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1.
Cardiovasc Diabetol ; 23(1): 137, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664780

RESUMEN

BACKGROUND: The Triglyceride Glucose-Body Mass Index (TyG-BMI) has been established as a robust indicator of insulin resistance (IR), reflecting metabolic health across various populations. In general, lower TyG-BMI values are often associated with better metabolic health outcomes and a reduced risk of adverse health events in non-critically ill populations. Previous studies have highlighted a significant negative association between TyG-BMI and all-cause mortality (ACM) among critically ill atrial fibrillation patients. Given the high prevalence and severe outcomes associated with stroke, understanding how TyG-BMI at the time of ICU admission correlates with ACM in critically ill stroke patients becomes imperative. This study aims to assess the correlation between TyG-BMI and ACM in this specific patient cohort, exploring how traditional associations between TyG-BMI and metabolic health may differ in the context of acute, life-threatening illness. METHODS: Patient data were retrieved by accessing the Medical Information Mart for Intensive Care IV (MIMIC-IV 2.2) database, categorizing patients into three groups on the basis of TyG-BMI tertiles. The study evaluated both primary and secondary outcomes: the primary outcomes included the 90-day, 180-day, and 1-year ACM, while secondary outcomes encompassed ICU, in-hospital, and 30-day ACM. Our study employed the Kaplan-Meier (K-M) curve method for outcome comparison across the groups while utilizing multivariate Cox proportional-hazards regression models and restricted cubic splines (RCS) to explore TyG-BMI association with these outcomes. Additionally, interaction and subgroup analyses were performed, focusing on different mortality time points. RESULTS: Among a cohort of 1707 individuals diagnosed with stroke, the average age was 68 years (interquartile range [IQR]: 58-78 years), with 946 (55.42%) of the participants being male. The analysis of K-M curves suggested that patients having a lower TyG-BMI level faced a heightened risk of long-term ACM, whereas the short-term ACM exhibited no statistically significant differences across the three TyG-BMI groups. Furthermore, Cox proportional-hazards regression analysis validated a statistically significant increased risk of long-term ACM among patients belonging to the lowest TyG-BMI tertile. Additionally, RCS analysis results demonstrated L-shaped correlations between the TyG-BMI index and both short- and long-term ACM. These findings underscore the TyG-BMI predictive value for long-term mortality in stroke patients, highlighting a nuanced relationship that varies over different time frames. The results revealed no interactions between TyG-BMI and the stratified variables, with the exception of age. CONCLUSION: In our study, lower TyG-BMI levels in critically ill stroke patients are significantly related to a higher risk of long-term ACM within the context of the United States. This finding suggests the potential of TyG-BMI as a marker for stratifying long-term risk in this patient population. However, it's crucial to note that this association was not observed for short-term ACM, indicating that the utility of TyG-BMI may be more pronounced in long-term outcome prediction. Additionally, our conclusion that TyG-BMI could serve as a reliable indicator for managing and stratifying stroke patients over the long term is preliminary. To confirm our findings and assess the universal applicability of TyG-BMI as a prognostic tool, it is crucial to conduct rigorously designed research across various populations.


Asunto(s)
Biomarcadores , Glucemia , Índice de Masa Corporal , Enfermedad Crítica , Bases de Datos Factuales , Unidades de Cuidados Intensivos , Accidente Cerebrovascular , Triglicéridos , Humanos , Masculino , Anciano , Femenino , Glucemia/metabolismo , Factores de Tiempo , Persona de Mediana Edad , Medición de Riesgo , Triglicéridos/sangre , Factores de Riesgo , Biomarcadores/sangre , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/diagnóstico , Pronóstico , Enfermedad Crítica/mortalidad , Estudios Retrospectivos , Anciano de 80 o más Años , Resistencia a la Insulina , Estados Unidos/epidemiología
2.
Cardiovasc Diabetol ; 23(1): 100, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38500198

RESUMEN

BACKGROUND: Hemorrhagic stroke (HS), including non-traumatic intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH), constitutes a substantial proportion of cerebrovascular incidents, accounting for around 30% of stroke cases. The triglyceride-glucose index (TyG-i) represents a precise insulin resistance (IR) indicator, a crucial metabolic disturbance. Existing literature has demonstrated an association between TyG-i and all-cause mortality (ACM) among individuals suffering from ischemic stroke (IS). Yet, the TyG-i prognostic implications for severe HS patients necessitating intensive care unit (ICU) admission are not clearly understood. Considering the notably elevated mortality and morbidity associated with HS relative to IS, investigating this association is warranted. Our primary aim was to investigate TyG-i and ACM association among critically ill HS patients within an ICU context. METHODS: Herein, patients with severe HS were identified by accessing the Medical Information Mart for Intensive Care-IV (MIMIC-IV, version 2.2) database, using the International Classification of Diseases (ICD)-9/10 as diagnostic guidelines. Subsequently, we stratified the subjects into quartiles, relying on their TyG-i scores. Moreover, we measured mortality at ICU, in-hospital, 30 days, 90 days, and 1 year as the outcomes. Cox proportional hazards regression analysis and restricted cubic splines (RCS) were deployed for elucidating the relation between the TyG-i and ACM while utilizing the Kaplan-Meier (K-M) method to estimate survival curves. The findings' robustness was assessed by conducting subgroup analysis and interaction tests employing likelihood ratio tests. RESULTS: The analysis included 1475 patients, with a male predominance of 54.4%. Observed mortality rates in the ICU, hospital, 30 days, 90 days, and 1 year were 7.3%, 10.9%, 13.8%, 19.7%, and 27.3%, respectively. Multivariate Cox regression analysis results manifested that heightened TyG-i was significantly related to ACM at 30 days (adjusted hazard ratio [aHR]: 1.32; 95% confidence interval [CI]: 1.05-1.67; P = 0.020), 90 days (aHR: 1.27; 95% CI: 1.04-1.55; P = 0.019), and 1 year (aHR: 1.22; 95% CI: 1.03-1.44; P = 0.023). The results of RCS analysis demonstrated a progressive elevation in ACM risk with rising TyG-i levels. Interaction tests found no significant effect modification in this relationship. CONCLUSION: In summary, TyG-i exhibits a significant correlation with ACM among patients enduring critical illness due to HS. This correlation underscores the probable utility of TyG-i as a prognostic tool for stratifying HS patients according to their risk of mortality. Applying TyG-i in clinical settings could enhance therapeutic decision-making and the management of disease trajectories. Additionally, this investigation augments existing research on the linkage between the TyG-i and IS, elucidating the TyG-i's role in predicting mortality across diverse stroke categories.


Asunto(s)
Accidente Cerebrovascular Hemorrágico , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Masculino , Femenino , Enfermedad Crítica , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico , Glucosa , Triglicéridos , Glucemia , Factores de Riesgo , Biomarcadores
3.
Angew Chem Int Ed Engl ; 63(11): e202318799, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38230819

RESUMEN

Activation of stimulator of interferon genes (STING) by cyclic dinucleotides (CDNs) has been considered as a powerful immunotherapy strategy. While promising, the clinical translation of CDNs is still overwhelmed by its limited biostability and the resulting systemic immunotoxicity. Being differentiating from current application of exogenous CDNs to address these challenges, we herein developed one perylene STING agonist PDIC-NS, which not only promotes the production of endogenous CDNs but also inhibits its hydrolysis. More significantly, PDIC-NS can well reach lung-selective enrichment, and thus mitigates the systemic immunotoxicity upon intravenous administration. As a result, PDIC-NS had realized remarkable in vivo antitumor activity, and backward verified on STING knock out mice. Overall, this study states that PDIC-NS can function as three-in-one small-molecule STING agonist characterized by promoting the content and biostability of endogenous CDNs as well as possessing good tissue specificity, and hence presents an innovative strategy and platform for tumor chemo-immunotherapy.


Asunto(s)
Neoplasias , Perileno , Animales , Ratones , Nucleótidos Cíclicos , Inmunoterapia/métodos , Proteínas de la Membrana/genética , Neoplasias/tratamiento farmacológico
4.
Angew Chem Int Ed Engl ; 62(11): e202214586, 2023 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-36597125

RESUMEN

Reactive oxygen species (ROS) can act as cytotoxic radicals to directly kill tumor cells and concurrently trigger immunogenic cell death (ICD) to efficiently achieve tumor therapy. Thus motivated, we herein present one perylene monoamide-based ROS supergenerator (PMIC-NC) that not only induces hypoxia-enhanced Type-I ROS burst aided by proton transients but also triggers Type-I/II ROS production by electron or energy transfer under near-infrared (NIR) light irradiation and also elicits a strong ICD effect. More interesting, the mitochondria- and lung-specific distribution of PMIC-NC also boosts the tumor therapeutic efficiency. As a result, PMIC-NC was employed for NIR-triggered photodynamic therapy, hypoxia-enhanced chemotherapy and also displayed robust immunogenicity for systemic tumor eradication. This work thus contributes one proof-of-concept demonstration of perylene as an integrated therapeutic platform for efficient immunogenic photochemotherapy against hypoxic tumors.


Asunto(s)
Nanopartículas , Neoplasias , Perileno , Fotoquimioterapia , Humanos , Especies Reactivas de Oxígeno/metabolismo , Perileno/farmacología , Perileno/uso terapéutico , Rayos Infrarrojos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Hipoxia/tratamiento farmacológico , Línea Celular Tumoral , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Nanopartículas/uso terapéutico , Oxígeno/uso terapéutico
5.
Small ; 18(4): e2104521, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34821029

RESUMEN

High-performance photothermal theranostics is urgently desired for cancer therapy because of their good controllability and noninvasive features. The relatively low photothermal conversion efficiency is still at the drawbacks because of the absence of efficient extraneous carriers. Herein, a carrier-free nanomedicine is developed to in vivo self-deliver organic photothermal agents for efficient cancer phototheranostics. By a facile self-assembly strategy, the near-infrared (NIR)-absorbing conjugated oligomer IDIC-4F is fabricated into a carrier-free nanoparticle (DCF-P), showing ultrasmall size of nearly 4.0 nm with a nearly 100% of drug loading capacity. Notably, DCF-P achieves a superhigh photothermal conversion efficiency of 80.5% that is far greater than that of IDIC-4F-loaded nanomicelle DCF-M (57.3%). With the guidance of NIR fluorescence and photoacoustic dual-imaging, it is verified that DCF-P could well achieve tumor-preferential accumulation and retention at 4 h postinjection, and meanwhile shows highly efficient in vivo tumor elimination with good biosafety. This study thus contributes a novel concept for designing ultrasmall nanoparticle characteristics of preferential accumulation in tumors, and also provides a strategy for creating high-performance carrier-free nanomedicine via highly ordered molecular stacking.


Asunto(s)
Neoplasias , Técnicas Fotoacústicas , Nanomedicina Teranóstica , Portadores de Fármacos/química , Humanos , Nanopartículas , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Técnicas Fotoacústicas/métodos , Fototerapia/métodos , Medicina de Precisión , Nanomedicina Teranóstica/métodos
6.
Environ Res ; 212(Pt A): 113155, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35351455

RESUMEN

BACKGROUND: Air pollution may be a contributing risk factor for obstructive sleep apnea (OSA). However, the health effects of co-exposure to multiple air pollutants on OSA patients remain unclear. OBJECTIVES: To assess the joint effect of multi-pollutant on sleep disordered breathing (SDB) parameters in patients with or without OSA and identify the dominant pollutants. METHODS: A total of 2524 outpatients from April 2020 to May 2021 were recruited in this cross-sectional study. Ambient air pollutant data were obtained from the nearest central monitoring stations to participants' residential address. SDB parameters were measured by the ApneaLink devices, including apnea-hypopnea index (AHI), hypopnea index (HI), oxygen desaturation index (ODI), average oxygen saturation (SpO2), percentage sleep time with <90% saturation (T90), and desaturation. Bayesian kernel machine regression (BKMR) was applied to evaluate the effects of multiple pollutants. RESULTS: Significant associations were observed between air pollutants and SDB parameters (including increases in AHI, HI, ODI, and desaturation) among patients with OSA. Co-exposure to air pollutants was positively correlated with AHI, HI, and ODI. PM10 and O3 dominated the effects of pollutant mixtures on OSA, with the highest posterior inclusion probability (PIP) values of 0.592 and 0.640, respectively. Stratified analysis showed that, compared to male patients with OSA, stronger effects on the SDB parameters were observed in female patients. Stronger associations were also found in the warm season than those in the cold season. CONCLUSION: Co-exposure to air pollutants was associated with SDB parameters among patients with OSA, PM10 and O3 might play the dominant roles.


Asunto(s)
Contaminantes Atmosféricos , Síndromes de la Apnea del Sueño , Apnea Obstructiva del Sueño , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Teorema de Bayes , Estudios Transversales , Femenino , Humanos , Masculino , Oxígeno , Síndromes de la Apnea del Sueño/complicaciones , Síndromes de la Apnea del Sueño/etiología , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/etiología
7.
Sleep Breath ; 26(1): 497-503, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34013438

RESUMEN

PURPOSE: To investigate the proportion and clinical characteristics of obstructive sleep apnea (OSA) in Chinese patients with polycystic ovarian syndrome (PCOS) through home sleep apnea test (HSAT) and to evaluate the reproductive endocrine and metabolic characteristics in these patients. METHODS: The study was a cross-sectional analysis of infertile PCOS patients who underwent sleep respiratory monitoring between January and December 2019 at Peking University Third Hospital Reproductive Medical Center and respiratory and critical care medicine department. The prevalence of OSA, body mass index (BMI), menstruation, reproductive endocrine, and metabolic characteristics were collected in patients with PCOS. Logistic regression was performed to identify significant relationships among these factors and OSA. RESULTS: Amont 328 patients with PCOS, the prevalence of OSA was 40% (131/328), and six cases (5%) were severe. Univariate analysis showed that BMI and blood pressure were significantly higher in patients with OSA than in those without OSA (P < 0.05), whereas the anti-Mullerian hormone was lower than that in patients without OSA. In terms of glucose and lipid metabolism, the glycosylated hemoglobin (HbA1c), fasting plasma glucose, and fasting insulin levels were significantly higher in patients with PCOS and comorbid OSA than in those without OSA (all P < 0.05). Patients with OSA also had higher triglyceride, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein levels and lower high-density lipoprotein cholesterol levels (P < 0.05). Logistic regression analysis revealed that higher BMI, elevated serum testosterone, and decreased high-density lipoprotein cholesterol (HDL-C) are correlated with occurrence of OSA (P < 0.05). CONCLUSION: OSA in patients with PCOS was associated with multiple alterations in indexes of reproductive endocrine and metabolic disorders.


Asunto(s)
Síndrome del Ovario Poliquístico/complicaciones , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/epidemiología , Adulto , China , Estudios Transversales , Glándulas Endocrinas/fisiopatología , Femenino , Humanos , Síndrome del Ovario Poliquístico/metabolismo , Síndrome del Ovario Poliquístico/fisiopatología
8.
Water Sci Technol ; 86(10): 2701-2717, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36450681

RESUMEN

A carbon derivative with Fe-Cu bimetallic organic framework (Fe-Cu-MOF@C) was prepared by microwave synthesis and pyrolysis. Using potassium persulfate (PS) as oxidant and 2,4-dichlorophenol (2,4-DCP) as target pollutant, the optimal preparation conditions of Fe-Cu-MOF@C were studied. The factors affecting the synthesis of Fe-Cu-MOF include microwave power, microwave time, microwave temperature, the molar ratio of metal ions to organic ligands, the molar ratio of iron and copper, etc. In addition, the influence of pyrolysis temperature on the performance of Fe-Cu-MOF@C cannot be ignored. The results show that Fe-Cu-MOF@C has the best catalytic performance when the microwave time is 30 min, the microwave power is 600 W, the microwave temperature is 150 °C, the molar ratio of (Fe2+ + Cu2+)/H2BDC is 10:3, the molar ratio of Fe2+/Cu2+ is 10:1, and the pyrolysis temperature is 700 °C. After 90 min of reaction, 2,4-DCP was completely removed. Repeatable experiments show that Fe-Cu-MOF@C has good stability and its service life can be restored by heat treatment. In this study, a heterogeneous catalyst with strong catalytic capacity, high stability and easy recovery was prepared by a simple and efficient process, which is conducive to the development of advanced oxidation technology and the progress of water environmental protection.


Asunto(s)
Microondas , Pirólisis , Catálisis , Carbono , Cobre
9.
Angew Chem Int Ed Engl ; 60(29): 16215-16223, 2021 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-33971079

RESUMEN

The systemic use of pharmaceutical drugs for cancer patients is a compromise between desirable therapy and side effects because of the intrinsic shortage of organ-specific pharmaceutical drug. Design and construction of pharmaceutical drug to achieve the organ-specific delivery is thus desperately desirable. We herein regulate perylene skeleton to effect organ-specificity and present an example of lung-specific distribution on the basis of bay-twisted PDIC-NC. We further demonstrate that PDIC-NC can target into mitochondria to act as cellular respiration inhibitor, inducing insufficient production of adenosine triphosphate, promoting endogenous H2 O2 and . OH burst, elevating calcium overload, efficiently triggering the synergistic apoptosis, autophagy and endoplasmic reticulum stress of lung cancer cells. The antitumor performance of PDIC-NC is verified on in vivo xenografted, metastasis and orthotopic lung cancer, presenting overwhelming evidences for potentially clinical application. This study contributes a proof-of-concept demonstration of twisted perylene to well attain lung-specific distribution, and meanwhile achieves intensive lung cancer chemotherapy.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Perileno/química , Perileno/farmacología , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Estrés del Retículo Endoplásmico/efectos de los fármacos , Humanos , Relación Estructura-Actividad
10.
J Org Chem ; 85(6): 4058-4066, 2020 03 20.
Artículo en Inglés | MEDLINE | ID: mdl-31994881

RESUMEN

A direct strategy for the selective synthesis of 3-acyl-1,2,4-oxadiazoles from alkynes and nitriles has been developed under iron(III) nitrate-mediated conditions. The mechanism includes three sequential procedures: iron(III) nitrate-mediated nitration of alkynes leads to α-nitroketones, dehydration of α-nitroketones provides the nitrile oxides, and 1,3-dipolar cycloaddition of nitrile oxides with nitriles produces 3-acyl-1,2,4-oxadiazoles under iron-mediated conditions. Iron(III) nitrate plays dual roles in the nitration of alkynes and the activation of nitriles, while the formation of pyrimidine/isoxazole byproducts can be efficiently inhibited.

11.
Sleep Breath ; 24(2): 745-750, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31853835

RESUMEN

PURPOSE: We sought to unravel the role of hydrogen sulfide (H2S) in the development of hypertension in patients with obstructive sleep apnea (OSA). METHODS: The study sample included 80 patients with OSA and 45 healthy controls. All subjects underwent measurement of blood pressure (BP) and serum H2S level in the morning. Twentynine of the 39 patients with OSA and concomitant hypertension and 23 of the 41 patients with OSA but no concomitant hypertension received continuous positive alveolar pressure (CPAP) therapy for 4 weeks. Twenty-four-hour ambulatory BP and serum H2S were determined before and after CPAP. Respiratory indices including apnea hypopnea index (AHI), lowest oxygen saturation (SaO2), and length of time < 90% saturated (T90) were determined by polysomnography. RESULTS: Associations between H2S, BP, respiratory indices, and changes with CPAP were analyzed. OSA patients had significantly higher systolic BP (p = 0.003) and diastolic BP (p = 0.009) and lower H2S levels (p = 0.02) compared to healthy controls. H2S negatively correlated with AHI (p = 0.005), T90 (p = 0.009), morning systolic BP (p = 0.02), and morning diastolic BP (p = 0.03). All respiratory indices were significantly improved (p < 0.05) after CPAP in OSA patients with or without hypertension. BP was significantly reduced and H2S significantly increased after CPAP in OSA patients with hypertension (p < 0.05) but not in OSA patients without hypertension (p > 0.05). CONCLUSION: Multivariate linear regression analysis demonstrated that 24h systolic BP and 24h diastolic BP correlated with H2S as well as their changes after CPAP treatment. Reduction in H2S may play a role in the pathogenesis of hypertension in patients with OSA.


Asunto(s)
Sulfuro de Hidrógeno/sangre , Hipertensión/sangre , Apnea Obstructiva del Sueño/sangre , Adulto , Anciano , Asociación , Presión Sanguínea/fisiología , Estudios de Casos y Controles , Presión de las Vías Aéreas Positiva Contínua , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/epidemiología , Hipertensión/terapia , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Polisomnografía , Factores de Riesgo , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/terapia
12.
Phys Chem Chem Phys ; 20(28): 19037-19044, 2018 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-29971283

RESUMEN

Three high-performance hydrazine sensing devices have been developed based on donor-acceptor perylenediimides (PDIs) with strongly electron-donating piperidinyl (PDI-PY), pyrrolidinyl (PDI-PI) and n-hexylamino (PDI-HE) as substituents at the perylene core. These PDI devices, compared with reported PDI molecules, displayed 1-2 orders of magnitude higher sensitivity, short response/recovery time and a lower detection limit towards hydrazine vapour. Experimental results demonstrated that PDI-HE possessed the most excellent sensing performance due to its larger electron density and well-defined crystalline structure with a smaller π-π distance of 3.55 Å, yet, poor crystalline structure, weak π-π orbital overlap as well as a larger interplanar spacing of 3.62 Å led to the poorest sensing performance of PDI-PY devices. This study clearly reveals that electron-donating substituents can remarkably improve the sensing performance of PDI devices by increasing the density of electrons, meanwhile, the steric hindrance of electron-donating groups can modulate the sensing performance by influencing the crystalline structure, π-π overlap and π-π distance. The excellent sensing performance makes donor-acceptor perylenes one of the candidates with the most potential for fabrication of highly efficient PDI sensing devices.

13.
Soft Matter ; 10(40): 7920-4, 2014 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-25228101

RESUMEN

Here we have shown that it is possible to modulate π-π stacking, hydrogen bonds and hydrophobic and hydrophilic interactions to further adjust the supramolecular helicity by simply changing the core-substituted group. These modulated supramolecular interactions provide a new pathway to the controlled production of helical superstructures.

14.
Adv Healthc Mater ; 13(11): e2303837, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38183408

RESUMEN

Targeted reprogramming of cancer-associated fibroblasts (CAFs) is one of the most essential cancer therapies. However, how to reprogram active CAFs toward deactivated state still remains immense challenge. To tackle this challenge, herein, one perylene N, N'-bis(2-((dimethylammonium)ethylene)-2-(methoxylethyl))-1, 6, 7, 12-tetrachloroperylene-3, 4, 9, 10-tetracarboxylic diimide (PDIC-OC) is prepared, which can trigger endogenous reactive oxygen species (ROS) burst to result in cytoskeletal dysfunction and cell apoptosis so that suppress transforming growth factor ß (TGF-ß) production. As a result, PDIC-OC can reprogram the activated CAFs and relieve immunosuppressive tumor microenvironment by efficient polarization of M2-typed macrophages into M1-typed ones, downregulation of alpha-smooth muscle actin (α-SMA), alleviation of hypoxic state to promote infiltration of cytotoxic T lymphocytes, and ultimately realizes outstanding antitumor performance on B16F10 tumor-xenografted and lung-metastatic mouse model even at low concentration of 1 mg kg-1 body weight. This work thus presents a novel strategy that cytoskeleton dysfunction and cell apoptosis cooperatively suppress the secretion of TGF-ß to reprogram CAFs and meanwhile clarifies intrinsic mechanism for perylene-triggered chemo-immunotherapy against hypoxic tumors.


Asunto(s)
Fibroblastos Asociados al Cáncer , Citoesqueleto , Inmunoterapia , Perileno , Animales , Perileno/análogos & derivados , Perileno/farmacología , Perileno/química , Ratones , Citoesqueleto/metabolismo , Citoesqueleto/efectos de los fármacos , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/efectos de los fármacos , Fibroblastos Asociados al Cáncer/patología , Inmunoterapia/métodos , Línea Celular Tumoral , Microambiente Tumoral/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismo , Apoptosis/efectos de los fármacos , Humanos , Especies Reactivas de Oxígeno/metabolismo , Ratones Endogámicos C57BL
15.
BMJ Open ; 14(2): e075257, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38418236

RESUMEN

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are prevalent respiratory diseases in China and impose significant burdens on the healthcare system. Moreover, the co-occurrence of COPD and OSA exacerbates clinical outcomes significantly. However, comprehensive epidemiological investigations in China remain scarce, and the defining characteristics of the population affected by COPD and OSA, alongside their intrinsic relationship, remain ambiguous. METHODS AND ANALYSIS: We present a protocol for a prospective, multicentre, observational cohort study based on a digital health management platform across three different healthcare tiers in five sites among Chinese patients with COPD. The study aims to establish predicative models to identify OSA among patients with COPD and to predict the prognosis of overlap syndrome (OS) and acute exacerbations of COPD through the Internet of Things (IoT). Moreover, it aims to evaluate the feasibility, effectiveness and cost-effectiveness of IoT in managing chronic diseases within clinical settings. Participants will undergo baseline assessment, physical examination and nocturnal oxygen saturation measuring. Specific questionnaires screening for OSA will also be administered. Diagnostic lung function tests and polysomnography will be performed to confirm COPD and OSA, respectively. All patients will undergo scheduled follow-ups for 12 months to record the changes in symptoms, lung functions and quality of life. Primary outcomes include the prevalence and characteristics of OS, while secondary outcomes encompass OS prognosis and the feasibility of the management model in clinical contexts. A total of 682 patients with COPD will be recruited over 12-24 months. ETHICS AND DISSEMINATION: The study has been approved by Peking University Third Hospital, and all study participants will provide written informed consent. Study results will be published in an appropriate journal and presented at national and international conferences, as well as relevant social media and various stakeholder engagement activities. TRIAL REGISTRATION NUMBER: NCT04833725.


Asunto(s)
Internet de las Cosas , Enfermedad Pulmonar Obstructiva Crónica , Apnea Obstructiva del Sueño , Humanos , Estudios Prospectivos , Calidad de Vida , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Atención a la Salud , Estudios de Cohortes , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/complicaciones , Estudios Observacionales como Asunto , Estudios Multicéntricos como Asunto
16.
Front Neurol ; 14: 1218334, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37483449

RESUMEN

Purpose: To systematically review the different types of irrigation fluid and the different temperatures of irrigation fluid on postoperative recurrence rates in the evacuation of chronic subdural hematoma (CSDH). Methods: We conducted a comprehensive search of electronic databases, including PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure (CNKI), WanFang, the Chinese VIP Information (VIP), and China Biology Medicine (CBM), and reference lists of relevant studies to identify all eligible studies. Two reviewers independently screened the titles and abstracts for inclusion, and the full-text articles were assessed for eligibility based on predetermined inclusion and exclusion criteria. Data were extracted using a standardized form, and the quality of the studies was assessed using a risk of bias tool. Meta-analyses were performed using a fixed-or random-effects model, and heterogeneity was assessed using the I2 statistic. The primary endpoint was the postoperative recurrence rate. Results: After stringent screening, a total of 11 studies were identified, including six English publications, four Chinese publications, and one Japanese publication, involving a population of 29,846 patients. Our meta-analysis provides evidence that artificial cerebrospinal fluid (ACF) could decrease the post-operative recurrence rate by 47% after the evacuation of CSDH when compared to normal saline (NS) [(odds ratio) OR 0.53, 95% confidence intervals (CI): 0.31-0.90, p = 0.02, I2 = 67%]. Besides, the irrigation fluid at body temperature could decrease the postoperative recurrence rate of CSDH by 64% when compared to room temperature (OR = 0.36, 95% CI = 0.22-0.59, p < 0.0001, I2 = 0%). Conclusion: Our analysis revealed significant difference in the choice of irrigation fluid for CSDH surgery. Notably, we found that irrigation with fluid at body temperature demonstrated superiority over irrigation with fluid at room temperature, resulting in fewer instances of recurrence. This straightforward technique is both safe and widely available, providing an opportunity to optimize outcomes for patients with CSDH. Our findings suggest that the use of body-temperature NS or ACF of room temperature during operation should be considered a standard of procedure in CSDH surgery. Nevertheless, whether the different temperature of ACF could be considered a standard of procedure in CSDH surgery still need high-quality RCTs to further identify. Systematic review registration: https://www.crd.york.ac.uk/prospero/; Identifier CRD42023424344.

17.
Front Neurol ; 14: 1219863, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38073650

RESUMEN

Background: Stroke represents a prominent global health issue, exhibiting the third highest incidence of disability and a significant burden on both healthcare and the economy. Stress hyperglycemia, an acute reaction of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, leading to adverse outcomes and mortality. Several previous studies have indicated that stress hyperglycemia, as evaluated by the stress hyperglycemia ratio (SHR), significantly increases the risk of adverse outcomes and mortality in stroke patients. However, there is a lack of further investigation into the influence of dynamic changes in stress hyperglycemia on the clinical outcomes of acute ischemic stroke (AIS) patients. Consequently, we performed a meticulous analysis, considering dose-response relationships from existing studies, to ascertain the correlation between dynamic changes in stress hyperglycemia and the susceptibility to adverse outcomes in patients with AIS. Methods: This investigation was prospectively registered in PROSPERO and adhered to the PRISMA guidelines. A comprehensive search was performed across English and Chinese databases. A two-sided random-effects model was employed to consolidate the odds ratios (ORs) of the highest vs. lowest categories of SHR. Restricted cubic spline (RCS) models were employed to estimate potential non-linear trends between SHR and the risk of adverse outcomes in AIS patients. Egger's test was utilized to assess publication bias. Heterogeneity was evaluated using Cochran's Q-test. The Newcastle-Ottawa Scale (NOS) tool was employed to evaluate the risk of bias of the included studies. Results: The final analysis incorporated a total of thirteen studies, which were published between 2019 and 2023, encompassing a participant cohort of 184,179 individuals. The SHR exhibited a significant association with the risk of various adverse outcomes. Specifically, a higher SHR was correlated with a 2.64-fold increased risk of 3-month poor functional outcomes (OR: 2.64, 95% CI 2.05-3.41, I2 = 52.3%, P < 0.001), a 3.11-fold increased risk of 3-month mortality (OR: 3.11, 95% CI 2.10-4.59, I2 = 38.6%, P < 0.001), a 2.80-fold increased risk of 1-year mortality (OR: 2.80, 95% CI 1.81-4.31, I2 = 88%, P < 0.001), a 3.90-fold increased risk of intracerebral hemorrhage (ICH) and 4.57-fold increased risk of symptomatic ICH (sICH) (ICH-OR: 3.90, 95% CI 1.52-10.02, I2 = 84.3%, P = 0.005; sICH-OR: 4.57, 95% CI 2.05-10.10, I2 = 47.3%, P < 0.001), a 1.73-fold increased risk of neurological deficits (OR: 1.73, 95 CI 1.44-2.08, I2 = 0%, P < 0.001), and a 2.84-fold increased risk of stroke recurrence (OR: 2.84, 95 CI 1.48-5.45, I2 = 50.3%, P = 0.002). It is noteworthy that, except for hemorrhagic transformation (HT) and stroke recurrence, the remaining adverse outcomes exhibited a "J-shaped" non-linear dose-response relationship. Conclusion: In summary, our findings collectively suggest that increased exposure to elevated SHR is robustly linked to a heightened risk of adverse outcomes and mortality in individuals with AIS, exhibiting a non-linear dose-response relationship. These results underscore the significance of SHR as a predictive factor for stroke prognosis. Therefore, further investigations are warranted to explore the role of SHR in relation to adverse outcomes in stroke patients from diverse ethnic populations. Furthermore, there is a need to explore the potential benefits of stress hyperglycemia control in alleviating the physical health burdens associated with AIS. Maintaining a lower SHR level may potentially reduce the risk of adverse stroke outcomes. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42023424852.

18.
Front Neurol ; 14: 1176390, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37181553

RESUMEN

Introduction: Stroke is a major global health concern and is ranked as the second leading cause of death worldwide, with the third highest incidence of disability. Intracerebral hemorrhage (ICH) is a devastating form of stroke that is responsible for a significant proportion of stroke-related morbidity and mortality worldwide. Hematoma expansion (HE), which occurs in up to one-third of ICH patients, is a strong predictor of poor prognosis and can be potentially preventable if high-risk patients are identified early. In this review, we provide a comprehensive summary of previous research in this area and highlight the potential use of imaging markers for future research studies. Recent advances: Imaging markers have been developed in recent years to aid in the early detection of HE and guide clinical decision-making. These markers have been found to be effective in predicting HE in ICH patients and include specific manifestations on Computed Tomography (CT) and CT Angiography (CTA), such as the spot sign, leakage sign, spot-tail sign, island sign, satellite sign, iodine sign, blend sign, swirl sign, black hole sign, and hypodensities. The use of imaging markers holds great promise for improving the management and outcomes of ICH patients. Conclusion: The management of ICH presents a significant challenge, and identifying high-risk patients for HE is crucial to improving outcomes. The use of imaging markers for HE prediction can aid in the rapid identification of such patients and may serve as potential targets for anti-HE therapies in the acute phase of ICH. Therefore, further research is needed to establish the reliability and validity of these markers in identifying high-risk patients and guiding appropriate treatment decisions.

19.
Front Immunol ; 14: 1235266, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37936706

RESUMEN

Background: Non-traumatic subarachnoid hemorrhage (SAH), primarily due to the rupture of intracranial aneurysms, contributes significantly to the global stroke population. A novel biomarker, pan-immune-inflammation value (PIV) or called the aggregate index of systemic inflammation (AISI), linked to progression-free survival and overall survival in non-small-cell lung cancer and mortality in Coronavirus Disease 2019 (COVID-19) patients, has surfaced recently. Its role in non-traumatic SAH patients, however, remains under-researched. This study aims to determine the relationship between PIV and all-cause mortality in non-traumatic SAH patients. Methods: A retrospective analysis was conducted using data from the Medical Information Mart for Intensive Care (MIMIC-IV) database to examine the association between PIV and all-cause mortality in critically ill patients with non-traumatic SAH. PIV measurements were collected at Intensive Care Unit (ICU) admission, and several mortality measures were examined. To control for potential confounding effects, a 1:1 propensity score matching (PSM) method was applied. The optimal PIV cutoff value was identified as 1362.45 using X-tile software that is often used to calculate the optimal cut-off values in survival analysis and continuous data of medical or epidemiological research. The relationship between PIV and short- and long-term all-cause mortality was analyzed using a multivariate Cox proportional hazard regression model and Kaplan-Meier (K-M) survival curve analysis. Interaction and subgroup analyses were also carried out. Results: The study included 774 non-traumatic SAH patients. After PSM, 241 pairs of score-matched patients were generated. The Cox proportional hazard model, adjusted for potential confounders, found a high PIV (≥ 1362.45) independently associated with 90-day all-cause mortality both pre- (hazard ratio [HR]: 1.67; 95% confidence intervals (CI): 1.05-2.65; P = 0.030) and post-PSM (HR: 1.58; 95% CI: 1.14-2.67; P = 0.042). K-M survival curves revealed lower 90-day survival rates in patients with PIV ≥ 1362.45 before (31.1% vs. 16.1%%, P < 0.001) and after PSM (68.9% vs. 80.9%, P < 0.001). Similarly, elevated PIV were associated with increased risk of ICU (pre-PSM: HR: 2.10; 95% CI: 1.12-3.95; P = 0.02; post-PSM: HR: 2.33; 95% CI: 1.11-4.91; P = 0.016), in-hospital (pre-PSM: HR: 1.91; 95% CI: 1.12-3.26; P = 0.018; post-PSM: 2.06; 95% CI: 1.10-3.84; P = 0.034), 30-day (pre-PSM: HR: 1.69; 95% CI: 1.01-2.82; P = 0.045; post-PSM: 1.66; 95% CI: 1.11-2.97; P = 0.047), and 1-year (pre-PSM: HR: 1.58; 95% CI: 1.04-2.40; P = 0.032; post-PSM: 1.56; 95% CI: 1.10-2.53; P = 0.044) all-cause mortality. The K-M survival curves confirmed lower survival rates in patients with higher PIV both pre- and post PSM for ICU (pre-PSM: 18.3% vs. 8.4%, P < 0.001; post-PSM:81.7 vs. 91.3%, P < 0.001), in-hospital (pre-PSM: 25.3% vs. 12.8%, P < 0.001; post-PSM: 75.1 vs. 88.0%, P < 0.001), 30-day (pre-PSM: 24.9% vs. 11.4%, P < 0.001; post-PSM:74.7 vs. 86.3%, P < 0.001), and 1-year (pre-PSM: 36.9% vs. 20.8%, P < 0.001; P = 0.02; post-PSM: 63.1 vs. 75.1%, P < 0.001) all-cause mortality. Stratified analyses indicated that the relationship between PIV and all-cause mortality varied across different subgroups. Conclusion: In critically ill patients suffering from non-traumatic SAH, an elevated PIV upon admission correlated with a rise in all-cause mortality at various stages, including ICU, in-hospital, the 30-day, 90-day, and 1-year mortality, solidifying its position as an independent mortality risk determinant. This study represents an attempt to bridge the current knowledge gap and to provide a more nuanced understanding of the role of inflammation-based biomarkers in non-traumatic SAH. Nevertheless, to endorse the predictive value of PIV for prognosticating outcomes in non-traumatic SAH patients, additional prospective case-control studies are deemed necessary.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Hemorragia Subaracnoidea , Humanos , Estudios Retrospectivos , Enfermedad Crítica , Inflamación
20.
Adv Sci (Weinh) ; 10(3): e2204498, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36373677

RESUMEN

Perylene derivatives can be stimulated by the hypoxic tumor microenvironment to generate radical anion that is proposed to arouse electron exchange with oxidizing substance, and in turn, realize reactive oxygen species (ROS) burst. Here, three perylene therapeutic agents, PDI-NI, PDIB-NI, and PDIC-NI, are developed and it is found that the minimum lowest unoccupied molecular orbital (LUMO) energy level makes PDIC-NI most easily accept electrons from the oxidative respiratory chain to form lots of anions, and the resultant maximum ROS generation, establishing an unambiguous mechanism for the formation of perylene radical anions in the cell, presents solid evidence for LUMO energy level determining endogenous ROS burst. Stirringly, PDIC-NI-induced ROS generation arouses enhanced mitochondrial oxidative stress and concurrently activates immunogenic cell death (ICD), which not only efficiently kills lung tumor cells but also reprograms immunosuppressive tumor microenvironment, including the cytokine secretion, dendritic cell maturation, as well as cytotoxic T lymphocytes activation, to inhibit the growth of xenografted and metastasis tumor, presenting a proof-of-concept demonstration of perylene that acts as an integrated therapeutic agent to well realize hypoxia-activated chemotherapy with ICD-induced immunotherapy on lung cancer.


Asunto(s)
Neoplasias , Perileno , Humanos , Especies Reactivas de Oxígeno/metabolismo , Transporte de Electrón , Perileno/farmacología , Perileno/uso terapéutico , Electrones , Neoplasias/terapia , Hipoxia , Inmunoterapia , Microambiente Tumoral
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