad Mucosa , Quinasa Syk/metabolismo , Quimiocinas , Citocinas/metabolismo , HumanosRESUMEN
Helical and twisted silica nanoribbons, deposited in an in-plane direction and with a random orientation, on a quartz substrate showed chiral optical scattering, and the helical nanoribbons had a g-factor of the order of 10-2 below 250 nm. Their signs depend on the handedness of the nanohelices. The effect of the morphology and the orientation of the helices on the chiral optical scattering were investigated with simulations via the boundary element method.